Tech

The prevalence of SARS-CoV-2 infections in preschool and school children is an important benchmark for deciding whether to open kindergartens and schools. The screening study "Fr1da" led by Anette-Gabriele Ziegler tests children in Bavaria for an early stage of type 1 diabetes. These tests include the collection of blood samples. In response to the COVID-19 pandemic, the researchers had decided to use the valuable study infrastructure of the Fr1da study to detect SARS-CoV-2 infections, too. For this, they developed a SARS-CoV-2 antibody test with particularly high accuracy. During the first wave in Germany in spring 2020, the researchers detected a SARS-CoV-2 antibody frequency of 0.87 percent in the children who took part in the Fr1da study. This means that six times more children in Bavaria were infected with the coronavirus than reported via PCR tests (link to press release).

More infections during the second wave in Germany

While the Fr1da study continued, the researchers found a significant increase of SARS-CoV-2 antibodies in children in Bavaria during the second wave in autumn and winter. Preschool children showed an antibody frequency of 5.6 percent during the testing period October 2020 to February 2021. Among school children who were tested between November 2020 and February 2021, the figure was as high as 8.4 percent. Overall, the antibody frequency at the end of the second wave (January and February 2021) was about eight times higher compared to the end of the first wave (April to July 2020). In addition, results showed that three to four times more preschool and school children in Bavaria were infected with SARS-CoV-2 than reported via PCR testing during the second wave.

Many children are asymptomatic

Markus Hippich, first author of the study and researcher at Helmholtz Zentrum München, says: "The fact that we found more infections in children compared to reported cases may be due to asymptomatic cases in childhood." Among the 446 children who tested positive in the second wave, 92.6 percent completed symptom questionnaires. The proportion of antibody-positive children without symptoms was 68.0 percent among preschoolers. Among school-aged children, it was 51.2 percent.

The researchers suggest that the significant increase in SARS-CoV-2 infections during the second wave is the result of a combination of events. These include a generally higher exposure to the virus in the fall and winter, school openings and novel, more infectious virus variants. Study leader Anette-Gabriele Ziegler explains: "Children are often said to be less likely infected compared to adults. However, the data for this assumption is sparse. The results of our study clearly show that both preschool and school children are susceptible to SARS-CoV-2 infection. To better control infections in this population group, adequate measures to contain the spread of the virus in kindergartens and schools could be helpful."

Antibodies can be detected over several months

Children who tested positive for SARS-CoV-2 antibodies had the possibility to provide another blood sample to check the development of their antibody status. The researchers observed that the titer of antibodies increased over a period of average three months after the first sample. Overall, 64 of 66 children remained positive for SARS-CoV-2 antibodies. The researchers expect that the antibody increase is not due to re-exposure, but rather the natural time course of antibody responses.

No association between type 1 diabetes and COVID-19 in children

The Fr1da study screens children in Bavaria up to the age of 10 years for pre-symptomatic type 1 diabetes defined by the presence of multiple islet autoantibodies. The researchers did not find an association between pre-symptomatic type 1 diabetes (positive test for islet autoantibodies) and COVID-19 (positive test for SARS-CoV-2 antibodies), neither during the first nor the second wave.

How can large amounts of data be transferred or processed as quickly as possible? One key to this could be graphene. The ultra-thin material is only one atomic layer thick, and the electrons it contains have very special properties due to quantum effects. It could therefore be very well suited for use in high-performance electronic components. Up to this point, however, there has been a lack of knowledge about how to suitably control certain properties of graphene. A new study by a team of scientists from Bielefeld and Berlin, together with researchers from other research institutes in Germany and Spain, is changing this. The team's findings have been published in the journal Science Advances.

Consisting of carbon atoms, graphene is a material just one atom thick where the atoms are arranged in a hexagonal lattice. This arrangement of atoms is what results in graphene's unique property: the electrons in this material move as if they did not have mass. This "massless" behavior of electrons leads to very high electrical conductivity in graphene and, importantly, this property is maintained at room temperature and under ambient conditions. Graphene is therefore potentially very interesting for modern electronics applications.

It was recently discovered that the high electronic conductivity and "massless" behavior of its electrons allows graphene to alter the frequency components of electric currents that pass through it. This property is highly dependent on how strong this current is. In modern electronics, such a nonlinearity comprises one of the most basic functionalities for switching and processing of electrical signals. What makes graphene unique is that its nonlinearity is by far the strongest of all electronic materials. Moreover, it works very well for exceptionally high electronic frequencies, extending into the technologically important terahertz (THz) range where most conventional electronic materials fail.

