Tech

Australians love their beaches, and now a new study also confirms the broad appeal of other coastal assets such as tidal wetlands, nature trails and protected areas including bird and dolphin sanctuaries.

In one of the first studies of its kind in Australia, ahead of World Wetlands Day (2 February), Flinders University environment and marine ecology experts have conducted an Adelaide-based survey of how residents connect with and rate the attributes of Adelaide's northern metropolitan coastal wetlands.

The findings, just published in the journal Environmental Science and Policy, report strong appreciation of the natural features of these coastal places, with study participants rating them highly - and identifying their importance for personal wellbeing which underpins a need for closer controls on further development or degradation of these important community spaces, researchers say.

"People who visited the study region for recreation and work identified a personal bond with the places like Adelaide's Dolphin Sanctuary, the International Bird Sanctuary and St Kilda Mangrove Trail and other coastal national parks and coastal features situated so close to the city - added reasons to take good care of these precious resources," says lead author, Flinders University geographer Associate Professor Beverley Clarke.

The study used a 'cultural ecosystem services' framework to assess residents' perceptions about the benefits they gained from these wetlands.

"Translating the benefits people receive from coastal ecosystems in a way that is usable to policy-makers and environmental managers is important but challenging," says Associate Professor Clarke.

"Here we have been able to document health and wellbeing benefits expressed by the people who experience these places. As well as simply appreciating the natural landscape, it is through their activities that citizens developed an attachment to the coastline.

"People value these places as they become familiar with them," say Associate Professor Clarke, a life member of the Australian Coastal Society, who researches coastal planning and management with a current focus on strategies to support adaptation and resilience of coastal communities to the impacts of climate change.

Co-author marine biologist, Professor Sabine Dittmann, an expert in coastal ecosystem ecology and blue carbon at Flinders University's College of Science and Engineering, says this social values survey highlights the co-benefits of coastal restoration.

"Naturalness of coastal wetlands matters most to people and will be an important outcome from restoring tidal wetlands, in addition to carbon sequestration gains," she says.

Professor Dittmann is involved in carbon sequestration and saltmarsh restoration projects at Dry Creek north of Adelaide.

Irrespective of their socio-ecological and climatic importance, coastal wetlands around the world are among the most threatened of all environments, facing human-induced pressures of landscape modification for agriculture and urbanisation, and climate-induced sea level rises.

The researchers note that building awareness of the social benefits of restoring these sometimes under-appreciated wetlands may help generate support for protecting - rather than developing - these threatened landscapes.

Nagoya University researchers and colleagues have revealed that colorectal cancer tissues contain at least two types of fibroblasts (a type of cells found in connective tissue), namely, cancer-promoting fibroblasts and cancer-restraining fibroblasts, and that the balance between them is largely involved in the progression of colorectal cancer. Their findings, recently published in the journal Gastroenterology, suggest that artificially altering the balance between the two types of cells could curb the spread of colorectal cancer tumors, which may become an effective strategy for preventing cancer progression.

Cancer tissues comprise both cancer cells and non-malignant cells such as fibroblasts. Previous studies have suggested that the proliferation of fibroblasts is largely involved in the progression of colorectal cancer, the most common cancer in Japan. Fibroblasts within cancer tissues, called cancer-associated fibroblasts (CAFs), are considered to be divided into at least two populations: those that promote cancer progression and those that restrain it. Impeding the function of cancer-promoting CAFs could be a promising method to prevent cancer progression, but a lack of understanding of the mechanism underlying heterogeneity of CAFs has hampered its development.

In normal colon tissues, proteins called bone morphogenetic proteins (BMPs), which are secreted by stromal cells, are known to play a critical role in regulating intestinal homeostasis, whereas in cancerous colon tissues, they are considered to be associated with cancer progression. In this context, the research team led by Professors Atsushi Enomoto and Masahide Takahashi of the Graduate School of Medicine at Nagoya University in Japan conducted a study to determine how stroma cells lead BMPs to be involved in the progression of colorectal cancer.

The team first analyzed comprehensive gene expression profiling data to identify BMP-related genes that are specifically expressed in colorectal CAFs. Two types of proteins, meflin and gremlin 1, were identified to be encoded by such genes. Next, to investigate the relevance of these proteins in colorectal cancer progression, Prof. Enomoto and his colleagues, who had previously shown that meflin plays a role in restraining the progression of pancreatic cancer, conducted a study in collaboration with researchers from the University of Adelaide and the South Australian Health and Medical Research Institute, who have conducted studies focusing on the role of gremlin 1 as a BMP inhibitor in the intestine.

The joint research group examined the prognostic significance of the expression of meflin and gremlin 1 in colorectal cancer patients and found that, interestingly, those with a high expression of meflin have a favorable prognosis, whereas those with a high expression of gremlin 1 have an unfavorable prognosis. In addition, experiments using a mouse model revealed that the proliferation of colorectal cancer cells can be suppressed through administration of a gremlin 1-neutralizing antibody or overexpression of meflin.

