Culture

WASHINGTON, September 8, 2020 -- Inspired by the need for new and better therapies for neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, Rutgers University researchers are exploring the link between uncontrolled inflammation within the brain and the brain's immune cells, known as microglia.

Most therapies for brain health disorders focus on the major cells of the nervous system: neurons. But microglia cells are emerging as a promising cellular target because of the prominent role they play in brain inflammation. In addition, microglial behavior can be engineered to rein in inflammation, which is caused by different factors, and the damage it causes.

In APL Bioengineering, from AIP Publishing, the group highlights the design considerations and benefits of creating therapeutic nanoparticles for carrying pharmacological factors directly to the sites of the microglia.

Microglia are essentially first responders to pathological changes within the brain and can readily clear out undesired and foreign substances.

"Emerging drugs and biological factors can be targeted and released in controlled ways within the brain if their nanoscale carriers can be engineered," said Prabhas V. Moghe, co-author on the paper. "We believe this field is ripe for technological, biological, and clinical breakthroughs."

The group's ultimate goal is to tamp down the uncontrolled activation of microglial inflammation.

"Within our lab at Rutgers, we are developing a new therapeutic strategy targeted to the microglia activated by the excessive deposition of the protein alpha-synuclein," Moghe said. "This will potentially address a major therapeutic barrier of microglial activation in neurodegenerative diseases."

Targeting microglia in this manner may open up avenues for the development of novel therapeutics.

"Studying nanoparticle interactions with microglia can guide the design of successful nanomedicine platforms that enable targeted delivery of drugs while minimizing off-target effects and system-level toxicity," Moghe said. "Considering the complex nature of neurodegenerative disorders, rather than solely focusing on therapies for neurons, it may be worth directing therapeutics to the mediator, microglia, whose functional restoration will protect neurons."

Scientists from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago were the first to examine endothelial cells - one of the main sources of blood production - for clues as to why people with Down syndrome have higher prevalence of leukemia. They identified a new set of genes that are overexpressed in endothelial cells of patients with Down syndrome. This creates an environment conducive to leukemia, which is characterized by uncontrolled development and growth of blood cells. Their findings, published in the journal Oncotarget, point to new potential targets for treatment and possibly prevention of leukemia, in people with Down syndrome and in the general population.

"We found that Down syndrome, or Trisomy 21, has genome-wide implications that place these individuals at higher risk for leukemia," says co-lead author Mariana Perepitchka, BA, Research Associate at the Manne Research Institute at Lurie Children's. "We discovered an increased expression of leukemia-promoting genes and decreased expression of genes involved in reducing inflammation. These genes were not located on chromosome 21, which makes them potential therapeutic targets for leukemia even for people without Down syndrome."

Down syndrome is a congenital genetic disorder caused by additional genetic material from an extra copy of chromosome 21. The condition occurs in about one in 700 babies. In addition to developmental and physical impairments, people with Down syndrome have a 500-fold risk of developing acute megakaryoblastic leukemia (AMKL) and a 20-fold risk of being diagnosed with acute lymphoblastic leukemia (ALL).

"Our discovery of leukemia-conducive gene expression in endothelial cells could open new avenues for cancer research," says co-lead author Yekaterina Galat, BS, Research Associate at the Manne Research Institute at Lurie Children's.

The study used skin samples from patients with Down syndrome to create induced pluripotent stem cells (iPSC) that were then differentiated into endothelial cells. Impairment in endothelial cell genetic expression was found to produce altered endothelial function throughout the cell maturation.

"Fortunately, advances in iPSC technology have provided us with an opportunity to study cell types, such as endothelial cells, that are not easily attainable from patients," says senior author Vasil Galat, PhD, Director of Human iPS and Stem Cell Core at Manne Research Institute at Lurie Children's and Research Assistant Professor of Pathology at Northwestern University Feinberg School of Medicine. "If our results are confirmed, we may have new gene targets for developing novel leukemia treatments and prevention."

What The Study Did: Clinical features of COVID-19 are compared in this observational study with those of influenza A and B in U.S. children.

Authors: Xiaoyan Song, Ph.D, M.B.B.S., of the Children's National Hospital  in Washington, D.C., is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.20495)

Editor's Note:  Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

As the fall approaches, pediatric hospitals will start seeing children with seasonal influenza A and B. At the same time, COVID-19 will be co-circulating in communities with the flu and other respiratory viruses, making it more difficult to identify and prevent the novel coronavirus.