In their new study, the team of researchers from Germany and Spain demonstrated that graphene's nonlinearity can be very efficiently controlled by applying comparatively modest electrical voltages to the material. For this, the researchers manufactured a device resembling a transistor, where a control voltage could be applied to graphene via a set of electrical contacts. Then, ultrahigh-frequency THz signals were transmitted using the device: the transmission and subsequent transformation of these signals were then analyzed in relation to the voltage applied. The researchers found that graphene becomes almost perfectly transparent at a certain voltage - its normally strong nonlinear response nearly vanishes. By slightly increasing or lowering the voltage from this critical value, graphene can be turned into a strongly nonlinear material, significantly altering the strength and the frequency components of the transmitted and remitted THz electronic signals.

"This is a significant step forward towards implementation of graphene in electrical signal processing and signal modulation applications," says Prof. Dmitry Turchinovich, a physicist at Bielefeld University and one of the heads of this study. "Earlier we had already demonstrated that graphene is by far the most nonlinear functional material we know of. We also understand the physics behind nonlinearity, which is now known as thermodynamic picture of ultrafast electron transport in graphene. But until now we did not know how to control this nonlinearity, which was the missing link with respect to using graphene in everyday technologies."

"By applying the control voltage to graphene, we were able to alter the number of electrons in the material that can move freely when the electrical signal is applied to it," explains Dr. Hassan A. Hafez, a member of Professor Dr. Turchinovich's lab in Bielefeld, and one of the lead authors of the study. "On one hand, the more electrons can move in response to the applied electric field, the stronger the currents, which should enhance the nonlinearity. But on the other hand, the more free electrons are available, the stronger the interaction between them is, and this suppresses the nonlinearity. Here we demonstrated - both experimentally and theoretically - that by applying a relatively weak external voltage of only a few volts, the optimal conditions for the strongest THz nonlin-earity in graphene can be created."

"With this work, we have reached an important milestone on the path towards to using graphene as an extremely efficient nonlinear functional quantum material in devices like THz frequency converters, mixers, and modulators," says Professor Dr. Michael Gensch from the Institute of Optical Sensor Systems of the German Aerospace Center (DLR) and the Technical University of Berlin, who is the other head of this study. "This is extremely relevant because graphene is perfectly compatible with existing electronic ultrahigh-frequency semiconductor technology such as CMOS or Bi-CMOS. It is therefore now possible to envision hybrid devices in which the initial electric signal is generated at lower frequency using existing semiconductor technology but can then very efficiently be up-converted to much higher THz frequencies in graphene, all in a fully controllable and predictable manner."

Leesburg, VA, April 8, 2021--According to an open-access article in ARRS' American Journal of Roentgenology (AJR), IV contrast-enhanced 2-millisievert CT (2-mSv CT) is comparable to conventional-dose CT (CDCT) for the diagnosis of right colonic diverticulitis.

"By mitigating concern of missed diagnosis of right colonic diverticulitis, our results further support the use of low-dose CT for suspected appendicitis," wrote first author Hae Young Kim from the department of radiology at Korea's Seoul National University Bundang Hospital. "To our knowledge," Kim et al. maintained, "this is the first study to formally measure the diagnostic performance of CT for right colonic diverticulitis."

Kim and colleagues' large pragmatic randomized controlled trial data included 3,074 patients (1,672 women, 1,402 men) aged 15-44 years old (median, 28 years) from 20 hospitals, randomized into 2-mSv (n = 1,535) or CDCT (median, 7-mSv; n = 1,539) groups from December 2013 to August 2016. A total of 161 radiologists prospectively issued CT reports, suggesting alternative diagnoses in 976 (2-mSV CT) and 924 (CDCT) patients.

In the intention-to-treat analysis, the between-group differences were minute with narrow 95% confidence intervals for most endpoints related to right colonic diverticulitis: test-positives (0.2%; p = .93), test-negatives (0.5%; p = .67), sensitivity (0.0%; p > .99), and specificity (0.2%; p = .66). The characteristics and disposition of test-positive patients were similar between the two groups.

"We believe our results reflect what can be expected in real-word conditions, owing to the pragmatic nature of the trial design, whereby we tried to deliver the intervention with the actual resources used in daily clinical practice," the authors of this AJR article added.

Scientists of Tomsk Polytechnic University have created a decision support system (DSS) for dispatching personnel of electric power systems (EPS). The system allows dispatchers to quickly test their actions on the management of the EPS, to control and evaluate their consequences using a digital simulator in a regime faster than real time.

