Culture

Mystery canine illness identified

image: Vets were asked for help in collecting data.

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Lancaster University

An outbreak of vomiting among dogs has been traced back to a type of animal coronavirus by researchers.

Vets across the country began reporting cases of acute onset prolific vomiting in 2019/20.

The Small Animal Veterinary Surveillance Network (SAVSNet) at the University of Liverpool asked vets for help in collecting data, with 1,258 case questionnaires from vets and owners plus 95 clinical samples from 71 animals.

Based on this data, a team from the universities of Liverpool, Lancaster, Manchester and Bristol identified the outbreak as most likely to be a variant of canine enteric coronavirus (CeCoV).

Canine coronavirus only affects dogs and is not the same as Sars Cov2 which causes Covid in humans. Researchers found no evidence of any similar illness in people.

The work is published in Emerging Infectious Diseases.

The team are working on a project funded by the Dogs Trust called SAVSNet-Agile which aims to develop a national surveillance system for canine health.

Dr Barry Rowlingson from Lancaster University said: "We've developed complex statistical models to look for disease outbreaks. Being able to rapidly detect increased incidence, without triggering a false alarm from a natural random variation, is the key problem here. Early detection is crucial to early treatment and enhanced monitoring.

"The SAVSNet Agile project aims to feed information back to local veterinary practices so they can be alert to any new outbreaks."

Vets began to suspect an infectious cause because vomiting was more frequent than is typical for canine gastroenteritis.

SAVSNet researchers found a specific and significant increase in the number of dogs recorded as exhibiting gastroenteric signs between late December 2019 and March 2020.

As well as reusing health records, SAVSNet also collected questionnaire data from vets and owners caring for affected animals, as well as healthy controls. This showed male dogs were more at risk than females.

Charlotte Appleton, SAVSNet Agile PhD Student, said: "Obtaining such important results at an early stage of my PhD is a wonderful achievement and will hopefully provide a pathway of higher visibility into the health of domestic animals."

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Lancaster University

Get your head in the game -- One gene's role in cranial development

image: Proposed regulatory molecular cascades in the initial layer of the calvarium (early migrating mesenchyme: EMM) at E11.5 in the wild-type mouse (a) and the mouse in which Dlx5 is overexpressed in NCC (NCCDlx5: b). ac, activator; in, inhibitor.

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Department of Molecular Craniofacial Embryology,TMDU

Researchers from Tokyo Medical and Dental University (TMDU) use genetic engineering in mice to further understand how cell fate is determined in the head

Tokyo, Japan - Mammalian embryonic development is an extremely complex and precise process. Specific molecular events act as cues that tell cells in the embryo where to move and what type to mature into. The expression levels of different genes in these cells can change at certain points of development, helping produce the signals that further the progression. Now, researchers at Tokyo Medical and Dental University (TMDU) have used experiments with mice to show how a particular gene helps direct generation of tissues in the head.

In an article published in Scientific Reports, a group of researchers from TMDU determined that expression of a gene called Distal-less homeobox 5 (Dlx5) assists certain cells in the mouse head mature into cartilage cells, while others become bone cells. This is critical for proper cranial formation.

Neural crest cells (NCCs) have been a recent focus of developmental biology research because they can transition into many cell types including neurons, and those in the head region additionally differentiate into bone and cartilage. NCCs form an initial layer that constructs dermis and the meninges in early stages of development, then another group of NCCs present at the supraorbital region becomes bone forming cells and the cell domain expands apically as the overlying layer to form the calvarium to protect the brain. From these previous observations, the TMDU group became interested in how experimentally increasing Dlx5 expression would affect NCC differentiation.

"We worked with a mouse model to further understand how over-expressed Dlx5 affects cranial development," says lead author of the study Tri Vu Hoang. "We used a method where we could force higher expression levels of Dlx5 in NCCs in a group of mice, then compared their head development with mice not genetically engineered in this way."

The researchers first confirmed that Dlx5 was being expressed in NCCs in the engineered moue as they expected before examining cranial bone and cartilage formation in the two groups of mice. They observed enhanced layers of both bone and cartilage in the mice with higher NCC Dlx5 expression compared with the controls.

"We saw an interesting response with Dlx5 overexpression in the NCCs," describes Sachiko Iseki, senior author. "NCCs intrinsically forming soft tissues of the initial layer transform into bone and cartilage in the vertex of the Dlx5-engineered mice."

The group also examined expression of several bone and cartilage growth-promoting genes in the regions where new cartilage and bone were formed. They observed upregulation of multiple major genes for bone and cartilage formation including β-catenin and Pdgfrα, bone genes were expressed in the region close to the skin and cartilage genes near the brain in the Dlx5-engineered mice that was not seen in the control animals. The observation shows that the initial soft tissue layer transform into the two different layers around the time of bone and cartilage formation.

"Our results shed light on early development of the head layer of NCCs in the mouse vertex; there two cell layers exhibiting differentiating potential for bone and cartilage." says Vu Hoang. "Overexpression of Dlx5 in NCCs is an artificial situation in embryonic development, but it showed us an interesting phenomenon to discuss uncovered developmental mechanisms in the vertex of the head."

This study provides fascinating data that will help move the developmental biology field forward. The researchers have successfully helped reveal the complicated mechanisms involved with cranial development.

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Tokyo Medical and Dental University

Novel diabetes subgroups show differences in biomarkers of inflammation

Chronic inflammation is increasingly a focus of research. A recent study has now identified differences in indicators of inflammation between novel diabetes subgroups. But what does this mean for the future?

Symptoms that increase with age, such as cardiovascular disease, kidney damage or dementia, are common consequences of type 2 diabetes. In addition to metabolic disorders, chronic inflammatory reactions are important causes. The inflammatory cytokines typical for this can have numerous effects on various organs. One of the consequences of this is that the organs no longer respond adequately to insulin.