With little published data directly comparing the clinical features of children with COVID-19 to those with seasonal flu, researchers at Children's National Hospital decided to conduct a retrospective cohort study of patients in the two groups. Their findings -- published September 8 in JAMA Network Open -- surprised them.

The study -- detailed in the article "Comparison of Clinical Features of US Children With COVID-19 vs Seasonal Influenza A and B" -- showed no statistically significant differences in the rates of hospitalization, admission to the intensive care unit and mechanical ventilator use between the two groups.

The other unexpected finding was that more patients with COVID-19 than those with seasonal influenza reported fever, cough, diarrhea or vomiting, headache, body ache or chest pain at the time of diagnosis, says Xiaoyan Song, Ph.D., M.Sc., M.B., the study's principal investigator.

"I didn't see this coming when I was thinking about doing the study," says Dr. Song, director of Infection Control and Epidemiology at Children's National since 2007 and a professor of pediatrics at the George Washington University School of Medicine and Health Sciences. "It took several rounds of thinking and combing through the data to convince myself that this was the conclusion."

Given that much remains unknown about COVID-19, the researchers' discovery that children with the disease present with more symptoms at the time of diagnosis is a valuable one.

"It's a good cue from a prevention and planning perspective," says Dr. Song. "We always emphasize early recognition and early isolation with COVID. Having a clinical picture in mind will assist clinicians as they diagnose patients with symptoms of the coronavirus."

The study included 315 children who were diagnosed with a laboratory-confirmed COVID-19 between March 25, 2020, and May 15, 2020, and 1,402 children who were diagnosed with a laboratory-confirmed seasonal influenza between Oct. 1, 2019, and June 6, 2020, at Children's National. Asymptomatic patients who tested positive for COVID-19 during pre-admission or pre-procedural screening were excluded from the study.

Of the 315 patients who tested positive for COVID-19, 52% were male, with a median age of 8.4 years. Of these patients, 54 (17.1 %) were hospitalized, including 18 (5.7%) who were admitted to the intensive care unit (ICU) and 10 (3.2%) who received mechanical ventilator treatment.

Among the 1,402 patients who tested positive for influenza A or B, 52% were male, with a median age of 3.9 years, and 291 (21.2%) were hospitalized, including 143 for influenza A and 148 for influenza B. Ninety-eight patients (7.0%) were admitted to the ICU, and 27 (1.9%) received mechanical ventilator support.

The study showed a slight difference in the age of children hospitalized with COVID-19 compared to those hospitalized with seasonal influenza. Patients hospitalized with COVID-19 had a median age of 9.7 years vs. those hospitalized with seasonal influenza who had a median age of 4.2 years.

In both groups, fever was the most often reported symptom at the time of diagnosis followed by cough. A greater proportion of patients hospitalized with COVID-19 than those hospitalized with seasonal influenza reported fever (76% vs. 55%), cough (48% vs. 31%), diarrhea or vomiting (26% vs. 12%), headache (11% vs. 3%), body ache/myalgia (22% vs. 7%), and chest pain (11% vs. 3%).

More patients hospitalized with COVID-19 than those with seasonal influenza reported sore throat or congestion (22% vs. 20%) and shortness of breath (30% vs. 20%), but the differences were not statistically significant.

During the study period, the researchers noticed an abrupt decline of influenza cases at Children's National after local schools closed in mid-March and stay-at-home orders were implemented about two weeks later to combat the community spread of COVID-19. Dr. Song says the impact of school closures on the spread of COVID-19 among children is the next area of study for her research team.

"We want to assess the quantitative impact of school closures so we can determine at what point the cost of closing schools and staying at home outweighs the benefit of reducing transmission of COVID-19 and burdens on the health care system," she says.

Dr. Song urges members of the community "first and foremost to stay calm and be strong. We're learning new and valuable things about this virus each day, which in turn improves care. The collision of the flu and COVID-19 this fall could mean an increase in pediatric hospitalizations. That's why it's important to get your flu shot, because it can help take at least one respiratory virus out of circulation."

What The Study Did: Anonymous mobile phone location data were used to examine travel and home dwelling time patterns before and after enactment of stay-at-home orders in U.S. states to examine associations between changes in mobility and the COVID-19 curve.