Regarding the role of BMP signaling mediated by stromal gremlin 1 and meflin in colorectal cancer, Prof. Enomoto explains, "We hypothesize that CAFs mediated by gremlin 1 promote cancer progression by decreasing BMP signaling, whereas CAFs mediated by meflin restrain the growth of the cancer by reinforcing BMP signaling." Therefore, intensifying stromal BMP signaling, either by using a gremlin 1-neutralizing antibody or by overexpressing meflin, could be an attractive therapeutic strategy to treat colorectal cancer.

An international team of researchers produced islands of amorphous, non-crystalline material inside a class of new metal alloys known as high-entropy alloys.

This discovery opens the door to applications in everything from landing gears, to pipelines, to automobiles. The new materials could make these lighter, safer, and more energy efficient.

The team, which includes researchers from the University of California San Diego and Berkeley, as well as Carnegie Mellon University and University of Oxford, details their findings in the Jan. 29 issue of Science Advances.

"These present a bright potential for increased strength and toughness since metallic glasses (amorphous metals) have a strength that is vastly superior to that of crystalline metals and alloys," said Marc Meyers, a professor in the Department of Mechanical and Aerospace Engineering at UC San Diego, and the paper' s corresponding author.

Using transmission electron microscopy, which can identify the arrangement of atoms, the researchers concluded that this amorphization is triggered by extreme deformation at high velocities. It is a new deformation mechanism that can increase the strength and toughness of these high entropy alloys even further.

The research is based on seminal work by Brian Cantor at the University of Oxford, and Jien-Wei Yeh at National Tsing Hua University in Taiwan. In 2004, both researchers led teams that reported the discovery of high-entropy alloys. This triggered a global search for new materials in the same class, driven by numerous potential applications in the transportation, energy, and defense industries.

"Significant new developments and discoveries in metal alloys are quite rare," Meyers said.

Researchers at the University of Arizona are developing a COVID-19 testing method that uses a smartphone microscope to analyze saliva samples and deliver results in about 10 minutes.

The UArizona research team, led by biomedical engineering professor Jeong-Yeol Yoon, aims to combine the speed of existing nasal swab antigen tests with the high accuracy of nasal swab PCR, or polymerase chain reaction, tests. The researchers are adapting an inexpensive method that they originally created to detect norovirus - the microbe famous for spreading on cruise ships - using a smartphone microscope.

They plan to use the method in conjunction with a saline swish-gargle test developed by Michael Worobey, head of the UArizona Department of Ecology and Evolutionary Biology and associate director of the University of Arizona BIO5 Institute.

The team's latest research using water samples - done in collaboration with Kelly A. Reynolds, chair of the Department of Community, Environment and Policy in the UArizona Mel and Enid Zuckerman College of Public Health - is published today in Nature Protocols.

"We've outlined it so that other scientists can basically repeat what we did and create a norovirus-detecting device," said Lane Breshears, a biomedical engineering doctoral student in Yoon's lab. "Our goal is that if you want to adapt it for something else, like we've adapted it for COVID-19, that you have all the ingredients you need to basically make your own device."

Yoon - a BIO5 Institute member who is also a professor of biosystems engineering, animal and comparative biomedical sciences, and chemistry and biochemistry - is working with a large group of undergraduate and graduate students to develop the smartphone-based COVID-19 detection method.

"I have a couple of friends who had COVID-19 that were super frustrated, because their PCR results were taking six or seven days or they were getting false negatives from rapid antigen tests. But when they got the final PCR tests, they found out they had been sick, like they'd suspected," said Katie Sosnowski, a biomedical engineering doctoral student who works in Yoon's lab. "It's really cool to be working on a detection platform that can get fast results that are also accurate."

Cheaper, Simpler Detection

Traditional methods for detection of norovirus or other pathogens are often expensive, involve a large suite of laboratory equipment or require scientific expertise. The smartphone-based norovirus test developed at UArizona consists of a smartphone, a simple microscope and a piece of microfluidic paper - a wax-coated paper that guides the liquid sample to flow through specific channels. It is smaller and cheaper than other tests, with the components costing about $45.

The basis of the technology, described in a 2019 paper published in the journal ACS Omega, is relatively simple. Users introduce antibodies with fluorescent beads to a potentially contaminated water sample. If enough particles of the pathogen are present in the sample, several antibodies attach to each pathogen particle. Under a microscope, the pathogen particles show up as little clumps of fluorescent beads, which the user can then count. The process - adding beads to the sample, soaking a piece of paper in the sample, then taking a smartphone photograph of it under a microscope and counting the beads - takes about 10 to 15 minutes. It's so simple that Yoon says a nonscientist could learn how to do it by watching a brief video.

The version of the technology described in the Nature Protocols paper makes further improvements, such as creating a 3D-printed housing for the microscope attachment and microfluidic paper chip. The paper also introduces a method called adaptive thresholding. Previously, researchers set a fixed value for what quantity of pathogen constituted a danger, which limited precision levels. The new version uses artificial intelligence to set the danger threshold and account for environmental differences, such as the type of smartphone and the quality of the paper.