The article devoted to the research work is published in the IEEE Transactions on Power Systems (Q1, IF 6.074) academic journal, one of the most peer-reviewed journals in energy, energy technology, electrical engineering and electronics industries.

"An EPS is some kind of a living organism within that changes are permanently and continually taking place. In order this organism functionates properly and without any failures, it must be controlled. This extremely complicated task is carried out by dispatching personnel. Moreover, wrong or belated actions of a dispatcher can exacerbate an emergency," Aleksey Suvorov, Associate Professor of the TPU Division for Power and Electrical Engineering, one of the authors of the article, says.

He adds that the DSS is a continuation of the research work for a multiprocessor system for real-time simulation of the EPS. For this development, a research team of young scientists from the TPU Research Laboratory for Power Grid Simulation, including Mikhail Andreev, Nikolay Ruban, Aleksey Suvorov and Ruslan Ufa, was conferred with the Russian Federation Government Prize in Science and Technology for Young Scientists. The comprehensive simulation system allows obtaining a huge volume of information on the operation of the EPS. The data are kept on the server. The DSS operates with these data.

"A DSS has been created based on a hybrid approach to EPS simulation that was developed by Alexander Gusev, Professor of the TPU Division for Power and Electrical Engineering. Its core lies in the combination of existing simulation techniques (analog, physical and digital) and the use of the best properties and capabilities of each of the techniques. Using a DSS, methodically accurate simulation is implemented in real time of the EPS of any scale and complication. The system is actually an alternative to a real EPS, its digital simulator. Furthermore, due to the properties of a hybrid approach, a simulation capability faster than in real time implemented. On the current element base, it was possible to speed up by five folds. It allows the operator to test several case scenarios, to choose the most effective one, to adjust a regime state and only after that to act in a real EPS, reducing a possible negative effect from his actions," the scientist explains.

All components of the system, including special software, are developed at TPU. The system effectiveness was tested at a real EPS of the Tomsk Region.

"The DSS simultaneously operates with the EPS and collects data from the operative-information complex (OIC). The OIC monitors a regime of the EPS, collects the data about voltage, power and controls how the system operates. To test the system, we created a special emulator simulated the OIC. Using the emulator, an emergency visible for the dispatcher and the system was simulated. The DSS software contains all required algorithms and case scenarios. The dispatchers possess very strict regulatory directions regarding what actions must be taken in any situation. According to the occurred emergency, the DSS processes the incoming information and suggests patterns based on the direction. Besides, due to the fast simulation, the dispatcher possesses more time to control and take the rightest pattern," Aleksey Suvorov elaborates.

The effectiveness of the system operation was also experimentally tested jointly with scientists from the Indian Institutes of Technology (Roorkee).

Fabrication of 3D freeform structures of thermoplastics involving overhang (non-anchored) structures is successfully showcased by fused deposition modeling (FDM) and direct ink writing (DIW), yet limited in terms of applicable materials and conditions of printing. 3D printing of freeform structures requires support materials that enable printing of thermoplastics in non-anchored locations.

In order to address the difficulty of freeform fabrication via extrusion-based printing, the use of microparticulate gels as embedding media has been widely explored. Such methods are collectively termed embedded 3D printing (e3DP).

In these demonstrations, the gels behaved as Bingham plastics with a low modulus and low yield stress during the printing of low-viscosity resins. e3DP enabled the freeform fabrication of different materials such as silicones, hydrogels, casting alloys, colloids, and hydrogels containing living cells.

Despite all these successful studies, freeform fabrication of thermoplastics has not been demonstrated with e3DP. This is because the molten thermoplastics and the nozzles are typically greater than 100°C, and they are not compatible with the support media consisting of microparticulate hydrogels.

Researchers from the Singapore University of Technology and Design's (SUTD) Soft Fluidics Lab developed a simple method to 3D print thermoplastics using embedded media in freeform manners, termed freeform polymer precipitation (FPP).

In FPP, microparticulate gels as surrounding media simultaneously offered two essential functions. The microparticulate gels provided structural support to the printed ink and induced the phase change of the printed ink via immersion precipitation. 3D printing based on immersion precipitation with surrounding microparticulate has unlocked the capability of freeform fabrication of thermoplastics.

The study demonstrated the use of both water-based and ethanol-based microparticulate gels as surrounding gels that allowed the increased numbers of solvents and polymers to be used in FPP. Polymer inks with low polymer concentrations (with low viscosity) and inks with pore-inducing agents conferred internal porosity to the printed structures.

"Our approach has overcome the limitation of use of microparticulate media for the fabrication of freeform structures of thermoplastics, for the first time, using the immersion precipitation of polymer inks in microparticulate gels," said the lead author of the paper Dr Rahul Karyappa from SUTD.

