Culture

Culling cancer before it stems: A novel, rapid carcinogen detection method

image: Analysis under the microscope of sections of the tumor generated from the cancer stem cells. The staining of Ki-67 shows rapid tumor growth and that of CK and Sox2 indicates poor differentiation. Rapid growth and poor differentiation both re
present malignancy.

Image: 
Juan Du and Masaharu Seno

Today, our lifestyle brings us in contact with multiple chemicals daily: in packaged food, cosmetics, construction materials, aerosols, and so on; a number of these chemicals have been named "carcinogens." A chemical's carcinogenicity is its ability to cause cancer in humans or other living things. Because cancer is a major cause of illness, disability, and death worldwide, scientists have developed several different ways to test chemicals for carcinogenicity in the laboratory. However, these methods are complex and take a long time to yield results, which makes it difficult for scientists to test large numbers of chemicals.

Now, in a paper recently published in Scientific Reports, an international research team led by Professor Masaharu Seno of Okayama University, Japan, reports a new method that can achieve this quickly. "It takes only one week for our method to yield results," notes Prof Seno, and this represents a considerable improvement over existing methods.

The method involves stem cells--precursor cells that mature into various different cells with specialized functions, such as blood cells or neurons. Previously, Prof Seno's research team had used a certain kind of stem cell from mice, called mouse induced pluripotent stem cells, to establish a model in which healthy stem cells converted to "cancerous" stem cells, also called cancer stem cells (or CSCs), in four weeks when kept in a conditioned culture medium of mouse lung cancer cells. In this study, the researchers reasoned that adding a carcinogenic chemical to the conditioned medium should boost this conversion.

Based on this idea, the researchers conducted a series of week-long experiments to test 110 chemicals. At the end of it, they found that three chemicals--namely, PDO325901, CHIR99021, and Dasatinib--had resulted in the formation of CSCs. What's interesting is, all three are actually known to suppress the intracellular signaling that leads to the growth and survival of cancer cells.

When they injected live mice with stem cells that had been exposed to any of those three chemicals, malignant tumors grew in the mice within six weeks. The CSCs obtained by exposing mouse stem cells to the three chemicals also began making more copies of proteins often associated with the growth of cancer cells.

Upon additional analyses, the scientists were able to identify the specific cellular pathways that these chemicals all trigger to cause the conversion.

These findings prove the efficacy and potential of this rapid testing method. Prof Seno speaks of the many applications the method can have: "Because pluripotent stem cells can develop into all cells in an adult human body, a wide range of cancer stem cells can be obtained with our method, enabling the efficient risk assessment of many chemicals for a variety of cancers. This will lead to more precise cancer prevention strategies as well as treatments." He also asserts that this screening method will be "a good resource for studying the mechanisms of cancer development."

Given how many people are afflicted worldwide by cancer every year, methods such as the ones developed in this study and its precursor can make important contributions to the improvement of people's lives.

Credit: 
Okayama University

Drivers from poor cities can be exposed to 80% more air pollution

Car users from the world's least affluent cities are exposed to a disproportionate amount of in-car air pollution because they rely heavily on opening their windows for ventilation, finds a first of its kind study from the University of Surrey.

According to the World Health Organisation (WHO), air pollution kills an estimated seven million people worldwide every year and nine out of 10 people breathe air with high levels of pollutants.

In a study published by the Science of the Total Environment journal, a global team of researchers led by Surrey's Global Centre for Clean Air Research (GCARE) investigated air pollution exposure levels for commuters in 10 different global cities - Dhaka (Bangladesh), Chennai (India), Guangzhou (China), Medelli?n (Colombia), Sa?o Paulo (Brazil), Cairo (Egypt), Sulaymaniyah (Iraq), Addis Ababa (Ethiopia), Blantyre (Malawi), and Dar-es-Salaam (Tanzania).

The research team investigated PM2.5 and PM10 exposure levels inside vehicles during peak hours in the morning and evening, as well as off-peak hours in the middle of the day. The scientists measured how exposure levels changed when drivers used recirculation systems, fans and simply opened the windows.

The study discovered that drivers in some of the world's poorest cities experienced higher levels of in-car pollution.

Irrespective of the city and car model used, a windows-open setting showed the highest exposure, followed by fan-on and recirculation. Pollution exposure for windows-open during off-peak hours was 91 percent and 40 percent less than morning and evening peak hours, respectively. The study also found that the windows-open setting exposed car passengers to hotspots of air pollution for up to a third of the total travel length.

The study found that commuters who turn on the recirculation are exposed to around 80 percent less harmful particles than those who open their car windows. Car cabin filters were more effective in removing pollution than fine particles, suggesting that if new cars had more efficient filters, it could reduce the overall exposure of car commuters.

Professor Prashant Kumar, Director of GCARE at the University of Surrey, said: "To be blunt, we need as many cars as possible off the road, or more green vehicles to reduce air pollution exposure. This is yet a distant dream in many ODA countries. Air-conditioned cars are unattainable for many poor and vulnerable commuters across the world, but our data is clear and coherent for all 10 participating cities.