On-Campus Impact

The researchers plan to partner with testing facilities at the University of Arizona to fine-tune their method as they adapt it for COVID-19 detection. Pending approval of the university's institutional review board, students who are already being tested on campus through other methods will have the option to provide written consent for their sample to be run through the smartphone-based testing device as well. Ultimately, the researchers envision distributing the device to campus hubs so that the average person - such as a resident assistant in a dorm - could test saliva samples from groups of people.

"Adapting a method designed to detect the norovirus - another highly contagious pathogen - is an outstanding example of our researchers pivoting in the face of the pandemic," said University of Arizona President Robert C. Robbins. "This promising technology could allow us to provide fast, accurate, affordable tests to the campus community frequently and easily. We hope to make it a regular part of our 'Test, Trace, Treat' strategy, and that it will have a broader impact in mitigating the spread of the disease."

Yoon and his team are also working on another idea, based on a 2018 paper they published in Chemistry--A European Journal, which is even simpler but leaves slightly more room for error. It involves the same technology, but instead of a smartphone microscope and specially designed enclosure, users would only need to download a smartphone app and use a microfluidic chip stamped with a QR code.

"Unlike the fluorescent microscope technique, where you get the chip into just the right position, you just take a snapshot of the chip," said biomedical engineering master's student Pat Akarapipad. "No matter the angle or distance the photo is taken from, the smartphone app can use AI and the QR code to account for variances and run calculations accordingly."

The method requires no training, so, if perfected, it could potentially allow students to pick up microfluidic chips from a campus location and test their own samples.
The team is also working with other members of the university's COVID-19 testing group, including Deepta Bhattacharya, an associate professor in the Department of Immunobiology.

[Abstract]

The National Institute of Information and Communications Technology (NICT), Tohoku University, Toin University of Yokohama, and Japan Science and Technology Agency (JST) have succeeded in developing a scanless high-speed holographic fluorescence microscopy system with submicron resolution for a 3D space. The system is based on digital holography. The developed microscopy system has an algorithm to acquire 3D information of fluorescent objects toward scanless 3D measurement in less than 1 millisecond. Scanless 3D sensing with submicron resolution and color-multiplexed holographic fluorescence imaging have been demonstrated using the algorithm. The microscopy system will be further developed to achieve holographic 3D motion-picture sensing of specimens with incoherent light.

This achievement was published in Optics Letters as an open-access paper on January 29, 2021.

[Achievements]

The scanless high-speed holographic fluorescence microscopy system shown in Figure 1 was constructed. The system is based on digital holography and is applicable to the sensing of incoherent light such as fluorescence light and natural light. The developed algorithm enables the adoption of a phase modulator to generate two phase values, which is expected to increase the measurement speed. Submicron resolution for a 3D space was successfully demonstrated using fluorescent objects with a diameter of 0.2 micron. The experimental results shown in Figure 2 indicate that the developed microscopy system achieves 3D sensing of nanoparticles and has submicron resolution quantitatively for a 3D space. Scanless 3D measurement in less than 1 millisecond is achievable by using the algorithm with either a ferroelectric liquid crystal on silicon (FLCOS) or an electro-optic (EO) device. Color-multiplexed holographic fluorescence imaging with the algorithm and only four exposures has also been demonstrated by combining the proposed algorithm and computational coherent superposition (CCS). The number of exposures is reduced by the algorithm, and the number of photons per hologram is increased even for ultimately weak light.

[Future prospects]

High-speed holographic motion-picture imaging for 3D dynamics and multiple moving objects in a 3D space.

Improvements of the system such as recording of a quantitative phase, sensing of ultimately weak light, and construction of a compact optical setup.

Thrombosis, the clogging of blood vessels, is a major cause of heart attacks and embolism. Scientists have now engineered the first inhibitors of thrombin, a protease promoting thrombosis, that is three-fold efficient. In a study published in the journal Angewandte Chemie, the authors demonstrate that attacking three sites of the thrombin molecule is more efficient than attacking only two sites, which is the mode of action of many natural agents.

Soon after an injury, thrombin appears at the site of the wound, promoting platelet coagulation and fibrin development to clog the wound and grow new tissue. Unfortunately, inside blood vessels uncontrolled thrombin activity may lead to clogged pathways causing fatal outcomes for patients. Thrombosis has come into focus recently when it appeared that it was one of the major complications of severe COVID-19.

Many biting and blood-sucking insects carry natural anti-thrombosis factors to keep the blood in a wound liquid. Some of these natural inhibitors have been turned into medicine. The most applied thrombin inhibitor is hirudin, a peptide isolated from leeches.

In their quest to optimize thrombin inhibition, Richard J. Payne from the University of Sydney, Australia, in collaboration with an international team of scientists, scrutinized the way the inhibitors act. Most thrombin inhibitors from insects block two sites on thrombin. Usually, they attack the active site (the substrate-cleaving site) plus one of two other regions on the surface of the enzyme, which are important for regulating coagulation.