A new analysis of the German Diabetes Study (GDS) from the German Diabetes Centre (DDZ) investigated the differences between individual diabetes subgroups in the biomarkers of inflammation. Biomarkers are indicators that occur in the blood or in tissue and other parts of the body and are typical for certain changes in the body such as inflammation. In the current study, 74 biomarkers covering a broad spectrum of inflammatory processes were measured in over 400 test persons. The result: the novel diabetes subgroups show a number of specific differences that could allow a better determination of the risk for diabetes-related complications.

The German Diabetes Study (GDS) previously made it possible to identify five subgroups (clusters) of diabetes with different courses: severe autoimmune diabetes (SAID), severe insulin deficient diabetes (SIDD), severe insulin resistant diabetes (SIRD), moderate obesity-related diabetes (MOD) and moderate age-related diabetes (MARD). The current study shows that these subgroups differ not only in terms of age and metabolic characteristics, but also in terms of biomarkers of inflammation. Given the critical role of inflammatory processes in diabetes-related complications, these differences may also be related to the severity of clinical courses of diabetes. "It is interesting that this study of people with newly diagnosed diabetes reveals early disorders and can thus contribute to the early detection of diabetes consequences," said Professor Michael Roden, scientific director and board member of the DDZ. "As a result, these findings could enable early therapy in individual diabetes subgroups."

The highest biomarker blood levels were observed in the diabetes subgroup SIRD, which is characterized by pronounced insulin resistance. This underlines the importance of overweight/obesity, which is particularly related to inflammation and insulin resistance. On the other hand, the SIDD subgroup, which is mainly characterized by insulin deficiency, had the lowest biomarker levels. "This correlation between high levels of inflammatory markers and pronounced insulin resistance indicates a particular contribution of inflammatory processes in the SIRD subgroup," said Dr. Christian Herder, who heads the Inflammation working group at the DDZ. "It will take a few more years before we can derive a specific recommendation for diabetes therapy from these findings, but the results are extremely relevant for diabetes complications and their understanding. Future studies are needed to investigate to what extent differences in the profiles of inflammation-related biomarkers can explain the differences between the diabetes subgroups in terms of their risk of developing diabetes-related complications."

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Deutsches Zentrum fuer Diabetesforschung DZD

Superbug killer: New nanotech destroys bacteria and fungal cells

image: A fungal cell (green) interacting with a nanothin layer of black phosphorous (red). Image magnified 25,000 times.

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RMIT University

Researchers have developed a new superbug-destroying coating that could be used on wound dressings and implants to prevent and treat potentially deadly bacterial and fungal infections.

The material is one of the thinnest antimicrobial coatings developed to date and is effective against a broad range of drug-resistant bacteria and fungal cells, while leaving human cells unharmed.

Antibiotic resistance is a major global health threat, causing at least 700,000 deaths a year. Without the development of new antibacterial therapies, the death toll could rise to 10 million people a year by 2050, equating to $US100 trillion in health care costs.

While the health burden of fungal infections is less recognised, globally they kill about 1.5 million people each year and the death toll is growing. An emerging threat to hospitalised COVID-19 patients for example is the common fungus, Aspergillus, which can cause deadly secondary infections.

The new coating from a team led by RMIT University in Melbourne, Australia, is based on an ultra-thin 2D material that until now has mainly been of interest for next-generation electronics.

Studies on black phosphorus (BP) have indicated it has some antibacterial and antifungal properties, but the material has never been methodically examined for potential clinical use.

The new research, published in the American Chemical Society's journal Applied Materials & Interfaces, reveals that BP is effective at killing microbes when spread in nanothin layers on surfaces like titanium and cotton, used to make implants and wound dressings.

Co-lead researcher Dr Aaron Elbourne said finding one material that could prevent both bacterial and fungal infections was a significant advance.

"These pathogens are responsible for massive health burdens and as drug-resistance continues to grow, our ability to treat these infections becomes increasingly difficult," Elbourne, a Postdoctoral Fellow in the School of Science at RMIT, said.

"We need smart new weapons for the war on superbugs, which don't contribute to the problem of antimicrobial resistance.

"Our nanothin coating is a dual bug killer that works by tearing bacteria and fungal cells apart, something microbes will struggle to adapt to. It would take millions of years to naturally evolve new defences to such a lethal physical attack.

"While we need further research to be able to apply this technology in clinical settings, it's an exciting new direction in the search for more effective ways to tackle this serious health challenge."

Co-lead researcher Associate Professor Sumeet Walia, from RMIT's School of Engineering, has previously led groundbreaking studies using BP for artificial intelligence technology and brain-mimicking electronics.

"BP breaks down in the presence of oxygen, which is normally a huge problem for electronics and something we had to overcome with painstaking precision engineering to develop our technologies," Walia said.

"But it turns out materials that degrade easily with oxygen can be ideal for killing microbes - it's exactly what the scientists working on antimicrobial technologies were looking for.

"So our problem was their solution."

How the nanothin bug killer works

As BP breaks down, it oxidises the surface of bacteria and fungal cells. This process, known as cellular oxidisation, ultimately works to rip them apart.

In the new study, first author and PhD researcher Zo Shaw tested the effectiveness of nanothin layers of BP against five common bacteria strains, including E. coli and drug-resistant MRSA, as well as five types of fungus, including Candida auris.

In just two hours, up to 99% of bacterial and fungal cells were destroyed.

Importantly, the BP also began to self-degrade in that time and was entirely disintegrated within 24 hours - an important feature that shows the material would not accumulate in the body.

The laboratory study identified the optimum levels of BP that have a deadly antimicrobial effect while leaving human cells healthy and whole.

The researchers have now begun experimenting with different formulations to test the efficacy on a range of medically-relevant surfaces.

The team is keen to collaborate with potential industry partners to further develop the technology, for which a provisional patent application has been filed.

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RMIT University

Lower COVID-19 rates seen in US states with higher adherence to mask wearing

A new state-by-state analysis shows a statistical association between high adherence to mask wearing and reduced rates of COVID-19 in the U.S. Charlie Fischer and colleagues at the Boston University School of Public Health in Massachusetts present these findings in the open-access journal PLOS ONE on April 14.