"We must now work with our global partners to make sure they have the information needed to put in place programmes, policies and strategies to protect the most vulnerable in our communities and find realistic solutions to these serious problems."

Professor Abdus Salam from the University of Dhaka said: "The study has drawn important conclusions that can help commuters make decisions in their day-to-day lives to protect their health. Simple choices, like travelling during off-peak hours, can go a long way in reducing their exposure to air pollution."

Professor Adamson S. Muula from the University of Malawi said: "Working with the GCARE team and global collaborators on this study has been an insightful experience. We were given access to affordable technology to collect novel datasets that haven't been available for cities in this part of the world. We also got to see where our cities stand in comparison to other global cities in developing countries. This has allowed for the sharing of much needed knowledge and best practices."

Credit: 
University of Surrey

TLK protein inhibition activates the innate immune system

image: TLK inhibition show replication intermediates (green) at chromosome ends (red)

Image: 
(IRB Barcelona)

Tousled-like kinases (TLKs) are a potential therapeutic target for cancer treatment due to their central role in DNA repair and replication. The latest work by IRB Barcelona's Genomic Instability and Cancer Laboratory, led by Travis H. Stracker, concludes that TLK inhibition activates the innate immune system, a very important factor in the response to cancer.

"We believe the TLKs are promising targets for cancer therapy and want to understand more about how they work and how cells respond to their reduction or loss," says Stracker. Having headed the Genomic Instability and Cancer Laboratory at IRB Barcelona since 2009, in July this year Stracker took up a new position as group leader at the National Cancer Institute (NIH) in Bethesda, in the US.

Alternative lengthening of telomeres

The group of researchers had previously observed that reduced TLK activity made cancer cells more sensitive to some therapeutic agents. Now, they have found that blocking TLKs triggers an alternative telomere lengthening system (ALT), a pathway used by many cancers, including some of the most aggressive ones like glioblastoma, to maintain telomeres and allow cells to continue dividing.

The group of researchers has discovered that activation of the ALT pathway triggers the innate immune system, potentially attracting immune cells, such as macrophages and T lymphocytes. "The activation of innate immunity in cancer has recently become an active area of research as it has become clear that the innate immune response influences chemotherapy and immunotherapy," comments Stracker.

Genome decondensation and accessibility

In DNA, not all regions have the same function. Some regions contain genes with the information necessary to make proteins, but there are other regions, called heterochromatin, that have a regulatory and structural function, but do not contain genes that give rise to proteins. Another effect of TLK inhibition, observed in this study, is that this heterochromatin, which is usually compacted, ceases to be so, thereby becoming more accessible to the RNA production machinery and leading to an altered composition in the cell.

"This could help us understand our previous observation that TLK depletion caused replication stress and help us exploit the effects of TLK depletion for cancer therapy," says Sandra Segura-Bayona, first author of the study. Segura Bayona is currently a postdoctoral fellow in the laboratory headed by Simon Boulton at The Francis Crick Institute in London.

Credit: 
Institute for Research in Biomedicine (IRB Barcelona)

The role of Chinese cultural values in illegal wildlife trade interventions

A new study by the University of Kent's Durrell Institute of Conservation and Ecology (DICE) suggests that utilising Confucianist, Daoist, and Buddhist belief messaging in targeted campaigns could effectively change the behaviour of end consumers in the East Asia illegal wildlife trade chain.

Behavioural change intervention is essential for reducing the demand of illegal wildlife products. With so many conservation campaigns typically approached from the perspective of Western culture, the impact could be limited in different cultures. East Asia is a primary market for many illegal wildlife products such as rosewood, ivory, and pangolin scales and so is often targeted with conservation campaigns, but with limited effect.

The research led by Laura Thomas-Walters, a PhD student studying Conservation Biology at DICE, has identified that resonating with Chinese-influenced societies through cultural values could be most effective for tailoring the messaging in illegal wildlife trade campaigns in East Asia. While China alone has 56 recognised ethnic groups, Confucianism, Daoism, and Buddhism have dominated traditional Chinese ideology.

The study highlighted eight cultural concepts to target messaging around; Harmony (the balance of yin and yang), Jian (frugality), Junzi (an exemplary person), Li (ritual propriety), Qi (the material force of the universe), Ren (inner moral force, humaneness), Shu (altruism) and Zhong (conscientiousness).

For example, in regards to the concept of harmony, messaging could be based around unsustainable product use and the imbalance between humans and nature when species such as pangolins disappear from nature. While in regards to Ren, messaging could reinforce the concept of connection and unity with nature by relating the kindness of humanity to include wildlife.

Laura Thomas-Walters said: 'Chinese culture has a long history of consumptive wildlife use and conservationists have struggled to engage Chinese-influenced societies with illegal wildlife trade campaigns. This study suggests routes that could be taken to target these societies more specifically. Yet, it's important to consider that when designing an intervention, respect rather than judgement is essential, and the involvement of a local partnership or regional expertise is recommended.'