To cover all three sites with one drug, the researchers chose three natural inhibitors, which were then patched together. They connected the tsetse thrombin inhibitor, or TTI, from the tsetse fly with either an inhibitor peptide called variegin from a tropical tick or the inhibitor anophelin from the malaria mosquito Anopheles. The resulting hybrid peptides were designed to span all three binding sites of thrombin.

This design proved to be efficient. According to the authors, the "constructs from both hybrid series exhibited exquisitely potent thrombin inhibitory activities." The scientists reported up to 385-fold inhibition for the hybrid involving the peptides from tsetse fly and Anopheles mosquito. For the other hybrids, the improvements were still 2- to 10-fold. Notably, in human plasma all hybrids inhibited thrombin generation and platelet aggregation.

To test the constructs in a live body, the researchers applied one of the hybrids to a mouse model. Here, it made a thrombus shrink at least with the same efficiency as hirudin, and it reduced fibrin accumulation. The authors hope that this work will not only lead to efficient anticoagulation drugs, but will also help in the design of other peptide-based agents.

Researchers have completed the first ever multi-level hydrological tracking of the Yangtze River from the ground, air and space in order to investigate the properties of cloud formation during the mei-yu--an intense rainy season that forms part of East Asia's summer monsoon. The effort should permit greater understanding of the mei-yu precipitation process and thus enable much more accurate forecasts of this key meteorological phenomenon in the region.

The mei-yu, also known as the "Plum Rain", is a period of severe, concentrated rainfall that lasts for up to two months during the late spring and early summer, covering mainland China, Taiwan, Japan and Korea.

This intense weather phenomenon arises from interactions between systems of convection (transfer of heat within a fluid) at multiple, mid-range or "mesoscale" levels, ranging from 2-20 km up to 20-200 km. These are considered mesoscale because they develop at a larger level than "microscale", or under 1 km-sized phenomena, such as small, fleeting, cloud "puffs", but still smaller than "synoptic scale" phenomena over 1000 km such as cyclones.

Conventional observations cannot deliver the detailed spatial and temporal variations that exist within such mid-ranking multi-scale convective systems. Nor can they describe their cloud structures or "microphysical" processes and properties. As a result, researchers with the Hubei Key Laboratory for Heavy Rain Monitoring and Warning Research, at the China Meteorological Administration's Institute of Heavy Rain, organized an ambitious monitoring effort that itself works at multiple levels along the middle and lower reaches of the Yangtze River.

The Integrative Monsoon Frontal Rainfall Experiment (IMFRE-II) took place during ten heavy rainfall events of the 2020 mei-yu and employed ground-based, airborne and satellite observations.

"Last year's mei-yu was a particularly extreme one that broke records," said meteorologist Chunguang Cui, lead author of the study, published on Jan 5 in the journal Advances in Atmospheric Sciences . It lasted 44 days, some 19 days longer than average--the eighth longest mei-yu since 1951, at a greater than normal intensity, and over a larger area. "This was a gift in terms of the data we were able to gather."

The campaign involved the use of seven aircraft flights measuring various attributes of ice particles, cloud droplets and raindrops at various altitudes, as well as seven grown-based observation systems and global precipitation measurement (GPM) satellites.

IMFRE-II followed on from IMFRE-I, which was conducted in 2018 over the middle reaches of the Yangtze. In 2022, the researchers hope to carry out a third such effort.

In combination, the three field campaigns will allow the researchers to investigate the microphysical properties of clouds and precipitation in a mei-yu, and significantly improve the computer models describing how the mei-yu system forms and later disperses. This will in turn give a big boost to the accuracy of mei-yu forecasts, of enormous benefit to the agricultural sector and flood protection planning.

New particle formation (NPF) is a major source of aerosol particles in the global atmosphere. In polluted megacities, such as Beijing, the role of new particle formation events and their contribution to haze formation through subsequent growth is still unclear.

To improve the understanding of the sources, meteorological conditions, and chemistry behind air pollution, the research teams led by Prof. Yele Sun with the Institute of Atmospheric Physics at the Chinese Academy of Sciences and Prof. Markku Kulmala with the University of Helsinki performed simultaneous measurements of aerosol composition and particle number size distributions at ground level and at 260 m in central Beijing, China, during a total of 4 months in 2015-2017. Their study was recently published in npj Climate and Atmospheric Science.

"The haze formation is initiated by the growth of freshly formed particles at both ground level and city aloft. However, the haze was more severe at ground level because of higher particle growth rates due to the impacts of local primary particles and gaseous precursors." said Prof. Sun.

According to Prof. Sun, the particle growth creates a feedback loop, in which a further development of haze increases the atmospheric stability. It in turn strengthens the persisting apparent decoupling between the two heights and increases the severity of haze at ground level.

The team further complemented the field observations with NAQPMS+APM model analyses, and found that the haze associated with NPF and growth was formed on a regional scale in Beijing-Tianjin-Hebei area. Prof. Sun said, "The growth of NPF-originated particles accounts for up to ?60% of the accumulation mode particles, and drives the haze formation in the Beijing-Tianjin-Hebei area."