"FPP offers a unique way to fabricate mechanically strong components consisting of thermoplastics in various 3D shapes without support materials. This expands the available technologies of additive manufacturing," added principal investigator, Associate Professor Michinao Hashimoto from SUTD.

Flamingo chicks raised by foster parents from another flamingo species develop normally, scientists say.

Six Chilean flamingo chicks were reared by Andean flamingos - a species of similar size and behaviour - at WWT Slimbridge Wetland Centre in the summer of 2018.

University of Exeter scientists studied the chicks' behaviour after they re-joined the Chilean flamingo flock early in 2019.

The results showed fostering had no negative effects, with fostered flamingos still forming stable social ties - making "friends" and behaving like parent-reared birds.

"Slimbridge's Andean flamingos hadn't nested for about 20 years," said Dr Paul Rose, of the University of Exeter.

"But in the hot summer of 2018 - probably due to the high temperatures - they made nests and laid eggs.

"Unfortunately, the eggs turned out to be infertile, possibly due to the age of the birds - some of them are approaching their 60s.

"To give them enrichment (allowing them to behave naturally), keepers placed six eggs from the Chilean flamingo flock to be raised by the Andean flamingos.

"This gave us a rare opportunity to study the effects of fostering - although it should be noted that these species are remarkably similar, and this would not have been attempted otherwise."

Peter Kidd, then a student on Exeter's MSc Animal Behaviour course, observed and recorded the chicks' behaviour from April to July 2019 (after their return to their own flock).

These observations were used to study integration and social networks.

"The six fostered chicks and seven parent-reared chicks quickly bonded back together," Kidd said.

"We found very slight behavioural differences - small enough to be explained by individual variation - and all chicks became embedded in the wider social network of the group.

"They all had favoured 'friends' to spend time with, which is normal flamingo behaviour."

Species including the Andean flamingo rare in captivity (only two flocks worldwide) and are classified as "vulnerable" in the wild.

Flamingos can be challenging to breed regularly in captivity, so the findings about successful fostering may help zoo conservation programmes.

"Foster rearing appears to be a safe method for conservation breeding of these species if done correctly," Dr Rose said.

"It is important to note that this fostering event went so smoothly because of the expert flamingo knowledge within the animal care teams at WWT."

The paper, published in the Journal of Zoo and Botanical Gardens, is entitled: "Influences of rearing environment on behaviour and welfare of captive Chilean flamingos: a case study on foster-reared and parent-reared birds."

A consortium of researchers from Russia, Belarus, Japan, Germany and France led by a Skoltech scientist have uncovered the way in which Mycobacterium tuberculosis survives in iron-deficient conditions by utilizing rubredoxin B, a protein from a rubredoxin family that play an important role in adaptation to changing environmental conditions. The new study is part of an effort to study the role of M. tuberculosis enzymes in developing resistance to the human immune system and medication. The paper was published in the journal Bioorganic Chemistry.

According to the World Health Organization, every year 10 million people fall ill with tuberculosis and about 1.5 million die from it, making it the world's top infectious killer. The bacterium that causes TB, Mycobacterium tuberculosis, is notorious for its ability to survive within macrophages, cells of the immune system that destroy harmful bacteria. Continuing spread of drug resistance of M. tuberculosis to widely used therapeutics over recent decades became a substantial clinical problem. In this regard, the identification of novel molecular drug targets and deciphering the molecular mechanisms of drug resistance are of pivotal importance.

Natallia Strushkevich, Assistant Professor at the Skoltech Center for Computational and Data-Intensive Science and Engineering (CDISE), and her colleagues studied the crystal structure and function of rubredoxin B (RubB), a metalloprotein that ensures the proper functioning of cytochrome P450 (CYP) proteins essential to bacterial survival and pathogenicity. The team hypothesizes that M. tuberculosis switched over to more iron-efficient RubB to survive iron starvation when granulomas are formed (these are largely unsuccessful attempts at defense against TB by the immune system).

"During the long-term co-evolution with mammals, M. tuberculosis developed a variety of strategies to subvert or evade the host innate immune response, from recognition of the bacterium and phagosomal defenses within infected macrophages, to adaptive immune responses by antigen presenting cells.

"Iron assimilation, storage and utilization is essential for M. tuberculosis pathogenesis and also involved in emergence of multi- and extensively-drug resistant strains. Heme is the preferable iron source for M. tuberculosis and serves as a cofactor for various metabolic enzymes. Based on our finding, we linked rubredoxin B to heme monoooxygenases important for metabolism of host immune oxysterols and anti tubercular drugs. Our findings indicate that M. tuberculosis has its own xenobiotics transformation system resembling human drug metabolizing system," explains Natallia Strushkevich.