Credit: 
University of Kent

How tumor cells evade the immune defense

image: (from left) Dr. Maike Effern, Dr. Nicole Glodde and Prof. Dr. Michael Hölzel.

Image: 
© Barbara Frommann/Uni Bonn

Scientists are increasingly trying to use the body's own immune system to fight cancer. A new study by the University of Bonn and research institutions in Australia and Switzerland now shows the strategies tumor cells use to evade this attack. The method developed for this work contributes to a better understanding of the "arms race" between immune defense and disease. The results could help to improve modern therapeutic approaches. They have been published in the journal Immunity.

Cancer cells differ from healthy body cells - in their appearance, their behavior and the genes that are active in them. Often this does not go unnoticed: The immune system registers that something is wrong and dispatches its troops to fight the tumor. However, this response is often too weak to keep the cancer in check in the long term or even destroy it.

Researchers have therefore been trying for many years to strengthen the immune system's defensive reaction. They do this in a similar way to a policeman who puts his dog on the trail of an escaped criminal. In this case, the role of the sniffer dog is taken over by the cytotoxic T cells: They can detect and kill sick or defective cells. Each T cell is directed against a specific characteristic, also called antigen. For cancer therapy, the researchers are therefore looking for T cells in patients that detect tumor antigens. They can then for instance multiply these and inject them back into the patient. In this way they strengthen the patient's immune response against the cancer.

However, many tumors have unfortunately developed strategies that enable them to evade the immune system. "In our study, we investigated what these strategies look like and what this depends on," explains Dr. Maike Effern from the Institute of Experimental Oncology at the University Hospital Bonn. "We focused on skin cancer, namely melanoma cells."

Melanomas differ from healthy cells in several ways. For example, a whole range of different genes are active in them. Each of these is a potential antigen for T cells. But which is particularly suitable for triggering a strong and lasting immune response? To answer this question, the researchers invented a clever method in their experimental model: They attached a kind of label to various genes that are active in the development of melanoma cells and used them to produce antigens. They then released a group of T cells against the tumor cells, which recognized exactly this molecular label as a disease marker. The researchers then used this strategy to investigate how the cancer cells react to being pursued by the immune system. Depending on the gene tagged with such a label, they found significant differences.

Cancer cells hide from the immune system

"When the T cells were directed against genes responsible for melanoma-typical characteristics, we observed that the cancer cells changed their appearance and suppressed these genes over time," explains Effern's colleague Dr. Nicole Glodde. "So this is how they hide from the immune system."

In contrast, another gene investigated in the study is essential for the tumor's survival. This makes it not so easy to downregulate and thus hide. "In our view, this gene therefore has the potential to induce a very effective T cell response," Effern emphasizes. "Our work potentially clears the way to more effective immune therapies," hopes Prof. Dr. Michael Hölzel, head of the Institute of Experimental Oncology at the University Hospital Bonn and member of the Cluster of Excellence ImmunoSensation at the University of Bonn. "The method we have developed also makes it possible to better understand the processes by which cancer cells slip under the radar of the immune system."

Credit: 
University of Bonn

Scientists discover the switch that makes human brown fat burn energy

An international research team have discovered how to activate brown fat in humans, which may lead to new treatments for type 2 diabetes and obesity. The results of the collaboration between the Centre de recherche du Centre hospitalier universitaire de Sherbrooke (CRCHUS) and the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen were published today in Cell Metabolism.

Brown fat burns energy and generates heat - a process called thermogenesis - after being activated by cold temperature or chemical signals. Humans have small deposits of brown fat, and scientists have long hypothesized that finding alternative ways to pharmacologically activate the fat could help improve metabolism.

Scientists have now discovered that beta2-adrenergic receptors (b2-AR) in brown fat cells are responsible for stimulating thermogenesis. According to Dr. Denis Blondin from CRCHUS, the finding could explain why most clinical trials, which have attempted to induce BAT to burn energy, have performed poorly.

"We show that perhaps we were aiming for the wrong target all along. In contrast to rodents, human BAT is activated through the stimulation of the beta2-adrenergic receptor, the same receptor responsible for the release of fat from our white adipose tissue."

Unlocking the therapeutic potential of brown fat

According to Associate Professor Camilla Schéele at CBMR, this finding has clear therapeutic applications.
"Activation of brown fat burns calories, improves insulin sensitivity and even affects appetite regulation. Our data reveals a previously unknown key to unlocking these functions in humans, which would potentially be of great gain for people living with obesity or type 2 diabetes".

A second phase of research will begin in the autumn, which will attempt to validate the finding by activating brown fat with drugs that target b2-AR, explains Professor André Carpentier from CRCHUS:

"Our next step will be to use a drug that specifically activate that target on brown fat and determine how much it could be of use to burn fat and calories in humans. Once this is done, studies in patients with type 2 diabetes will start to determine if this approach can be useful to improve the metabolic control of the disease."