The team also performed simulations on how emission reductions would affect haze development. "Concentration of both primary and secondary particles in the accumulation mode would decrease drastically, and the haze formation would be reduced if the emission cuts are higher than 30%." Concluded Prof. Sun. "Our results show that a reduction in anthropogenic gaseous precursors can suppress particle growth, and therefore is a critical step for haze alleviation."

Large parts of today's Sahara Desert were green thousands of years ago. Prehistoric engravings of giraffes and crocodiles testify to this, as does a stone-age cave painting in the desert that even shows swimming humans. However, these illustrations only provide a rough picture of the living conditions. Recently, more detailed insights have been gained from sediment cores extracted from the Mediterranean Sea off the coast of Libya. An international research team examined these cores and discovered that the layers of the seafloor tell the story of major environmental changes in North Africa over the past 160,000 years. Cécile Blanchet of the German Research Centre for Geosciences GFZ and her colleagues from Germany, South Korea, the Netherlands and the USA report on this in the journal Nature Geoscience.

Together with the GEOMAR Helmholtz Centre for Ocean Research Kiel, a team of scientists organized a research cruise on the Dutch vessel Pelagia to the Gulf of Sirte in December 2011. "We suspected that when the Sahara Desert was green, the rivers that are presently dry would have been active and would have brought particles into the Gulf of Sirte", says lead author Cécile Blanchet. Such sediments would help to better understand the timing and circumstances for the reactivation of these rivers.

Using a method called "piston coring", the scientists were able to recover 10-meters long columns of marine mud. "One can imagine a giant hollow cylinder being pushed into the seafloor", says co-author Anne Osborne from GEOMAR, who was onboard the research ship. "The marine mud layers contain rock fragments and plant remains transported from the nearby African continent. They are also full of shells of microorganisms that grew in seawater. Together, these sediment particles can tell us the story of past climatic changes", explains Blanchet.

"By combining the sediment analyses with results from our computer simulation, we can now precisely understand the climatic processes at work to explain the drastic changes in North African environments over the past 160,000 years", adds co-author Tobias Friedrich from the University of Hawai'i.

From previous work, it was already known that several rivers episodically flowed across the region, which today is one of the driest areas on Earth. The team's unprecedented reconstruction continuously covers the last 160,000 years. It offers a comprehensive picture of when and why there was sufficient rainfall in the Central Sahara to reactivate these rivers. "We found that it is the slight changes in the Earth's orbit and the waxing and waning of polar ice sheets that paced the alternation of humid phases with high precipitation and long periods of almost complete aridity", explains Blanchet.

The fertile periods generally lasted five thousand years and humidity spread over North Africa up to the Mediterranean coast. For the people of that time, this resulted in drastic changes in living conditions, which probably led to large migratory movements in North Africa. "With our work we have added some essential jigsaw pieces to the picture of past Saharan landscape changes that help to better understand human evolution and migration history", says Blanchet. "The combination of sediment data with computer-simulation results was crucial to understand what controlled the past succession of humid and arid phases in North Africa. This is particularly important because it is expected that this region will experience intense droughts as a consequence of human-induced climate change."

Who hasn't at some point been chewing on an almond and tasted an unpleasant and unexpected aftertaste that has nothing to do with the taste we are used to from one of the most consumed nuts in the world? The culprit has a name: amygdalin, a diglucoside that, when in contact with enzymes present in saliva, breaks down into glucose, benzaldehyde (the cause of the bitter taste) and hydrogen cyanide.

To reduce this unpleasant 'surprise', the Farming Systems Engineering (AGR-128) and Food Technology (AGR-193) research groups at the University of Cordoba's School of Agricultural and Forestry Engineering, with collaboration from the Andalusian Institute of Agricultural Research and Training's Alameda del Obispo Center, developed method that can predict levels of the abovementioned amygdalin present in the nuts analyzed both with and without shells, as well as correctly classify sweet almonds and bitter ones on an industrial scale, something that has only been done with shelled nuts, individual kernels or ground nuts to date.

The new system uses portable equipment based on NIRS technology -Near Infrared Spectroscopy- which can analyze large amounts of a product in situ in real time, without having to go into a lab. This technological application is "of great interest to the farming sector", explains Professor Dolores Pérez Marín, since almond bitterness in the wild can be helpful to prevent predators from ingesting the seeds of certain varieties, but on an industrial scale it offers no advantages and many disadvantages: an unpleasant taste, product devaluation and potential problems with food safety if consumption of bitter nuts occurs on a large scale.

Technically, the NIRS sensors use a beam of light that, when interacting with organic matter, returns a unique signal (spectrum) for each product sample, as in an unmistakable digital print that provides information and allows us to define the sample. In this case, as explained by doctoral student and first author of the research paper, Miguel Vega Castellote, the portable sensors, "whose signal along with the reference values allow for the development of prediction models", are able to analyze different parameters by "scanning" the product quickly and noninvasively, as in without modifying it.