During the COVID-19 pandemic, different states have enacted different policies on mask wearing, with some states having no mask requirements and others requiring masks in all public spaces. Understanding the link between mask wearing and COVID-19 rates could help inform policies to mitigate stress on healthcare systems, economic instability, and death.

To help clarify the effects of mask wearing, Fischer and colleagues examined publicly available data on mask-wearing policies, people's self-reported habits on mask wearing in public, and COVID-19 rates for all 50 U.S. states and Washington, D.C. They accounted for a one-month delay between mask wearing and its subsequent potential impact on COVID-19 rates from May through October 2020. For this analysis, they considered rates of more than 200 cases per 100,000 residents to be high.

The analysis showed that, out of 15 states that did not require people to wear masks in public, 14 had high COVID-19 rates. Meanwhile, eight states had self-reported adherence rates of 75 percent of greater, and none of these states had a high COVID-19 rate. States with the lowest adherence rates had the greatest likelihood of high COVID-19 rates in the subsequent month.

The eight states with at least 75-percent adherence to mask wearing had a mean COVID-19 rate of 109.26 per 100,000 residents in the subsequent month, while the mean COVID-19 rate was 239.99 for states with less than 75 percent adherence.

These findings provide new evidence in support of mask-wearing as a major factor that contributes to reduced COVID-19 rates. They suggest that policies and public health efforts to reduce the spread of COVID-19 should include a focus on improved mask adherence throughout the U.S.

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PLOS

The Lancet Infectious Diseases: First clinical evidence of drug-resistant malaria mutations gaining

- Study finds for the first time, in Africa, that mutations are associated with delayed clearance of the parasite among children with malaria treated with common Artemisinin-based combination therapies (ACTs).

- While drug efficacy remains high so far, authors call for increased monitoring in the region.

New data provide the first clinical evidence that drug-resistant mutations in the malaria parasite Plasmodium falciparum may be gaining a foothold in Africa. The study, conducted in Rwanda, is published in The Lancet Infectious Diseases journal and finds for the first time that the mutations are associated with delayed parasite clearance, as was first shown in South-East Asia when artemisinin-resistance started to emerge.

The study also finds that the mutations are more prevalent than previous studies have reported, indicating likely transmission of the mutations, and raising concern about further geographical spread of resistance.

There are an estimated 229 million cases of malaria worldwide, and there were 409,000 deaths from malaria in 2019 - of which 274,000 (67%) were among children under 5 years. 94% of all malaria cases and deaths occur in Africa [1], and experts have long been concerned about the potential emergence of drug resistance across the continent. While the efficacy of current therapies remains high, the authors call for more intensive surveillance in Rwanda as well as neighbouring countries to help monitor the spread of mutations and inform public health actions.

"Mutations can emerge spontaneously, and previous studies have pointed to isolated cases of resistance. However, our new study shows that resistant isolates are starting to become more common and most importantly, are associated with clinical implications (delayed parasite clearance)," says lead author Dr Aline Uwimana, Rwanda Biomedical Centre, Kigali, Rwanda [2]

Co-author Dr Naomi Lucchi, CDC Resident Advisor for the U.S. President's Malaria Initiative adds: "our study showed that the treatment for malaria in Rwanda is still 94% effective, but new studies and ongoing monitoring are urgently needed." [2]

Artemisinin-based combination therapies (ACTs), introduced in the early 2000s, are currently the most effective and widely used treatments for malaria caused by Plasmodium falciparum. ACTs combine an artemisinin component that clears most of the parasites from the patient's body within three days, and a long-acting partner drug that clears the remaining parasites.

Resistance to the artemisinin component of an ACT is suspected if the presence of the parasite remains after day three of treatment (called delayed parasite clearance). This drug resistance is associated with parasites carrying mutations in the Plasmodium falciparum kelch 13 gene (pfk13). Currently, ten mutations in pfk13 have been confirmed as markers of artemisinin partial resistance (including R561H, P574L and C580Y), and several other mutations (referred to as candidate markers) have been identified as potentially associated with resistance.

Partial artemisinin resistance was first identified in Cambodia in 2008. It is now well-documented in many South East Asian countries, where the C580Y mutation is common. Evidence from the Mekong region has shown that once artemisinin resistance becomes prevalent, resistance to the partner drug often follows, resulting in ACT treatment failure.

In 2006, Rwanda introduced artemether-lumefantrine (an ACT, and the most widely used antimalarial) as the first-line treatment for malaria. The World Health Organization recommends therapeutic efficacy studies at least every two years for monitoring the efficacy of ACTs and the tracking of resistance through molecular markers. When ACT efficacy is confirmed to be below 90%, replacement with an effective antimalarial is recommended.

One such study was performed in Rwanda among children aged 1-14 years in 2013-2015 in Ruhuha and Masaka. The R561H mutation was observed in 7.4% of P. falciparum parasites collected in Masaka, and a low prevalence of the P574L mutation was reported in isolates collected in Masaka and Ruhuha in 2013-2015 and in Huye in 2015. However, the presence of these mutations was not found to be associated with delayed parasite clearance and the therapeutic efficacy of ACT was confirmed at over 97% in both sites.

In 2018, another therapeutic efficacy study was conducted, the results of which are reported in this new article. The pfk13 R561H and P574L mutations were present in 12.8% (28/218) and 0.9% (2/218) of pre-treatment samples, respectively. For the first time, this study shows that the pfk13 R561H mutation was associated with delayed parasite clearance, although the efficacy of artemether-lumefantrine remained high. Genetic analysis of pfk13 R561H mutants indicated their common ancestry and local origin in Rwanda.