Credit: 
University of Copenhagen - The Faculty of Health and Medical Sciences

Herbicide harming marsupial health and development, research finds

image: The research found that concentrations of atrazine have been recorded at disturbingly high levels in Victorian rivers and Tasmanian streams immediately after forestry spraying.

Image: 
Pexels Ethan Brooke

The health of wallabies and kangaroos is being affected by the herbicide, atrazine, which is used widely in Australia on cereal crops and in forestation to prevent weeds, according to new research.

Atrazine, which has been banned in the European Union since 2003, may be impacting reproduction in marsupials, the University of Melbourne study found, published today in Reproduction, Fertility and Development.

"Exposures to atrazine is causing major abnormalities in the male reproductive system in many animals, triggering male sterility or even male-to-female sex reversal in frogs," Professor in Genetics Andrew Pask said.

"With the marsupial's unique mode of reproduction and the young completing their development in the pouch, mothers are unknowingly passing the toxins on in their breast milk, exposing their young to environmental toxins."

The study is the first time the impacts of pesticides have been investigated in any marsupial and show that they are able to affect reproductive development.

The research found that concentrations of atrazine have been recorded at disturbingly high levels in Victorian rivers and Tasmanian streams immediately after forestry spraying.

Kangaroos and wallabies are at high risk because they eat the sprayed crops and drink from contaminated water resources where chemicals such as atrazine accumulate from run off.

Atrazine affects a broad range of animals from mammals such as rats to amphibians, reptiles and even fish.

With marsupials already experiencing devastating population declines across Australia, and 21 per cent of native mammals currently threatened with extinction, researchers say the potential impacts of environmental toxins are of major concern.

Researchers exposed the adult female tammar wallabies to atrazine contaminated water throughout pregnancy, birth and lactation to help establish the extent of harm being caused by the chemical.

They then examined the reproductive development of their young by assessing their growth and development.

Lead author on the research and PhD student Laura Cook said it is hoped the study will lead to more stringent guidelines around the use of atrazine in Australia.

"Endocrine-disrupting chemicals, such as atrazine, have the ability to impact development and increase disease susceptibility," she said.

"With increased habitat destruction, marsupials are being pushed onto farmland, attracted to the food resources and rare permanent water sources where they may be vulnerable to agricultural contaminants, such as pesticides."

Credit: 
University of Melbourne

COVID-19 a perfect storm for conspiracy theories

image: COVID-19 a perfect storm for conspiracy theories - QUT research tracks Facebook rumours of 5G causing the pandemic.

Image: 
QUT Marketing and Communication

As the global count of COVID-19 infections heads towards the 20M mark, the pandemic has created what the World Health Organisation calls an 'infodemic', giving conspiracy groups a bigger platform than ever before.

Researchers from QUT's Digital Media Research Centre have taken a deep dive into their world to trace wild rumours on Facebook claiming the coronavirus was caused by 5G technology. They found what was once being preached to the already converted was quickly fanned further afield by social media and celebrities spreading the message.

Professor Axel Bruns, Associate Professor Stephen Harrington and Dr Edward Hurcombe have published their first major output from their Australian Research Council Discovery project Evaluating the Challenge of 'Fake News' and Other Malinformation.

Working with researchers from Monash University (Melbourne), Syracuse University (USA), and Cardiff University (UK), the project runs from mid-2020 to mid-2023. The first major article - 'Corona? 5G? Or Both?: The Dynamics of COVID-19/5G Conspiracy Theories on Facebook' has just been published in in Media International Australia.

It traces in detail the developments around the nonsensical and dangerous belief that 5G technology could cause or exacerbate the symptoms of a severe viral infection.

"Pre-existing conspiracy groups have jumped on the COVID-19 bandwagon and retrofitted their conspiracy theories to the pandemic, to argue the coronavirus outbreak justifies and proves their claims," said Professor Bruns.

"If you are against the roll-out of 5G, for example, then you link it with COVID-19. Other COVID-19 related conspiracy theories include claims it was developed in laboratory in Wuhan, or that it is a ruse by a secret 'world government' to suppress civil liberties."

Dr Hurcombe said that the research focussed on the COVID-5G rumour because of all the COVID-related misinformation stories, it has generated the most immediate and visible impacts. In April, mobile phone towers in the UK, The Netherlands and elsewhere were attacked.

"Much of the early circulation of COVID/5G mis- and disinformation remained niche and reached only existing conspiracy communities. It also existed early on in a wide range of languages, but English-language content contributed most prominently to its spread," said Dr Hurcombe.

"We found lockdowns and other government restrictions seemed to lead to a growth in COVID/5G misinformation; this may be due to people assuming some kind of hidden agenda behind them, but also simply a sign of people having more time on their hands to search social media for coronavirus-related content."

Professor Harrington added that celebrities like singer Keri Hilson and actor Woody Harrelson played a significant role in amplifying mis- and disinformation beyond established conspiracist communities.