Food fraud

Using NIRS technology, in which the research team has vast experience with an array of food products, is especially useful in the early detection of possible fraud and in food authentication. Therefore, the team has initiated another research project aimed at detecting batches of sweet almonds adulterated with bitter ones and in which almost 90% of the fraudulent items were identified. The system tested in this research, explains Professor María Teresa Sánchez Pineda de las Infantas, another author of the paper "could be implemented at any point in the value chain, including upon reception, during processing and shipping, and could be used as a fast and affordable anti-fraud early warning method".

Using the developing eye of the fruit fly as a test platform, researchers found that RPS-12 protein overproduction appears to trigger triple-negative breast cancer and possibly some other malignancies. The protein indirectly switches on an important inracellular signaling pathway active while the embryo develops and shut down in healthy cells of adults. Far Eastern Federal University (FEFU), the University of Geneva, and the Institute of Protein Research (Russia) scientists addressed the problem in Scientific Reports.

Researchers have taken another step towards targeted treatment of tumors. The idea of such a therapy is to identify the necessary target proteins playing instructive functions in tumor initiation or progression in order to suppress tumor development while causing minimal harm to healthy cells.

Using fruit flies and a cDNA library of patient-derived triple-negative breast cancer, scientists launched a massive screening for potential novel human oncogenes, i.e. genes that after a mutation activate elements of cancerous transformation. To find the potential targets, scientists inserted genes found in the human tumor into the Drosophila genome, drove their misexpression in the eye of the insect, and observed the potential defects in the development of this sensitive organ.

After they transplanted the human protein RPS-12, the Drosophila eye shrank and obtained a mirror-like appearance.

"This phenomenon reminds the classic glazed phenotype that Thomas Morgan, the father of Drosophila genetics, discovered back in the 1920s. Only in the 90s of the 20th century, it was understood that the mutation affects the Wingless gene. This Drosophila gene corresponds to the WNT genes that trigger the signaling pathway of the same name in humans. The activity of the WNT signaling pathway is vital for the development of the human body at the embryonic stage, though switched off at later stages. Mutations or epigenetic changes can reboot the signaling pathway in adults. After that, the initially healthy cells start a massive proliferation. This is one of the reasons for the development of triple-negative breast cancer and some other forms of cancer, such as in the colon, liver, ovaries, etc.", explains Vladimir Katanaev, the project ideologist, head of the laboratory of pharmacology of natural compounds at the FEFU School of Biomedicine.

Scientists revealed that the phenotype of the glazed eye arises because the expression of human RPS12 in the eye of Drosophila overactivates the WNT / Wingless-signaling pathway. The overabundance of RPS12 protein stimulates the production of active forms of Wingless capable of diffusing over long distances in the tissue and reaching distant cells. Reciprocally, the reduced amount of RPS12 decreases the production of such Wingless forms.

"The proteins of the Wingless-WNT family are very "sticky". Their natural distribution in the body tissues is limited, and the number of active forms migrating over long distances is under strict regulation. WNT is an example of morphogens, i.e. substances that are produced in specific places during embryogenesis and spread through the tissue generating a concentration gradient. If we consider a human hand as an example, the palm, elbow, and shoulder are formed due to the reaction of cells to different concentrations of the WNT morphogen", says Vladimir Katanaev.

Special mechanisms are responsible for the production of WNT-forms capable of spreading through tissue over long distances. One of the mechanisms the team studied earlier is based on the protein reggie-1/fotillin-2.

"It turned out that RPS12 plays a similar role. Thus, we have unveiled a new mechanism for controlling the production of active forms of WNT, and suggest that the RPS12 protein may become a new potential target for anticancer therapy. Further research will show how this protein is really suitable for therapeutic targeting", concluded Vladimir Katanaev.

About 70-80 percent of the genes responsible for human disease have orthologous genes in Drosophila. Evolutionary, these are practically the same genes, but with some individual sequences in humans and fruit flies.

The Drosophila eye development is complex and multistage. At various phases of its development, various signaling pathways and cellular mechanisms one knows in humans become active. Based on this, scientists assumed that any human oncogene, if "transplanted" into the eye of a Drosophila, would lead to a disruption in the development of this organ. A fly with an affected eye lives up to maturity, meaning that it is easy to observe the eye developmental disorders, simply by studying the insect through a microscope.

Scientists started the HumanaFly project more than 10 years ago at the Institute of Protein Research (Pushchino, Russia) in order to find new human oncogenes via the fruit fly eye screening platform. The final experiments of the first phase were carried out in 2020. An extensive genetic library has been formed for the subsequent search for components and mechanisms implicated in the development of cancer.

Scientists at Tokyo Institute of Technology (Tokyo Tech) produced and extensively characterized novel organic molecules with a long helical structure. Unlike previous helical molecules, these longer compounds exhibit special interactions between coils that could give rise to interesting optical and chemical properties with applications in light polarization, catalysis, and molecular springs.