The study was conducted across three sites in Rwanda (Masaka, Rukara, and Bugarama). 224 children aged between 6 months and 5 years who had a P. falciparum infection were treated with a three-day course of artemether-lumefantrine and monitored for 28 days, with weekly blood collections. 8/51 (15.7%) participants in Masaka and 12/82 (14.6%) in Rukara had detectable parasites three days post treatment, according to WHO criteria for partial resistance. The therapeutic efficacy was estimated at 94-97%.

Writing in a linked Comment, Professor Philip Rosenthal, University of California, San Francisco, USA (who was not involved in the study), says: "Recent data suggest that we are on the verge of clinically meaningful artemisinin resistance in Africa, as emerged in Southeast Asia over a decade ago. With resistant genotypes emerging and continued heavy drug pressure, we may anticipate continued selection of resistance. Loss of artemisinin activity will in turn threaten ACT partner drugs. Loss of efficacy of key ACTs, in particular artemether-lumefantrine, the most widely used antimalarial, may have dire consequences, as occurred when chloroquine resistance led to enormous increases in malaria deaths in the late twentieth century. Although it is impossible to predict the pace of progression of drug resistance in Africa, close surveillance for genotypic and phenotypic evidence of artemisinin and partner drug resistance, with prompt replacement of failing regimens, may save many lives."

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The Lancet

Study identifies ways women increase their sexual pleasure during vaginal penetration

image: Researchers from Indiana University School of Medicine and OMGYES have conducted the first-ever, large-scale, nationally representative study focused on women's techniques for increasing their own pleasure from vaginal penetration. The findings, published today in the scientific journal, PLOS ONE, identify and name four distinct methods: Angling, Pairing, Rocking and Shallowing.

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OMGYES

INDIANAPOLIS, IN AND BERKELEY, CA (April 14, 2021) - Researchers from Indiana University School of Medicine and OMGYES have conducted the first-ever, large-scale, nationally representative study focused on women's techniques for increasing their own pleasure from vaginal penetration. The findings, published today in the scientific journal, PLOS ONE, identify and name four distinct methods: Angling, Pairing, Rocking and Shallowing.

The research was led by Dr. Devon J. Hensel, Associate Professor of Research at Indiana University School of Medicine, and Dr. Christiana von Hippel, an OMGYES Research Scientist.

"For the first time, we have detailed scientific data to understand the different ways that women experience more pleasure with vaginal penetration. This information can help us build a vocabulary to describe female pleasure that currently doesn't exist," explains Dr. Hensel.

"When something doesn't even have a name, it's made literally unspeakable," said Dr. von Hippel. "Until now, there haven't been words for the specific ways women improve their pleasure. By giving these prevalent techniques names and showing how they can be effective, we hope women will be empowered to explore what they like and advocate for what they want, in and outside of the bedroom."

To begin, the researchers gathered discoveries and insights from a community of 4,270 women from around the world and analyzed the results to find themes and underlying patterns. These qualitative findings then informed the quantitative, cross-sectional, nationally representative survey fielded online with 3,017 American women, ages 18-93.

The findings, described in depth in the paper and highlighted below, reveal four distinct ways women have discovered to experience more pleasure during vaginal penetration:

Rocking - 76.4% of women make penetration more pleasurable by 'rocking' the base of a penis or sex toy so it rubs against the clitoris constantly during penetration, staying all the way inside the vagina rather than thrusting in and out.

Angling - 87.5% of women experience more pleasure during penetration by 'angling' which involves rotating, raising, or lowering the pelvis/hips during penetration to adjust where inside the vagina the toy or penis rubs, and what it feels like.

Pairing - 69.7% of women find penetration more pleasurable when 'pairing' where a woman herself (solo pairing) or her partner (partner pairing) reaches down to stimulate the clitoris with a finger or sex toy at the same time as the vagina is being penetrated.

Shallowing - 83.8% of women orgasm more often or increase their pleasure through 'shallowing,' penetrative touch just inside the entrance of the vagina with a fingertip, sex toy, penis tip, tongue or lips.

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OMGYES

Cultivating Matsutake, valuable edible fungi

image: Three T.matsutake specimens used for the spore inoculation experiment.

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Copyright © 2021, Akiyoshi Yamada et al., under exclusive license to Springer-Verlag GmbH Germany, part of Springer Nature

Costing anywhere from 15 to 70 dollars per mushroom depending on the quality, matsutake mushrooms are some of the most valuable edible fungi in the world. Revered for their delicate scent, matsutake mushrooms are cooked in rice or soups as an Autumn celebration delicacy in Japan. However, there is no way to cultivate matsutake mushrooms and naturally occurring habitats are decreasing with fewer forests conducive to their growth with the changing climate.

Corresponding author Professor Akiyoshi Yamada of Shinshu University's Department of Agriculture, Department of Bioscience and Biotechnology, and Institute for Mountain Science with 9 other researchers set out to present concrete evidence that matsutake spores germinate, reach the roots of the host, and coexist to produce offspring that starts a new symbiosis.

When matsutake spores germinate, mycelia in the soil corresponding to their parents induce germination and form a genetically diverse population on the root system of the host. It is therefore hypothesized that the next generation can be created while maintaining a diverse pool.

With this novel experiment, matsutake mushrooms and Japanese red pine were cultured in a vessel, and spores collected from the fruiting bodies of matsutake mushrooms collected outdoors were inoculated to germinate in order to successfully establish a new hypha in the roots of Japanese red pine.

The researchers were successful in germinating the spore of matsutake by proving that artificially controlling the phenomenon of generational change of matsutake mushrooms in the natural world. They hope to establish an artificial cultivation technique for matsutake mushrooms in the forest.

Since this study introduces fresh matsutake spores into the experimental system, it is difficult to carry out this study unless there is a supply of matsutake nearby. In other words, it can be said that this research finding best utilized the location of the Faculty of Agriculture, Shinshu University to germinate the spore of matsutake, the most valuable wild edible mushrooms in the world.