"Musicians, actors, sportspeople, and fringe politicians, but (especially in Africa) also evangelist preachers, have all been guilty of this," said Professor Harrington.

"Coverage of their statements in entertainment and mainstream media further amplified such misinformation, even if the media coverage was critical."

Professor Bruns said when governments and health spokespeople were forced to respond to conspiracy theories, and mainstream media publish factchecks, the conspiracy theorists have reached their aims.

"It's win-win for the conspiracy theorists - when their claims are widely reported, even critically, they can then present any denials of their claims as evidence that the government is trying to suppress 'the truth'," he said.

"This makes the true believers even more committed.

"However, debunking is still valuable if it stops other citizens from falling prey to such mis- and disinformation. The same is true for content warnings and takedowns: conspiracy theorists will see them as proof that there really is a conspiracy, but at least they stop the content from circulating any further."

Read the full article at: https://journals.sagepub.com/doi/10.1177/1329878X20946113

Media contact:
Amanda Weaver, QUT Media, 07 3138 3151, amanda.weaver@qut.edu.au
After hours: Rose Trapnell, 0407 585 901, media@qut.edu.au

Credit: 
Queensland University of Technology

Absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication

In a new study in Cell Discovery, Chen-Yu Zhang's group at Nanjing University and two other groups from Wuhan Institute of Virology and the Second Hospital of Nanjing present a novel finding that absorbed miRNA MIR2911 in honeysuckle decoction (HD) can directly target SARS-CoV-2 genes and inhibit viral replication. Drinking of HD accelerate the negative conversion of COVID-19 patients.

The search for clinically effective therapy for Covid-19 has not been successful to date. Many broad spectrum anti-viral agents have failed the test. In previous studies, Zhang's group has demonstrated that a plant microRNA, MIR2911, which is enriched in HD, could directly target influenza A viruses (IAV) including H1N1, H5N1 and H7N9. Drinking of HD can prevent IAV infection and reduce H5N1-induced mice death. They have also revealed that absorbed exogenous miRNAs (including MIR2911 in HD) can be packaged into exosomes, released to circulation, and then delivered into recipient cells as functional secreted miRNAs.

In the current study, they report that MIR2911 in HD can also suppress SARS-CoV-2 infection. The SARS-CoV-2 genome has up to 28 binding sites of MIR2911 which were confirmed by the classic luciferase assay. Cellular-exosomal-MIR2911 at 13.2 pM concentration (cellular exosomes were collected from culture medium of HEK293T cells transfected with synthetic MIR2911 or control ncRNA) inhibited 93% virus replication, indicating that exosomal MIR2911 directly and sufficiently inhibits SARS-CoV-2 replication.

The MIR2911 concentration in HD was about 52.5 pM (10.5 pmol/200 ml/30 g dried honeysuckle). Serum levels of MIR2911 in heathy volunteers two hours after drinking 200 ml HD were about 0.67 pM. The antiviral function of exosomes with/without MIR2911 collected from the same donor before and after drinking HD were assessed. Exosomes containing MIR2911 (MIR2911 levels: nondetectable before drinking; 57.9 fM after drinking) significantly inhibited virus replication.

A clinical study further confirmed the anti-viral effect of MIR2911 from HD. Patients who already received routine antiviral therapy were divided into two groups, one group received additionally MIR2911 in HD (10.5 pmol/200 ml/30 g dried honeysuckle/day, MIR2911+), the other group receive normal traditional Chinese medicine (TCM) mixture (sequenced to be free of MIR2911-). The time taken to become SARS-CoV-2 PCR-negative (TTN) significantly favored patients treated with HD-MIR2911 (median 4.0 vs 12.0 days, HR 0.11, 95% CI 0.025-0.46, P=0.0028), indicating that MIR2911 in HD accelerates the negative conversion of infected patients.

1) This study demonstrated that absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication and accelerates the negative conversion of infected patients.

2) It provides a practicable and reliable therapeutic strategy to treat SARS-CoV-2 infection.

3) This is the first time that exosomes with/without MIR2911 collected from the same donor before and after drinking HD were used to assess absorbed dietary miRNA function, further supporting that absorbed dietary miRNA plays the important role of cross-kingdom regulation in human consumer.

4) The data that MIR2911 (~60 fM) in exosomes significantly inhibits virus replication not only confirms the extra-high antiviral activity of MIR2911 (compared to that of remdesivir: 3.7 μM and Chloroquine: 10 μM) but also provides a novel and the most similar condition in vivo to assess the efficacy of potential drugs in vitro.