According to Natallia: New targets for drug design efforts are in great demand and the cytochrome P450 enzymes have emerged as novel targets for the development of tuberculosis therapeutic agents. The classic approaches to block these enzymes are not straightforward. Finding the alternative redox partner, such as RubB, enables further understanding of their function in different host microenvironments. This knowledge could be exploited to identify new ways to block their function in M. tuberculosis.

Earlier research by the consortium showed that one of the CYPs enabled by RubB can act against SQ109, a promising drug candidate against multidrug-resistant tuberculosis. Another study focused on how Mycobacterium tuberculosis protects itself by intercepting human immune signaling molecules -- a hurdle that limits drug discovery.

A great need for better pain treatment

After an appendectomy, a quarter (24.8%) of all children wanted a stronger pain treatment in the first 24 hours after their operation. Among children who had a tonsillectomy, this was one-fifth (20.2%). Analysis of the data showed that this desire was primarily associated with sleep impairments and with movement pain. The lead author of the study, Prof. Ulrike M. Stamer, explained: "We are dealing with a large number of affected patients. Appendectomies and tonsillectomies are the most common operations performed on children overall. Just under a quarter of these cases strongly signal a desire for
improvement".

A comprehensive, multicentre study

This study is based on the international pain registry "PAIN OUT infant", which was established in 2015 to track the quality of postoperative pain management in children. The study included 472 children with appendectomies and 466 children with tonsillectomies. More pain-related impairments and side effects were reported in children who wanted a stronger pain treatment. They also received more opioids postoperatively (on average 81 versus 50 micrograms per kilogram of body weight).

Surprising result shows the way to optimisation

A surprising result emerged from the analysis of the survey data and a comparison with the medication used before and during the operations. It was found that children who had been given at least two different classes of non-opioid analgesics (NSAIDs, metamizole or paracetamol) as a precautionary measure were significantly less likely to ask for a stronger pain treatment when questioned 24 hours after surgery. Prof. Frank Stüber, head of the Department of Anesthesiology at Inselspital (University Hospital of Bern) is optimistic: "We have been able to identify a promising path with these study results. Precautionary administration of at least two different classes of non-opioid analgesics appears to be a way to reduce the use of higher doses of opioids after surgery".

TAMPA, Fla. (April 8, 2021) -- A dysfunctional immune system significantly contributes to the development of cancer. Several therapeutic strategies to activate the immune system to target cancer cells have been approved to treat different types of cancer, including melanoma. However, some patients do not show beneficial clinical responses to these novel and very promising immunotherapies. In a new article published in Proceedings of the National Academy of Sciences of the United States of America, Moffitt Cancer Center researchers demonstrate how an important defect in STING gene expression in melanoma cells contributes to their evasion from immune cell detection and destruction.

Several different mechanisms have been discovered that allow cancer cells to avoid immune cell detection and destruction, including defective T cell function, losses in expression of key proteins on tumor cells and defective cell signaling in both immune and tumor cells. An important signaling pathway that contributes to interactions between tumor cells and immune cells is the interferon signaling pathway. The interferon pathway increases expression of molecules that allow tumor cells to be recognized and killed by immune cells. One of the key molecules in the interferon signaling pathway is STING, which is activated by the protein cGAS.

Moffitt researchers previously demonstrated that STING activity is commonly suppressed and altered in a subset of melanomas, which prevents the ability of these tumor cells to be targeted by the immune system. The research team wanted to further the understanding of the importance of alterations in STING signaling in melanoma and determine how STING expression becomes suppressed. They focused on a process called epigenetic modification during which methylation groups are added to the DNA regulatory regions of genes, resulting in genes being turned off.

The researchers performed a series of laboratory experiments and discovered that the DNA regulatory region of the STING gene is highly modified by methylation groups resulting in loss of STING gene expression in certain melanoma cell lines. Importantly, they confirmed these findings in patient clinical samples of early and late-stage melanomas and showed similar methylation events and loss of expression of the upstream STING regulator cGAS.

Next, the researchers demonstrated that it is possible to reactivate expression of STING and/or cGAS with a demethylating drug or genetic approaches that overcome methylation. These interventions successfully turned on STING functional activity, resulting in increased interferon levels when triggered by STING agonist drugs that enabled the melanoma cells to now be recognized by immune cells and targeted for destruction.