Authors: Song Gao, Ph.D., and Jonathan A. Patz, M.D., of the University of Wisconsin in Madison, are the corresponding authors.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.20485)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Parents might be familiar with their toddlers gotten messy with flour. Feeling the soft texture of flour, kids can spend the whole time and create, explore and learn through the messy play. Such tactile sensory play is an effective stimulus for children's senses as the tactile system includes the entire network of skin. Thalamus in the brain is where general sensory inputs are filtered in and out, yet it has remained elusive as to what specific mechanism fine-tunes the sense of touch.

Led by Dr. C. Justin Lee at the Center for Cognition and Sociality within the Institute for Basic Science (IBS) in Daejeon, South Korea, and Dr. CHEONG Eunji at Yonsei University, the joint research team has revealed the production pathway of the sense of touch. They found that the persistent regulation (tonic) of γ-aminobutyric acid (GABA), which is the main inhibitory transmitter in the astrocytes (star-shaped cells), generates the sense of touch. "Contrary to the conventional assumption, thalamic astrocytes were found to synthesize GABA using an enzyme called diamine oxidase (DAO), rather than MAOB, previously known as a GABA-producing enzyme in cerebellar astrocytes," says KOH Wuhyun, first author of the study. The research team also found that the production of GABA is completed by an enzyme called Aldh1a1. The team confirmed that the GABA produced is released through Best1 channel in astrocytes. They also experimentally proved that astrocytic tonic GABA in the thalamus controls our brain's acuity to make sense of touch.

The study reports a rather surprise finding as to how GABA works to control the tactile sense. GABA, known for its inhibitory function, actually enhances the sensory input processing by accelerating the signal processing and sharpening the sensitivity of signal magnitude. "The brain cannot accurately distinguish saturated neuronal signals. It is like that too much exposure to light results in an overly bright photo. GABA's inhibitory action removes extreme values of signals and accentuates the information of each signal. This fine-tuning helps neurons to be more sensible to various range of signals," explains Koh.

In behavioral experiments, the research team verified that tonic GABA dynamically controls tactile discrimination. They used sandpaper with various grits; the smaller the grit number the more coarse the particles, the larger the number the more fine. Its tactile-based novel object recognition test showed that astrocytic knockdown models of Best1, DAO, and Aldh1a1 reported a significantly lower discrimination ability compared to the control group. The team also confirmed the effect of enhancement of tonic GABA: Overly-charged models demonstrated a greatly enhanced ability of discrimination. They were able to notify relatively small change of textile, (?80). Normal models usually recognize a difference of ?180 or more.

Co-corresponding author, Dr. CHEONG Eunji states, "Detecting a small change of the surroundings marks the beginning of our cognitive function. This study uncovered a novel mechanism of manipulating sensory acuity, offering a breakthrough for the study of sensory and cognitive functions."

"This is the first example of how the astrocytes in the thalamus actively participate in important cognitive processes, such as sensory discrimination. Astrocytes "shine" in the brain to actively engage in cognitive functions, just as the stars in the night sky." notes Dr. C. Justin Lee, co-corresponding author.

One of the biggest scientific advances of the last decade is getting better thanks to researchers at The University of Texas at Austin; the University of California, Berkeley; and Korea University. The team has developed a new tool to help scientists choose the best available gene-editing option for a given job, making the technology called CRISPR safer, cheaper and more efficient. The tool is outlined in a paper out today in Nature Biotechnology.

The CRISPR gene-editing technique holds tremendous potential to improve human health, agriculture and the future of people on the planet, but the challenge lies in the delicate nature of gene editing -- there is almost no room for error.

To edit genes, scientists use dozens of different enzymes from a naturally occurring system called CRISPR. Researchers locate a problematic DNA sequence and use these specialized enzymes to snip it as if using a pair of scissors, allowing genetic material to be added, removed or altered. But these scissors are not perfect. Accuracy and effectiveness vary by the CRISPR enzyme and the project. The new tool guides users, so they can pick the best CRISPR enzyme for their high-stakes gene edit.

"We designed a new method that tests the specificity of these different CRISPR enzymes -- how precise they are -- robustly against any changes to the DNA sequence that could misdirect them, and in a cleaner way than has ever been done before," said Steve Jones, a UT research scientist who co-wrote the paper with Ilya Finkelstein, an associate professor of molecular biosciences.

Problems can occur when a CRISPR enzyme targets the wrong sections of DNA. Each CRISPR enzyme has strengths and weaknesses in editing different sequences, so the researchers set out to create a tool to help scientists compare the different enzymes and find the best one for a given job.