"We wished we could provide really useful information to help stop the pandemic in the darkest hour". Chen-Yu Zhang said. "The focus of this study is to demonstrate that absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication sufficiently. On the other hand, in the study titled "Decreased HD-MIR2911 absorption in human subjects with the SIDT1 polymorphism fails to inhibit SARS-CoV-2 replication", we have shown that synthetic MIR2911, cellular-exosomal MIR2911 and serum-exosomal MIR2911 directly inhibited SARS-CoV-2 S-protein expression and SARS-CoV-2 replication. More importantly, decreased HD-MIR2911 absorption resulted in non-inhibitory effect on replication, indicating that MIR2911in HD is necessary to suppress SARS-CoV-2. Therefore, we propose medical doctors and scientists from all over the world to carry out HD-MIR2911 clinic trails in order to help treating SARS-CoV-2 infection." Zhang added.

Credit: 
Nanjing University School of Life Sciences

Study sheds new light on vein formation in plants

An international team of researchers including the University of Adelaide, has found plant hormones known as strigolactones suppress the transportation of auxin, the main plant hormone involved in vein formation, so that vein formation occurs slower and with greater focus.

The research, published in Nature Communications, brings new knowledge about how hormones regulate plant growth, knowledge that will ultimately contribute to scientists' quest to improve crop productivity.

Co-author, Dr Philip Brewer of the University of Adelaide's Waite Research Institute, said scientists know that the interaction between strigolactones and auxin is important for plant responses, but further research in this area is essential to learn how.

Vascular plants have veins in leaves, stems and roots that carry water and nutrients to cells, and provide structural support. The hormone auxin flows from new leaves and buds to connect them together and joins them with the stem, and re-joins veins at wound sites, a process call canalisation.

"Although only recently identified, what we know about strigolactone hormones is that they help plants respond to environmental conditions, such as optimising plant growth to match soil nutrient levels," said Dr Brewer.

"By observing the interaction of the two hormones in pea and thale cress plants in this study, we found that when applied, strigolactones reduce the transport of auxin and slow vein formation.

"Strigolactones also supress auxin as it flows through root tips. Specifically, strigolactones limit the way auxin promotes its own transport out of cells," said Dr Brewer.

Dr Brewer said plant hormones like auxin and strigolactones have great potential to improve crop productivity.

"However, understanding how they act is still a major research challenge, and applying hormones in agriculture often results in unwanted side effects," said Dr Brewer.

"Improved knowledge of how the hormones act allows us to uncover ways to fine-tune hormone responses so that we can realise the benefits and limit the side effects.

"While more research is needed in this field, this study contributes to fundamental knowledge of plant biology and offers hope of finding new ways to adapt crops to increasingly difficult climate conditions," Dr Brewer said.

Credit: 
University of Adelaide

Projecting early molecular signatures of AD through the convergence study of Omics and AI

image: Overview of the application of the GANs to bulk RNA-seq data.

Image: 
@ Korea Brain Research Institute

Korea Brain Research Institute (headed by Suh Pann-ghill) announced on July 24 the discovery that an increase in amyloid-beta in the brain alters cholesterol biosynthesis, which was found by Dr. Cheon Mookyung of KBRI through RNA-seq analysis data (omics) using AI.

* Omics: "Omics" combines the prefix omni-, meaning "all", and the suffix -ics, meaning "study". Omics refers to the study of important information related to vital phenomena such as the activities of proteins that make up the genetic materials of the human body.

The research results were published in PLOS Computational Biology, an international academic journal in the field of computational biology, and the title and authors of the paper are as follows.

*Title: A practical application of generative adversarial networks for RNA-seq analysis to predict the molecular process of Alzheimer's disease

*Author: Jinhee Park(1st Author), Hyerin Kim, Jaekwang Kim, Mookyung Cheon(Corresponding Author)

Amyloid-beta is known as a protein that causes Alzheimer's disease (AD). In a normal brain, if it accumulates excessively, it is removed by microglia*, etc. Cholesterol must also be kept at a certain level within the blood to compose the cell membrane, adjust fluidity in the membrane, and maintain homeostasis. If the abovementioned processes are not carried out properly, pathological abnormalities occur in the body.

* Microglia: A type of neuroglia located throughout the brain and responsible for active immune defense

The research team analyzed the cerebral cortex tissue data of AD mouse models using the cutting-edge deep learning technique of generative adversarial networks (GANs)*. A GAN is an algorithm that generates data through competition between a generator and discriminator, studies the generated data, and creates synthetic data close to real images. The GANs technique was used to create the fake speech video of President Barack Obama and can be applied to continuous face aging.

The research team performed an AD genetic expression simulation in mice using GANs and observed the changing process of gene expression from normal to AD state. As a result, it was discovered that Amyloid-beta increases and alters cholesterol biosynthesis in the early stages of the disease. This discovery was also confirmed by the RNA-seq analysis of postmortem brain tissue.

This means that the increase in Amyloid-beta triggers cholesterol biosynthesis and that the two processes in combination are likely to engage in synaptogenesis and synaptic plasticity by interacting with each other.

This study is based on the unique research technique of the convergence of bioinformatics and AI, and its significance lies in that it provides designs for more systematic interpretation and experimentation to researchers and proposes a new approach for projecting biological changes in the early stages of disease progression to the healthcare industry.