These findings demonstrate for the first time that a strategy to overcome STING gene methylation can restore interferon signaling and immune cell activity in melanoma and improve a cell-based immunotherapy when combined with STING agonist drugs.

"These studies show the critical importance of an intact STING pathway in melanomas for optimal T cell immunotherapy success, and how to overcome a notable STING defect in melanoma cases of gene hypermethylation by a combination therapy," said James J. Mulé, Ph.D., senior author and associate center director for Translational Science at Moffitt. "Unless patients' melanomas are pre-screened for intact versus defective STING, it is not at all surprising that clinical trials of STING agonists have, to date, uniformly failed."

Genome mining combined metabolic shunting and OSMAC strategy of an endophytic fungus leads to the production of diverse natural products

Endophytic fungi are promising producers of bioactive small molecules. Bioinformatic analysis of the genome of an endophytic fungus Penicillium dangeardii revealed 43 biosynthetic gene clusters, exhibited its strong ability to produce numbers of secondary metabolites. However, this strain mainly produce rubratoxins alone with high yield in varied culture conditions, suggested most gene clusters are silent. Efforts for mining the cryptic gene clusters in P. dangeardii, including epigenetic regulation and one-strain-many-compounds (OSMAC) approach were failed probably due to the high yield of rubratoxins. A metabolic shunting strategy by deleting the key gene for rubratoxins biosynthesis combining with optimization of culture condition successfully activated multiple silent genes encoding for other polyketide synthases (PKSs), and led to the trace compounds detectable. As a result, the authors were able to identify a total of 23 new compounds including azaphilone monomers, dimers, trimers with unprecedented polycyclic bridged heterocycle and spiral structures, as well as siderophores. Some compounds showed significant cytotoxicities, anti-inflammatory or antioxidant activities. The attractive dual PKSs gene clusters for azaphilones biosynthesis were mined by bioinformatic analysis and overexpression of a pathway specific transcription factor. This research provides an efficient approach to mine the chemical diversity of endophytic fungi.

Discovery of novel diarylamides as orally active diuretics targeting urea transporters

Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In this study the authors discovered a novel UT inhibitor with a diarylamide scaffold by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate, N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide (1H), with excellent in vitro UT inhibitory activity at the submicromolar level. The half maximal inhibitory concentrations of 1H against UT-B in mouse, rat, and human erythrocyte were 1.60, 0.64, and 0.13 μmol/L, respectively.

Further investigation suggested that 8 μmol/L 1H more powerfully inhibited UT-A1 at a rate of 86.8% than UT-B at a rate of 73.9% in MDCK cell models. Most interestingly, the authors found for the first time that oral administration of 1H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in rats. Additionally, 1H did not exhibit apparent toxicity in vivo and in vitro, and possessed favorable pharmacokinetic characteristics. 1H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.

Using DNA structures as scaffolds, Tim Liedl, a scientist of Ludwig-Maximilians-Universitaet (LMU) in Munich, has shown that precisely positioned gold nanoparticles can serve as efficient energy transmitters. 

Since the inception of the field in 2006, laboratories around the world have been exploring the use of 'DNA origami' for the assembly of complex nanostructures. The method is based on DNA strands with defined sequences that interact via localized base pairing. "With the aid of short strands with appropriate sequences, we can connect specific regions of long DNA molecules together, rather like forming three-dimensional structures by folding a flat sheet of paper in certain ways," as Professor Tim Liedl of the Faculty of Physics at LMU explains.

Image and mirror image 

Liedl has now used DNA origami to construct chiral objects, i.e. structures that cannot be superimposed by any combination of rotation and translation. Instead they possess 'handedness', and are mirror images of one another. Such pairs often differ in their physical properties, for example, in the degree to which they absorb polarized light. This effect can be exploited in many ways. For example, it is the basis for CD spectroscopy (the 'CD' here stands for 'circular dichroism'), a technique that is used to elucidate the overall spatial configuration of chemical compounds, and even whole proteins.

With a view to assembling chiral metal structures, Liedl and his group synthesized complex DNA-origami structures that provide precisely positioned binding sites for the attachment of spherical and rod-shaped gold nanoparticles. The scaffold therefore serves as a template or mold for the placement of nanoparticles at predetermined positions and in a defined spatial orientation. "One can assemble a chiral object based solely on the arrangement of the gold nanoparticles," says Liedl 

Gold is not only chemically robust, as a noble metal it exhibits what are known as surface plasmon resonances. Plasmons are coherent electron oscillations that are generated when light interacts with the surface of a metal structure. "One can picture these oscillations as being like the waves that are excited when a bottle of water is shaken either parallel or at right angles to its long axis," says Liedl. 