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Shinshu University

3D-printed material to replace ivory

image: On the right: The new material Digory, ivory on the left

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TU Wien

For centuries, ivory was often used to make art objects. But to protect elephant populations, the ivory trade was banned internationally in 1989. To restore ivory parts of old art objects, one must therefore resort to substitute materials - such as bones, shells or plastic. However, there has not been a really satisfactory solution so far.

TU Wien (Vienna) and the 3D printing company Cubicure GmbH, created as a spin-off of TU Wien, have now developed a high-tech substitute in cooperation with the Archdiocese of Vienna's Department for the Care of Art and Monuments and Addison Restoration: the novel material "Digory" consists of synthetic resin and calcium phosphate particles. It is processed in a hot, liquid state and hardened in the 3D printer with UV rays, exactly in the desired shape. It can then be polished and colour-matched to create a deceptively authentic-looking ivory substitute.

Beautiful and Mechanically Stable

"The research project began with a valuable 17th-century state casket in the parish church of Mauerbach," says Prof. Jürgen Stampfl from the Institute of Materials Science and Technology at TU Wien. "It is decorated with small ivory ornaments, some of which have been lost over time. The question was whether they could be replaced with 3D printing technology."

The team already had experience with similar materials: the research group also works with ceramic materials for dental technology, for example. Nevertheless, it was a challenging task to develop a suitable substitute for ivory: "We had to fulfil a whole range of requirements at the same time," says Thaddäa Rath, who worked on the project as part of her dissertation. "The material should not only look like ivory, the strength and stiffness must also be right, and the material should be machinable."

Stereolithography in the 3D printer

Through numerous experiments, Thaddäa Rath and other members of the team from TU Wien and Cubicure succeeded in finding the right mixture: Tiny calcium phosphate particles with an average diameter of about 7 μm were embedded in a special resin, together with extremely fine silicon oxide powder. The mixture is then processed at high heat in Cubicure's 3D printers using the hot lithography process: Layer by layer, the material is cured with a UV laser until the complete object is finished.

"You also have to bear in mind that ivory is translucent," explains Thaddäa Rath. "Only if you use the right amount of calcium phosphate will the material have the same translucent properties as ivory." Afterwards, the colour of the object can be touched up - the team achieved good results with black tea. The characteristic dark lines that normally run through ivory can also be applied afterwards with high precision.

No more tusks!

In the field of restoration, this is a big step forward: With the new material "Digory", not only is a better, more beautiful and easier to work with substitute for ivory available than before, the 3D technology also makes it possible to reproduce the finest details automatically. Instead of painstakingly carving them out of ivory substitute material, objects can now be printed in a matter of hours.

"With our specially developed 3D printing systems, we process different material formulations for completely different areas of application, but this project was also something new for us," says Konstanze Seidler from Cubicure. "In any case, it is further proof of how diverse the possible applications of stereolithography are."

The team hopes that the new material "Digory" will become generally accepted in the future - as an aesthetically and mechanically high-quality ivory substitute, for which no elephant has to lose a tusk.

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Vienna University of Technology

Are chemical pollutants altering the behaviour of wildlife and humans?

International scientists from around the world are warning that chemical pollutants in the environment have the potential to alter animal and human behaviour.

A scientific forum of 30 experts formed a united agreement of concern about chemical pollutants and set up a roadmap to help protect the environment from behaviour altering chemicals. The conclusions of their work have been published today in a paper led by Professor Alex Ford, Professor of Biology at the University of Portsmouth, in Environmental Science and Technology. Until now the effect of chemical pollutants on wildlife has been studied and risk assessed in relation to species mortality, reproduction and growth. The effect on behaviour has been suspected but never formally tested or assessed - the scientists say this needs to change.

The world leading experts came from a variety of relevant disciplines including environmental toxicology, regulatory authorities and chemicals risk assessors. Professor Alex Ford explains: "The group were in no doubt that pollution can impact the behaviour of humans and wildlife. However, our ability to regulate chemicals for these risks, and therefore safeguard the environment, is rarely used. For example, chemicals that are deliberately designed as pharmaceutical drugs to alter behaviour, such as antidepressants and antianxiety medications, have been shown to alter the behaviours of fish and invertebrates during laboratory experiments. These medications like many prescribed drugs enter the environment through wastewaters."

History shows us there are other examples of behavioural alterations from chemicals. During the 19th century, the phrases "Mad as a hatter" and "Crazy as a painter" were coined when those in these trades were found to have changed behaviour, from the use of lead and mercury. In more recent times concerns over metal toxicity resulted in the enforcement of unleaded fuels.

The scientists are not just concerned about the obvious pollutants such pharmaceutical drugs leaking into the environment but they also warn about the potential unknowns such as chemicals in plastics, washing agents, fabrics and personal care products.

The forum have come up with a roadmap they are urging policy makers, regulatory authorities, environmental leaders to act upon.

The recommendations are:

- Improve the mechanisms of how science studies contaminated-induced behavioural changes.

- Develop new and adapt existing standard toxicity tests to include behaviour.

- Develop an integrative approach to environmental risk assessment, which includes behaviour. Not just mortality, growth and reproduction.

- Improve the reliability of behavioural tests, which need to allow for variation in behavioural reactions.

- Develop guidance and training on the evaluation of reporting of behavioural studies.

- Better integration of human and wildlife behavioural toxicology.

Professor Ford said: "We know from human toxicology and pharmaceutical drug development that regulatory authorities and industry have advanced with confidence in the use of behavioural endpoints, either in chemical risk assessment and drug development. We are yet to see this used fully when addressing the health of the environment and the impacts chemicals may have on wildlife behaviours. There is real concern around our lack of knowledge of how pollutants affect wildlife and human behaviour and our current processes for assessing this are not fit for purpose."

Dr Gerd Maack, from the German Environment Agency (UBA) and host of the forum, added: "We know that chemicals affect human and wildlife behaviours, especially hormones are affecting the mating behaviour of vertebrates. However, this knowledge is still not reflected in the regulation of chemicals in Europe, partly due to a lack of standardised methods, but also due to a non-understanding of the more complex study designs by many regulators. As one of the first of its kind, this workshop brought together behavioural scientists and regulators underpinning the importance of behavioural studies for the regulation. The results of this paper will serve a road map for a better acceptance and integration of behaviour studies in regulatory practices."