More often than not, organic molecules with unique 3D structures bear physicochemical properties that cannot be found in other types of compounds. Helicenes, chains of simple benzene rings that adopt a helical structure, are a good example. These molecules, which resemble a spring, have interesting applications in optics and as chemical sensors or catalysts. However, it is still difficult to synthesize long helicenes; the longest one ever made was sixteen benzene rings long, which amounted to a helical structure with slightly more than two full turns and a half.

In a recent study published in Chemistry - A European Journal, a team of scientists at Tokyo Tech mixed things up by synthesizing a different type of organic molecule with a helical structure. Unlike helicenes, the basic unit of their compounds was anthracene, a linear chain of three aromatic rings (see Figure 1). In previous works, the team had managed to synthesize [3]HA, which stands for "helical anthracene with three anthracene units." However, as Professor Shinji Toyota, the corresponding author of the study, explains, "[3]HA was not long enough to reach a full turn. Therefore, it did not exhibit some of the peculiar characteristics that arise from the interactions between different 'layers' of the helical structure in a face-to-face fashion."

Using a carefully planned step-by-step process, the scientists managed to synthesize [4]HA and [5]HA, which they proceeded to characterize through a variety of experiments backed by theoretical calculations. They verified the composition and structure of the compounds using proton nuclear magnetic resonance and X-ray analysis. These findings were confirmed through density functional theory calculations, a widely used approach used to make quantum mechanical models of electronic and nuclear structures.

Then, the researchers quantified the stability of the different helical anthracenes by using them in a virtual chemical reaction that changed them into flat molecules. Interestingly, the stability of 3[HA] was almost the same as that of [4]HA and [5]HA. This indicates that the destabilizing forces that naturally appear in longer molecular chains ([4]HA and [5]HA) actually cancelled out with the new face-to-face stabilizing interactions between different helical layers. These interactions between layered anthracene moiety was visualized by Non-Covalent Interaction (NCI) analysis (Figure 32). The effect of these new interactions was also apparent in the photoemission properties of the longer molecules; their emission bands upon excitation were longer-lived, highlighting the fact that excited states were preserved longer.

Finally, the scientists explored the helical inversion process in the new, longer compounds. This inversion refers to the process of left-handed spirals changing into right-handed ones and vice versa. Some attractive optical properties such as circular polarization are lost if left- and right-handed spirals are present in equal proportion. This motivated the team to analyze the stepwise process by which each helical structure changes directions.

Overall, this study provides some much-needed insight into a new type of helical molecule. Already looking ahead, Toyota comments on future works involving these exciting compounds: "Extending helical anthracenes further and producing them with a single coiling direction remains a challenge, and so does testing their performance as molecular springs. Our team is currently working on synthesizing even longer molecules and performing structural modifications." Only time will tell what's in line for helical structures when longer ones finally spring up!

East Hanover, NJ. January 29, 2021. A team of New Jersey researchers has demonstrated that high-dose therapy gait training using robotic exoskeletons may aid early rehabilitation for acute stroke. The article, "Robotic exoskeleton gait training during acute stroke inpatient rehabilitation" (doi: 10.339/fnbot.2020.581815), was published October 30, 2020 in Frontiers in Neurorobotics is available open access at: https://www.frontiersin.org/articles/10.3389/fnbot.2020.581815/full

The authors are Karen Nolan, PhD, Kiran Karunakaran, PhD, and Kathleen Chervin, of Kessler Foundation, Michael Monfett, MD, of Skyline Physical Medicine and Rehabilitation, Radhika Bapineedu, MD, and Neil N. Jasey Jr, MD, of Kessler Institute for Rehabilitation, and Mooyeon Oh-Park, MD, of Burke Rehabilitation Hospital, formerly with Kessler. Drs. Nolan and Karunakaran are also affiliated with Children's Specialized Hospital. Kessler scientists and clinicians have faculty appointments at Rutgers New Jersey Medical School.

The need for stroke rehabilitation is tremendous, given the large numbers of stroke survivors with deficits in mobility, balance and coordination that limit their activities of daily living. Advances in robotics and biomedical engineering are expanding the options for rehabilitative care. Researchers are applying new technologies to gait training that may offer advantages over traditional labor intensive physical therapy. This inpatient study of a robotic exoskeleton (Ekso GT, Ekso Bionics, Inc,) demonstrated the potential to improve gait training after acute stroke toward the goal of earlier recovery of motor function.

Participants included 44 individuals (ages 18 to 82 years) admitted to Kessler Institute for Rehabilitation for acute stroke. Half received conventional standard of care (SOC), and half received SOC with an option for overground gait training in the Ekso GT (RE+SOC). Both groups received the same amount of overall therapy time. Overground gait training in the exoskeleton was supervised by a licensed physical therapist who adjusted the variable bilateral assistance of the Ekso GT according to each individual's progress. Outcome measures were total distance walked during inpatient rehabilitation and functional independence measure (FIM) score. The RE-SOC group trained in the Ekso GT at least three times during their stay.