Gold nanoparticles as energy transmitters

Oscillations excited in spatially contiguous gold particles can couple to one another, and the plasmons in Liedl's experiments behave as image and mirror image, thanks to their chiral disposition on the origami scaffold. "This is confirmed by our CD spectroscopic measurements," says Liedl. In the experiments, the chiral structures are irradiated with circularly polarized light and the level of absorption is measured as a percentage of the input. This enables right- and left-handed arrangements to be distinguished from one another.

In principle, two gold nanorods should be sufficient for the construction of chiral object, as they can be arranged either in the form of an L or an inverted L. However, the rods used in the experiments were relatively far apart (on the nanoscale) and the plasmons excited in one had little effect on those generated in the other, i.e. the two hardly coupled to each other at all. But Liedl and his colleagues had a trick up their sleeves. By appropriate redesign of the origami structure, they were able to position a gold nanosphere between the pair of L-formed rods, which effectively amplified the coupling. CD spectroscopy revealed the presence of energy transitions, thus confirming the hypothesis which the team had derived from simulations.

Liedl envisages two potential settings in which these nanostructures could find practical application. They could be used to detect viruses, since the binding of viral nucleic acids to a gold particle will amplify the CD signal. In addition, chiral plasmonic transmitters could serve as model switching devices in optical computers, in which optical elements replace the transistors that are the workhorses of electronic computers. 

Orchids of the Boreal zone are rare species. Most of the 28,000 species of the Orchid family actually live in the tropics. In the Boreal zone, ground orchids can hardly tolerate competition from other plants -- mainly forbs or grasses. So they are often pushed into ecotones -- border areas between meadows and forests, or between forests and swamps.

Furthermore, there has been a decline in wild orchids all over North America and Eurasia, caused in part by human-induced destruction of their habitats, the transformation of ecosystems, and the harvesting of flowers from the wild.

In the Novosibirsk region, 30 orchid species have been found, and about 40 in the entire Siberia.

It is no coincidence that many orchids are included in regional and national Red Book lists, with dedicated protected areas created to preserve them. When specialists find high concentrations of orchid species in a small area, it is always a significant discovery, in terms of both science and ecology. A recent publication in the open-access, peer-reviewed scientific journal Acta Biologica Sibirica describes one such area.

About 15 years ago, local biology teacher Yuri Panov found a place with mass growth of 13 orchid species in the Novosibirsk region. Together with his students, he studied the territory and took care of it, hanging birdhouses. The place was informally called School Orchid Zapovednik.

In 2014, a wildfire from nearby farm fields broke out in the area. Fortunately, the orchid populations did not suffer much - in fact, this disturbance partially contributed to their growth in some areas, reducing competition from grasses and shrubs. However, the danger of frequent fires prompted Panov to invite specialists for a thorough botanical survey of the territory.

Researchers Alexander Dubynin, Inessa Selyutina and Alexandra Egorova of the Central Siberian Botanical Garden in Novosibirsk, and Mikhail Blinnikov of Kazan Federal University have been working in the area since 2017, registering the occurrences of orchids and photographing plants for the iNaturalist platform. There and in adjacent territories, they discovered a total of 14 orchid species, some of which were new to this territory and had never been registered before.

The area in Novosibirsk region is truly unique. Here, researchers found one of the largest populations of large-flowered lady's-slipper (Cypripedium macranthos) in Northern Eurasia, with up to 5,000 individual plants. The Cypripedium calceolus Lady's-slipper orchid and the rare and beautiful bloated lady's slipper (Cypripedium ventricosum) were also plentiful. Some of the discovered orchids require further study, such as the hybrids between Dactylorhiza and Gymnadenia and some unusual forms of Platanthera.

After an expert description of the territory, a new Important Plant Area was nominated for South Siberia. "Based on the analysis of plant species composition of protected areas in Novosibirsk Region," Alexander Dubynin resumes, "we conclude that in situ preservation of orchids in the region is overall insufficient. It is therefore necessary to organize a new protected area 'Orchid Zapovednik' in the category of 'botanical Zakaznik' on 335 hectares with an explicit floral diversity conservation mandate and long-term orchid population monitoring."

Over the past three years, the territory has increasingly attracted the attention of researchers and educators, becoming a kind of a 'field laboratory' for the study of orchid communities in South Siberia.

Scientists have made a pivotal breakthrough in understanding the way in which cells communicate with each other.

A team of international researchers, including experts from the University of Exeter's Living Systems Institute, has identified how signalling pathways of Wnt proteins - which orchestrate and control many cell developmental processes - operate on both molecular and cellular levels.