Joel Allen, from the U.S. Environmental Protection Agency said: "Along with my U.S. EPA colleagues, Jim Lazorchak and Stephanie Padilla, and as participants in the workshop and the preparation of this manuscript, we are excited about being part of a ground-breaking area in the potential use of behavioral responses to chemicals in chemical risk assessments as well as being co-authors on this topic in the prestigious Environmental Science and Technology Journal."

Dr Marlene Agerstrand, an expert of chemicals risk assessment from the University of Stockholm said: "The regulation of chemicals is constantly evolving, as the scientific basis improves. A workshop like this, where researchers and regulators meet, could be the starting point for a change in how behavioural studies are viewed upon in the regulatory sphere. In this paper, we have identified knowledge gaps and regulatory needs with the purpose to continue the discussion with a wider stakeholder group."

The forum took place at the German Environment Agency (UBA).

Credit: 
University of Portsmouth

Expert reviews discuss key topics in bone disorders and chronic kidney disease

Metabolic bone disease is a common complication of chronic kidney disease (CKD) and involves a broad spectrum of disorders of mineral metabolism that result in both skeletal and extra-skeletal consequences.

A new special issue of Calcified Tissue International brings together a comprehensive series of state-of-the-art reviews which discuss key issues in CKD and mineral and bone disorders, known as CKD-MBD. Authored by a multidisciplinary group of leading international experts, the wide-ranging reviews aim to improve the understanding and management of CKD-MBD, and advance interdisciplinary knowledge.

Professors René Rizzoli and Stuart Ralston, Editors of Calcified Tissue International, stated:

"We greatly thank the authors for their contributions and the guest editors Professors J. B Cannata-Andía, N. Carrillo-López, and A. Ferreira, for curating this excellent series of reviews. The special issue brings together multidisciplinary expertise and covers many key topics of great importance to the field. We hope that these contributions will help to foster interaction among the diverse specializations involved in CKD-MBD research and clinical management."

The special issue comprises the following editorial and twelve invited reviews:

1. Editorial: Cannata-Andía, J., Carrillo-López, N. & Ferreira, A. Bone in CKD, a Fascinating Evolving Topic.
Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-021-00821-8

2. Cannata-Andía, J.B., Martín-Carro, B., Martín-Vírgala, J. et al. Chronic Kidney Disease--Mineral and Bone Disorders: Pathogenesis and Management. Calcif Tissue Int (2020). https://doi.org/10.1007/s00223-020-00777-1

3. Santos, F., Díaz-Anadón, L., Ordóñez, F.A. et al. Bone Disease in CKD in Children. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-020-00787-z

4. Carrillo-López, N., Martínez-Arias, L., Fernández-Villabrille, S. et al. Role of the RANK/RANKL/OPG and Wnt/β-Catenin Systems in CKD Bone and Cardiovascular Disorders. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-020-00803-2

5. Mazzaferro, S., Bagordo, D., De Martini, N. et al. Inflammation, Oxidative Stress, and Bone in Chronic Kidney Disease in the Osteoimmunology Era. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-020-00794-0

6. Leal, D.V., Ferreira, A., Watson, E.L. et al. Muscle-Bone Crosstalk in Chronic Kidney Disease: The Potential Modulatory Effects of Exercise. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-020-00782-4

7. Fusaro, M., Cianciolo, G., Evenepoel, P. et al. Vitamin K in CKD Bone Disorders. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-020-00792-2

8. Ferreira, A.C., Cohen-Solal, M., D'Haese, P.C. et al. The Role of Bone Biopsy in the Management of CKD-MBD. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-021-00838-z

9. Komaba, H., Ketteler, M., Cunningham, J. et al. Old and New Drugs for the Management of Bone Disorders in CKD. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-020-00788-y

10. Jørgensen, H.S., David, K., Salam, S. et al. Traditional and Non-traditional Risk Factors for Osteoporosis in CKD. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-020-00786-0

11. Bover, J., Ureña-Torres, P., Cozzolino, M. et al. The Non-invasive Diagnosis of Bone Disorders in CKD. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-020-00781-5

12. Pimentel A et al (2020) Bone fragility fractures in CKD patients. Calcif Tissue Int. https:// doi. org/ 10. 1007/ s00223- 020- 00779-z

13. Torregrosa, JV., Ferreira, A.C., Cucchiari, D. et al. Bone Mineral Disease After Kidney Transplantation. Calcif Tissue Int (2021). https://doi.org/10.1007/s00223-021-00837-0

Credit: 
International Osteoporosis Foundation

Research breakthrough in understanding how neural systems process and store information

Research breakthrough in understanding how neural systems process and store information.

A team of scientists from the University of Exeter and the University of Auckland have made a breakthrough in the quest to better understand how neural systems are able to process and store information.

The researchers, including lead author Dr Kyle Wedgwood from the University of Exeter's Living Systems Institute, have made a significant discovery in how a single cell can store electrical patterns, similar to memories.

They compared sophisticated mathematical modelling to lab-based experiments to determine how different parameters, such as how long it takes for neuronal signals to be processed and how sensitive a cell is to external signals, affect how neural systems encode information.

The research team found that a single neuron is able to select between different patterns, dependent on the properties of each individual stimulus.

The research offers a new step towards developing a greater understanding of how information is encoded and stored in the brain, which could open up fresh insights into the cause and treatment of conditions such as dementia.

The research is published in the Journal of the Royal Society Interface on Wednesday, April 14th 2021.

Dr Wedgwood, from the University of Exeter's Living Systems Institute said: "This work highlights how mathematical analysis and wet-lab experiments can be closely integrated to shed new light on fundamental problems in neuroscience.