Dr. Cheon said, "GANs are a useful tool for analyzing the disease-induced differences in gene expression and for explaining the molecular progress by identifying the cause of the phenomenon. The continued expansion of this methodology and omics data accumulation are expected to help us overcome the largest limitation in analysis related to brain diseases and aging, which is the time-consuming process of acquiring samples."

This study was supported as an exclusive project by KBRI.

Credit: 
Korea Brain Research Institute

Grooming behavior between dairy cows reveals complex social network

image: The experimental herd.

Image: 
Gustavo E. Monti

Like humans, cattle are social creatures with complex relationships that change as group dynamics evolve. A study published in Frontiers in Veterinary Science offered new insights into the social networking behavior of dairy cows, building on a body of research that could someday help reshape farm management practices to create healthier living environments for the animals.

A team of Chilean and US scientists spent 30 days observing a small herd of dairy cows that had recently given birth to understand the web of bovine interactions based on social grooming behavior, also known as allogrooming.

In modern dairy production systems, cows are constantly shuffled into different groups depending on factors such as lactation stage, nutrition requirements and breeding. The animals must re-establish their social structure during each regrouping, which previous research has shown causes negative effects on behavior, health and productivity.

Allogrooming, which generally involves one cow licking another around the head and neck, is believed to serve a number of social purposes. For instance, social grooming is both a way to establish individual bonds between members of a group and also enhances overall social cohesion in the herd.

"Our aim was to understand how social networks are formed by cows after they are reunited at the beginning of the milking period, and what factors may influence these changes. This is important because cattle form strong bonds, which offer them social support and help them cope with the stressors that occur regularly in dairy cows' lives," says lead author Dr Gustavo E. Monti from the Institute of Veterinary Preventive Medicine at the Austral University of Chile.

The study took place at a pasture-based dairy farm at an agricultural research station in the south-central city of Valdivia. Researchers recorded a total of 1,329 allogrooming events from 38 cows during the month-long experiment.

Their observations uncovered a variety of patterns based on different attributes, such as each animal's age and social rank. For example, cows tended to groom individuals that had previously groomed them, implying mutual cooperation. They also tended to prefer individuals of similar age, suggesting a certain familiarity because they grew up together.

Meanwhile, the most active groomers that did not seem to prefer specific individuals actually received less attention from other group members over time. And older individuals groomed more cows than younger ones, suggesting that allogrooming could be related to seniority.

"Our results indicate that licking behavior is important to make friends and to maintain harmony in the herd. That older cows groom more individuals suggests that they take the role of "peacemakers" in the herd," says Monti.

The observational study used a modern sociological research method called social network analysis, which reconstructs social interactions graphically using nodes that represent individuals and links that refer to relationships that connect them. While such analyses have been used to understand animals social networks, this research is one of the first to employ a statistical modeling method known as stochastic actor-oriented modeling (SAOM) to mammals other than humans. The SAOM framework crunches data on individual attributes and group dynamics to understand how group members change their relationships over time.

"It is important for farmers to be mindful of the relevance of the social aspects of the lives of cows, animals that form complex emotional relationships within their group. Farmers should be aware that cows frequently grooming each other is a positive sign that means that those cows get along. On the contrary, if social grooming declines, it may be a sign of impaired welfare. This new knowledge should be translated into innovative practical strategies that will result in the continued integration of cattle emotional and social needs into management systems," says Monti.

Credit: 
Frontiers

How animation speed affects consumers' perception of product size

Researchers from University of Hong Kong, Yonsei University, and Chinese University of Hong Kong published a new paper in the Journal of Marketing that examines the relationship between animated movement speed in video ads and consumers' assessment of the product size.

The study forthcoming in the Journal of Marketing is titled "Speed Up, Size Down: How Animated Movement Speed in Product Videos Influences Size Assessment and Product Evaluation" and is authored by Michael Jia, B. Kyu Kim, and Lin Ge.

In video ads, products cannot be shown at their actual physical sizes. When no explicit size information or point of reference is provided, product size may be unclear to consumers. Given the potential ambiguity and the importance of size assessment in consumer preference formation, it is highly beneficial for marketers to know what visual cues consumers might use to infer the physical size of a product shown in video ads.

Video advertising often involves dynamic presentations of products that are displayed to move in a lively fashion, similar to how animals move. For instance, an audio speaker can be animated to flash in, bounce, turn around, or spin actively in video ads although it cannot move spontaneously in reality. In this case, the overall animated movement pattern may look similar to various movements insects or birds perform in the air, fishes perform in the water, dancers perform on the stage, or superheroes perform in movies. As another example, when a Swiss Army knife is animated to unfold its moveable parts (e.g., blade and corkscrew) or transform its shape, these movements may also to some extent resemble the way animals move their body parts. When creating video ads, graphic designers can animate products to move either faster or slower.