"We found that gait training in the exoskeleton allowed us to increase the dose of gait training without increasing the duration of inpatient rehabilitation," said Dr. Nolan, assistant director of the Center for Mobility and Rehabilitation Engineering Research at Kessler Foundation. "Because overground walking in the exoskeleton requires active effort on the part of the participant," she added, "early intervention with this type of gait training promotes brain plasticity that may lead to greater functional improvements and more lasting effects when combined with conventional training."

In the treatment of SARS-CoV-2, the virus that causes COVID-19, antiviral drug remdesivir has emerged as a promising candidate.

Remdesivir works by disrupting the virus's ability to replicate, but its exact mechanism has remained a mystery. Using advanced computational simulations, researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have revealed just how the drug works at the molecular level. They also found that two drugs that work in a similar manner, ribavirin and favilavir, do not bind as effectively to the virus.

"It's important to understand how remdesivir works at a molecular level," said Prof. Juan de Pablo, who led the research. "Now that we see that it is effective, and other drugs are not as effective, it can guide future efforts for treating COVID-19."

The results were published Jan. 6 in the journal ACS Central Science.

Understanding how drugs disrupt the virus

Remdesivir works by disrupting SARS-CoV-2's RNA polymerase, a key enzyme that the virus needs to replicate itself. When this enzyme is disrupted, the virus cannot multiply and spread within the body.

But in patients, the drug has produced varied results. Some clinical trials have shown that patients who received it recovered faster and had improved mortality rates, while other trials have shown that the drug did not reduce mortality or hospitalization lengths.

Since the beginning of the pandemic, de Pablo and his group have been using advanced computational simulations to systematically look at the different proteins that allow the virus to replicate or infect cells. They also have looked at the key candidate drugs that are already used to treat other diseases and could be repurposed to inhibit those processes in SARS-CoV-2. The simulations, which require months of extremely powerful computations, ultimately reveal what happens at the molecular level.

To better understand how treatments disrupt the RNA polymerase, de Pablo and his group simulated the interaction between the enzyme and three drugs that are already available, and that are meant to inhibit it: remdesivir, ribavirin, and favilavir. They found that remdesivir binds strongly to the virus, but ribavirin and favilavir do not bind as effectively. They also found that remdesivir destabilizes the virus's protein complex, also reducing its ability to replicate.

Now that simulations show that the drug should work at a molecular level, scientists could focus, for example, on finding better strategies to deliver the drug more effectively, de Pablo said.

A complete landscape of molecular targets

Previously, the group used computational analysis to reveal how the drug Ebselen binds to the virus' main protease, or MPro. Now, the group is also examining the mechanisms of a different set of drugs on different proteins, with the goal of creating a complete landscape of molecular targets.

"We've seen that the virus is not going away and is in fact starting to mutate," de Pablo said. "Efforts to find the best therapies, and the best ways to administer them, have to continue."

Parents know the scenario all too well: their child misbehaves and it comes time for discipline.

Research conducted globally shows that spanking is not the best option. But verbal reasoning, which explains why the behavior is wrong, may not always have the intended positive effect if the parent is loud and abrupt, according to a new University of Michigan study.

The findings indicate both positive and negative outcomes that could have lasting consequences on children's emotional development. Verbal reasoning was associated with higher levels of getting along with others, but also with increased aggression and higher levels of distraction.

"Positive discipline doesn't always seem to have all that many positive benefits," said Andrew Grogan-Kaylor, professor of social work and lead author of the study published in the latest issue of International Journal of Behavioral Development.

"It's more likely that the long-term investments that parents make in children, such as spending time with them, letting them know they are loved and listening to them, have more positive effects than nonviolent discipline. This has yet to be thoroughly researched in a global context."

Research has continually shown that spanking leads to negative child outcomes, such as aggression and distraction, regardless of the context in which children are disciplined, including country, race and ethnicity, and neighborhood.

In the new study, researchers at U-M's Ann Arbor and Flint campuses analyzed different forms of punishment associated with children's behaviors in a global sample of nearly 216,000 families from 62 countries. The data came from the United Nations Children's Fund Multiple Indicator Cluster Surveys.

The results confirmed that spanking was not associated with children getting along with their counterparts. It also led to increased aggression and distraction. For nonviolent discipline, which involved verbal reasoning and taking away privileges, mixed outcomes occurred, Grogan-Kaylor said.

Verbal reasoning did promote one positive result: Children were more prosocial with others, especially in countries where this discipline was more common. Surprisingly, verbal reasoning also increased aggression, likely in cases when the parents used harsh tones and language, the study suggested.

"Verbal reasoning may have negative effects on children if it is not employed in a way that is developmentally appropriate for the child to understand why their behavior is inappropriate," Grogan-Kaylor said.

Meanwhile, children did not get along with other children and showed higher levels of aggression and became distracted when parents took away privileges.

So what's the best way to discipline a child? Grogan-Kaylor suggested providing them structure, keeping the lines of communication open and providing developmentally appropriate removal of privileges.