"That the theoretical predictions were so readily confirmed in experiments gives us great confidence in the mathematical approach as a tool for understanding how individual cells store patterns of activity. In the long run, we hope that this is the first step to a better understanding of memory formation in neural networks."

According to Professor Krauskopf from the University of Auckland: "The research shows that a living neuron coupled to itself is able to sustain different patterns in response to a stimulus. This is an exciting first step towards understanding how groups of neurons are able to respond to external stimuli in a precise temporal manner.''

"Communication between neurons occurs over large distances. The communication delay associated with this plays an important role in shaping the overall response of a network. This insight is crucial to how neural systems encode memories, which is one of the most fundamental questions in neuroscience,'' adds Professor Tsaneva form the University of Exeter's Living Systems Institute.

Robust spike timing in an excitable cell with delayed feedback is published in the Journal of the Royal Society Interface on Wednesday, April 14th 2021.

Credit: 
University of Exeter

Scientists program microalgae's 'oil factory' to produce various oils

image: Length of fatty acid molecules can be tuned at will, just like the golden cudgel of Monkey King

Image: 
LIU Yang and WANG Qintao

By combining the 'chassis' of an oil-producing microalgae with genes from a Cuphea plant, scientists from the Single-Cell Center, Qingdao Institute of BioEnergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS), can turn the algae into a microbial cell factory that can produce various oils with different properties.

The study was published in Metabolic Engineering on April 3.

Oils are composed of fatty acids, and fatty acids are composed in part of chains of carbon atoms. The length of these carbon chains can impact the physical properties of the fatty acid and thus the property of the oil. The researchers now can program the algal 'factory' by designing the algae to produce fatty acids of different lengths.

Oleaginous microalgae are often attractive candidates as "cell factories" due to their rapid reproduction rates and ability to produce large volumes of fatty acids.

But the chain-length of the fatty acids produced by these self-replicating photosynthetic factories is very rigidly specific to a given species. Typically, one type of microalgae would be great at producing fatty acids of some lengths, but not others.

In microalgae, fatty acids are synthesized by a particular type of enzyme, called the fatty acid synthase, or FAS. And the chain length of these fatty acids is in turn determined by the action of another type of enzyme, called an Acyl-ACP thioesterase, or simply a TE. Different types of TEs from different species specialize in different chain lengths.

"This is far from ideal as a product-flexible cell factory to deliver the plethora of chain lengths needed at will for various industrially relevant fatty acids, as you would have to constantly swap out the species that is doing the producing," said WANG Qintao, a researcher at Single-Cell Center, the first author of the study.

However, the research team found that the microalgae Nannochloropsis oceanica (N. oceanica) had a TE enzyme pathway that can vary the chain length to produce three variations on some of the longer fatty acids, but can't vary the chain length to produce multiple mid-length fatty acids.

So they added the genes for a similar TE enzyme pathway from a Cuphea plant - one that was good at boosting production of fatty acids with those mid-length chains. Protein engineers led by FENG Yanbin and XUE Song, now at Dalian University of Technology, tuned the enzymes so that fatty acids of a different chain length can be produced. The Cuphea genus is home to many species of plants also known for their oil production capabilities.

But by combining the enzymes, the team showed that it was possible to ratchet the fatty acid chain up and down a broad range of desired lengths, and within the N. oceanica 'factory'.

The researchers hope that this basic framework will now accelerate the development of designer oils of various fatty acid chain lengths within other species of Nannochloropsis and other oleaginous microalgae.

"By directly turning CO2, sunlight and seawater into designer oils, such microalgae cell factories are carbon negative, thus farming them at a large scale can help to save our planet from global warming," added XU Jian, Director of Single-Cell Center, and one senior author of the study.

Credit: 
Chinese Academy of Sciences Headquarters

Plasma device designed for consumers can quickly disinfect surfaces

image: Coauthors from top: Philip Efthimion, Yevgeny Raitses, Shurik Yatom, Maria Belen Harreguy and Gal Haspel. Below: Lead author Sophia Gershman.

Image: 
Photos of Efthimion, Raitses, Yatom and Gershman by Elle Starkman/PPPL Office of Communications. Photo of Harreguy by Zainab Tanvir; photo of Haspel courtesy of NJIT. Collage by Elle Starkman with figures from paper.

The COVID-19 pandemic has cast a harsh light on the urgent need for quick and easy techniques to sanitize and disinfect everyday high-touch objects such as doorknobs, pens, pencils, and personal protective gear worn to keep infections from spreading. Now scientists at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory and the New Jersey Institute of Technology (NJIT) have demonstrated the first flexible, hand-held, device based on low-temperature plasma -- a gas that consists of atoms, molecules, and free-floating electrons and ions -- that consumers can quickly and easily use to disinfect surfaces without special training.

Recent experiments show that the prototype, which operates at room temperature under normal atmospheric pressure, can eliminate 99.99 percent of the bacteria on surfaces, including textiles and metals in just 90 seconds. The device has shown a still-higher 99.9999 percent effectiveness when used with the antiseptic hydrogen peroxide. Scientists think it will be similarly effective against viruses. "We're testing it right now with human viruses," said PPPL physicist Sophia Gershman, first author of a paper in Scientific Reports that describes the device and the research behind it.

Positive results welcomed

The positive results were welcome at PPPL, which is widening its fusion research and plasma science portfolios. "We are very excited to see plasmas used for a broader range of applications that could potentially improve human health," said Jon Menard, deputy director for research at PPPL.

The flexible hand-held device, called a dielectric barrier discharge (DBD), is built like a sandwich, Gershman said. "It's a high-voltage slice of bread on cheese that is an insulator and a grounded piece of bread with holes in it," she said.

The high-voltage slice of "bread" is an electrode made of copper tape. The other slice is a grounded electrode patterned with holes to let the plasma flow through. Between these slices lies the "cheese" of insulating tape. "Basically it's all flexible tape like Scotch tape or duct tape," Gershman said. "The ground electrode faces the users and makes the device safe to use."