"CRISPR wasn't designed in a lab. It wasn't made by humans for humans. It was made by bacteria to defend against viruses," said John Hawkins, a Ph.D. alumnus who was recently with UT's Oden Institute for Computational Engineering and Sciences. "There is incredible potential for its use in medicine, but the first rule of medicine is 'do no harm.' Our work is trying to make CRISPR safer."

The team of researchers developed a library of DNA sequences and measured how accurate each CRISPR enzyme was, how long it took the enzyme to edit the sequences and how precisely they edited the sequence. For some tasks the commonly used enzyme CRISPR-Cas9 worked best; in others, different enzymes performed much better.

"It's like a standardized test," Hawkins said. "Every student gets the same test, and now you have a benchmark to compare them."

The tool allows scientists to choose the best enzyme for editing on the first try, so the process becomes more efficient and cheaper. Additionally, it gives scientists information about where mistakes are most likely to occur for each enzyme, saving time.

"This technique gives us a new way to reduce risk," Jones said. "It allows gene edits to be more predictable."

A global analysis reveals for the first time that across almost all tree species, fast growing trees have shorter lifespans. This international study further calls into question predictions that greater tree growth means greater carbon storage in forests in the long term.

Currently, forests absorb large amounts of carbon dioxide (CO2) from the atmosphere. This is thought to be due to higher temperatures and abundant CO2 stimulating growth in trees, allowing them to absorb more CO2 as they grow.

Most earth system models predict that this growth stimulation will continue to cause a net carbon uptake of forests this century. But, the study, led by the University of Leeds and published today in Nature Communications, casts doubts on these predictions.

The international study is the largest to date looking at the relationship between tree growth and tree lifespan. The researchers examined more than 200 thousand tree-ring records from 82 tree species from sites across the globe.

It confirms that accelerated growth results in shorter tree lifespans, and that growth-lifespan trade-offs are indeed near universal, occurring across almost all tree species and climates.
This suggests that increases in forest carbon stocks may be short lived.

Lead author of the study, Dr Roel Brienen from the School of Geography at Leeds, said: "While it has been known for a long time that fast-growing trees live shorter, so far this was only shown for a few species and at a few sites.

"We started a global analysis and were surprised to find that these trade-offs are incredibly common. It occurred in almost all species we looked at, including tropical trees.

"Our modelling results suggest there is likely to be a time lag before we see the worst of the potential loss of carbon stocks from increases in tree mortality. They estimate that global increases in tree death don't kick in until after sites show accelerated growth.

"This is consistent with observations of increased tree death trends across the globe. For example, previous Leeds research has shown long-term increases in tree mortality rates lagging behind tree growth increases in the Amazon forest."

Co-author Prof Manuel Gloor, also from the School of Geography, said: "Earth system models often do not, or cannot by design, take into account this negative feedback, and model projections of the global forest carbon sink persistence are thus likely inaccurate and too optimistic. Our findings imply that a much reduced future forest carbon sink further increases the urgency to curb greenhouse emissions."

The trade-off may be due to environmental variables affecting tree growth and lifespan. For example, co-author, Dr Alfredo Di Filippo from Tuscia University, Italy previously reported that lifespan of beech trees in the Northern Hemisphere decreases by roughly 30 years for each degree of warming.

The current analysis confirms that, across biomes, reductions in lifespan are not due directly to temperature per se, but are a result of faster growth at warmer temperatures.

Their findings suggests that a prominent cause of the widespread occurrence of a growth lifespan trade-off is that chances of dying increase dramatically as trees reach their maximum potential tree size.

Nonetheless, other factors may still play a role as well. For example, trees that grow fast may invest less in defences against diseases or insect attacks, and may make wood of lower density or with water transport systems more vulnerable to drought.

Study co-author Dr Steve Voelker, from the Department of Environmental and Forest Biology, Syracuse, New York, said: "Our findings, very much like the story of the tortoise and the hare, indicate that there are traits within the fastest growing trees that make them vulnerable, whereas slower growing trees have traits that allow them to persist.

"Our society has benefitted in recent decades from the ability of forests to increasingly store carbon and reduce the rate at which CO2 has accumulated in our atmosphere. However, carbon uptake rates of forests are likely to be on the wane as slow-growing and persistent trees are supplanted by fast-growing but vulnerable trees."

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."