Various mechanisms exist for cells to communicate with each other, and many are essential for development. This information exchange between cells is often based on signalling proteins that activate specific intracellular signalling cascades to control cell behaviour at a distance.

Wnt proteins are produced by a relatively small group of cells and orchestrate cell proliferation and differentiation, but also cell movement and polarity of the neighbouring cells.

However, one of the most crucial functions of the Wnt signalling is patterning of the body axis - which essentially helps determine where the head and tail should form in in a developing tissue.

Previous research led by Professor Steffen Scholpp, from the Living Systems Institute, highlighted that thin finger-like protrusions, known as cytonemes, carry Wnts from the source cells to recipient cells.

However, the mechanism controlling Wnt cytonemes at the molecular level is currently unknown.

In the new study, his team explored the role of a key component of the PCP signalling pathway Vangl2 in zebrafish embryos.

In this project, Dr Lucy Brunt, identified that Wnt proteins activate the PCP pathway in a source cell in order to regulate cytoneme initiation and signal dissemination.

By activating this pathway via Vangl2, she induced the formation of long and branched cytonemes which reinforced distant Wnt signalling in the neighbouring cells.

Based on these data, fellow researcher Dr Kyle Wedgwood and his team developed a mathematical model to simulate this effect in a developing zebrafish egg, and predicted that the patterning of the body axis is massively altered.

"And the prediction was correct" explained Dr Brunt. " We found that the formation of longer cytonemes in zebrafish larvae led to a strongly reduced head, and strikingly the forebrain tissue was missing completely."

Together with cell biologists from the National University of Singapore, the scientists showed that the mechanism they described in zebrafish embryogenesis, operates also in different tissues, including human cancer cells.

Professor Scholpp said "The exciting results of this multidisciplinary, multiscale project provides a step change in understanding how the Wnt signalling pathway operates at the molecular and cellular level in a living vertebrate animal.

"The data from this project will help us to understand the mechanisms involved in controlling normal Wnt signalling, in the future," he added. "We believe that the outcome will have fundamental implications for how we could manipulate Wnt signalling during disease states."

Dengue risk is exacerbated in highly populated areas of Brazil after extreme drought because of improvised water containers housing mosquitoes, suggests a new study in Lancet Planetary Health.

The research was led by the London School of Hygiene & Tropical Medicine's (LSHTM) Centre on Climate Change & Planetary Health and Centre for the Mathematical Modelling of Infectious Diseases. Using advanced statistical modelling techniques, the team predicted the timing and intensity of dengue risk in Brazil from extreme weather patterns.

The risk of dengue was high in urban areas three to five months after extreme drought. Extremely wet conditions increased dengue risk in the same month and up to three months later. In rural areas, dengue risk was more readily associated with very wet conditions.

Dengue fever is caused by a virus carried by mosquitoes and is considered one of the top ten threats to global health. Brazil has the greatest number of dengue cases in the world, reporting more than two million cases of dengue in 2019 alone.

Increasing levels of severe droughts and flooding episodes due to climate change has led to interruptions in water supply networks in Brazil. The improvised water storage containers used to combat this have become breeding grounds for mosquitoes.

Dr Rachel Lowe from LSHTM who led the study, said: "The dengue situation in Brazil is extremely concerning. Our work highlights that risk is not only related to extreme weather, but also linked to water management systems and human behaviour in densely populated urban areas."

In Brazil, large dengue outbreaks are typically observed after wet and warm periods and most interventions are targeted at these times. No studies have previously determined exact timeframes for dengue outbreaks following extreme weather events like droughts and floods across a large and diverse geographical area, although this work confirms initial findings from Barbados.

In this new study, the team combined dengue case data in 558 regions of Brazil between January 2001 and 2019, with information on droughts and wet conditions to assess the dengue risk differences in urban and rural areas.

The results suggest dengue interventions should be timed appropriately in poorly serviced urban areas and not only implemented during the wet and warm season.

In the short term, these include eliminating breeding sites around the home to prevent additional mosquito larval habitats during drought periods. During wet periods, outdoor water storage containers should be well covered and maintained, and discarded waste should be cleared to avoid collecting water.

Dr Lowe said: "It's imperative that governments invest in local infrastructure to ensure permanent water supply and promote better environmental hygiene in areas prone to epidemics of mosquito-borne diseases."

The study carries some limitations as the dengue data was obtained from the passive surveillance system, where only a fraction of cases are laboratory confirmed and mild or asymptomatic cases are not accounted for.