The room-temperature plasma interacts with air to produce what are called reactive oxygen and nitrogen species -- molecules and atoms of the two elements -- along with a mixture of electrons, currents, and electrical fields. The electrons and fields team up to enable the reactive species to penetrate and destroy bacteria cell walls and kill the cells.

Room-temperature plasmas, which compare with the fusion plasmas PPPL studies that are many times hotter than the core of the sun, are produced by sending short pulses of high-speed electrons through gases like air, creating the plasma and leaving no time for it to heat up. Such plasmas are also far cooler than the thousand-degree plasmas that the laboratory studies to synthesize nanoparticles and conduct other research.

A special feature of the device is its ability to improve the action of hydrogen peroxide, a common antiseptic cleanser. "We demonstrate faster disinfection than plasma or hydrogen peroxide alone in stable low power operation," the authors write. "Hence, plasma activation of a low concentration hydrogen peroxide solution, using a hand-held flexible DBD device results in a dramatic improvement in disinfection."

Novel collaboration

Achieving these results was a novel collaboration that brought together the plasma physics expertise of PPPL and the biological know-how of a laboratory at NJIT. "While we usually are a neurobiology lab that studies locomotion, we were eager to collaborate with PPPL on a project related to COVID-19," said Gal Haspel, a professor of biological sciences at NJIT and a co-author of the paper.

Performing the plasma disinfection tests was co-author Maria Benem Harreguy, a graduate student in biological sciences at NJIT, with assistance from Gershman. "She did all the experiments and without her we wouldn't have this study," Gershman said.

The idea for this research began "as soon as we got into the COVID lockdown last March," said PPPL physicist and co-author Yevgeny Raitses, who directs the Princeton Collaborative Temperature Plasma Research Facility (PCRF) -- a joint venture of PPPL and Princeton University supported by the DOE Office of Science (FES) that provided resources for this work through a user project. "We at PCRF were thinking of how to help in fighting against COVID through our low-temperature plasma research, and it's been exciting for us to continue this collaboration," he said.

Raitses guided the PPPL side of the project, which included setting up the DBD based on a printed surface design and characterizing the plasma discharge in this device, and oversaw the ongoing collaboration with NJIT. Going forward, he said, "we are working to get access to a facility in which we will be able to apply the DBD and other relevant devices against the SARS CoV-2 virus" that causes COVID-19. "Also under way is research with immunologists and virologists at Princeton University and Rutgers University to expand the applicability of developed plasma devices to a broader range of viruses."

Credit: 
DOE/Princeton Plasma Physics Laboratory

Air pollution may affect severity and hospitalization in COVID-19 patients

image: Angelico Mendy, MD, PhD, shown in the University of Cincinnati College of Medicine.

Image: 
Colleen Kelley/University of Cincinnati

Patients who have preexisting respiratory conditions such as asthma or chronic obstructive pulmonary disease (COPD) and live in areas with high levels of air pollution have a greater chance of hospitalization if they contract COVID-19, says a University of Cincinnati researcher.

Angelico Mendy, MD, PhD, assistant professor of environmental and public health sciences, at the UC College of Medicine, looked at the health outcomes and backgrounds of 1,128 COVID-19 patients at UC Health, the UC-affiliated health care system in Greater Cincinnati.

Mendy led a team of researchers in an individual-level study which used a statistical model to evaluate the association between long-term exposure to particulate matter less or equal to 2.5 micrometers — it refers to a mixture of tiny particles and droplets in the air that are two-and-one half microns or less in width — and hospitalizations for COVID-19. Medical records allowed researchers to use patients’ zip codes for estimating their particulate exposure over a 10-year period.

“Particulate matter is very small, small enough to be inhaled deep into the lungs, they cross into the blood and also affect other organ systems,” says Mendy. “Air pollution as a result of emissions from automobiles, factories or other sources is a generator of particulate matter.”

“Our study didn’t find any correlation between severity of COVID-19 and particulate matter in general, but we found something for people who had asthma and COPD,” says Mendy. “People who have preexisting asthma and COPD, when they are exposed to higher levels of particulate matter, they are more likely to have severe COVID-19, severe enough to be hospitalized.”

Researchers found that a one-unit increase in particulate matter 2.5 was associated with a 60% higher chance of hospitalization for COVID-19 patients with pre-existing respiratory disease. For patients without respiratory disease, no association was observed.

The study’s findings were published online in the scholarly journal Respiratory Medicine.

It is the first study to look at an association between air pollution, COVID-19 and individual patients, says Mendy. A study co-author, Xiao Wu, PhD, in the Department of Biostatistics at Harvard University, led a study last year looking at air pollution and COVID-19 mortality in the United States.

“This study may have policy implications such as reducing particulate exposure,” says Mendy. “Many people want to have more clean energy and reduced emissions into the atmosphere.”

Mendy says the findings of his pilot study are preliminary and he hopes to use it to generate support for a larger more comprehensive study of patients. The UC Health patients in the study were diagnosed with COVID-19 between March 13, 2020 and July 5, 2020. The dataset was stripped of all Health Insurance Portability and Accountability Act (HIPAA) identifiers. The median age for patients was 46 and 96.6% were residents of Ohio with the remaining 3.4% coming from Kentucky, Indiana, New York, South Carolina, West Virginia and Iowa.

Other study co-authors from UC include Jason Keller, a researcher in the Department of Bioinformatics; Cecily Fassler, PhD, postdoctoral fellow in the Department of Environmental and Public Health Sciences; Senu Apewokin, MD, an assistant professor in the Department of Internal Medicine; Tesfaye Mersha, an associate professor pediatrics; and Changchun Xie, PhD, and Susan Pinney, PhD, both professors in the Department of Environmental and Public Health Sciences.

Funding for the study included various grants from the National Institutes of Health supporting researchers.

Journal

Respiratory Medicine

Credit: 
University of Cincinnati