Jia explains that, "We conducted a series of experiments to examine whether and how the animated movement speed of a product displayed in video ads can influence consumers' size assessment of the product. We found a speed-based scaling effect, meaning that consumers estimate the size of a product to be smaller when the product is animated to move faster in video ads." Moreover, a product's animated movement speed is more likely to color product size assessment for consumers who perceive the product's animated movement pattern as more similar to animals' movement patterns.

The findings offer important implications for marketers, graphic designers, and online advertisers. For products for which a small size is preferred by consumers due to considerations of portability or storage constraint (e.g., mobile devices), practitioners can animate products' movements to be fast in video ads to communicate a small product size. In contrast, for edible products (e.g., food and drinks) and household products (e.g., detergents), consumers generally consider large product size desirable. To summarize the practical value of the research, Kim says, "Practitioners should avoid fast animated movements for these products in video ads if they adopt a value-based positioning such as a larger quantity for the same price. To leverage the speed-based scaling effect, practitioners can animate a product to move like animals' movement patterns."

In the contemporary digital era, consumers are constantly exposed to product videos. When creating video ads, practitioners should be aware of the general negative relationship between animated movement speed and size assessment. Guided by this principle, they can determine the ideal animated movement speeds for their products through speed calibration tests tailored to their products' natures and marketing communication objectives.

Credit: 
American Marketing Association

A targeted treatment for emphysema?

image: When researchers at Boston Children's Hospital tested PR1P in lung cells and mouse models of emphysema, they found that it protected VEGF from being degraded, prevented cell death, and protected the lung.

Image: 
Hao Wu, PhD, Boston Children's Hospital

Emphysema is a progressive, debilitating lung disease in which the lung's breathing sacs, or alveoli, enlarge, get thinner, and eventually are destroyed as the cells die off. It can be fatal, and there is currently no cure. New research at Boston Children's Hospital, using lung cells and mouse models of emphysema, offers hope in the form of a small, engineered peptide molecule called PR1P. Findings were published July 14 in the American Journal of Respiratory Cell and Molecular Biology.

The peptide was developed by Avner Adini, PhD, Robert D'Amato, MD, PhD, Benjamin Matthews, MD, and other colleagues in Boston Children's Vascular Biology Program, based on previous research. That research had found that vascular endothelial growth factor (VEGF), known to be key for blood vessel development, also helps to keep lung tissue healthy, and that VEGF signaling goes awry in emphysema, hastening cell death.

"VEGF is found at high levels in the normal lung -- more than 500 times the levels seen in blood plasma," says Adini. "VEGF levels tend to become dramatically disrupted during lung disease, but return to normal during recovery. It is not clear whether VEGF dysregulation is the root cause of lung disease, or the result of the lung pathology. In emphysema, VEGF activity is low."

Maintaining VEGF levels in the lung

The scientists' first thought was to try to give VEGF directly as a therapy, but VEGF has a very short half-life and can potentially produce serious side effects, including low blood pressure, in animal models.

"So we asked, could there be an alternative way to upregulate VEGF signaling to make it more potent, rather than directly boost VEGF concentrations in the lung?" says Adini.

Serendipitously, through previous research on melanoma, Adini discovered a protein called prominin-1 bound directly to VEGF. Using molecular biology and genetic engineering approaches, he and his colleagues fashioned PR1P, a small peptide comprised of the same 12 amino acids that prominin-1 uses to bind to VEGF.

Protecting the lungs in emphysema models

When the team tested PR1P in lung cells and mouse models of emphysema, they found that it protected VEGF from being degraded. In fact, mice that inhaled PR1P had significantly increased VEGF levels in their lungs as early as 30 minutes after treatment. VEGF levels remained twice as high as in control animals 24 hours later.

Importantly, the researchers further found that PR1P reduced apoptosis (programmed cell death, a key feature in emphysema) in both cell cultures and in live mice. Finally, they showed that PR1P reduced lung damage in mice with toxin-induced emphysema that were followed for 4 and 21 days. Although the study was not designed to assess toxicity, they did not observe any adverse effects.

In addition to emphysema, PR1P may have therapeutic potential for acute respiratory distress syndrome (ARDS), a common and devastating disease which also has no cure and is also characterized by abnormalities in VEGF signaling. Adini and Matthews have funding from the Boston Biomedical Innovation Center (B-BIC) to support their ongoing work to develop PR1P as a therapeutic for both emphysema and ARDS.

"We are now also seeing dramatic lung-preserving and anti-inflammatory effects of inhaled PR1P in mice exposed to multiple diverse toxins that induce lung injury in ARDS models," says Adini.

Credit: 
Boston Children's Hospital

Surface clean-up technology won't solve ocean plastic problem

image: Plastic bag in the ocean

Image: 
Making Oceans Plastic Free

Clean-up devices that collect waste from the ocean surface won't solve the plastic pollution problem, a new study shows.

Researchers compared estimates of current and future plastic waste with the ability of floating clean-up devices to collect it - and found the impact of such devices was "very modest".
However, river barriers could be more effective and - though they have no impact on plastic already in the oceans - they could reduce pollution "significantly" if used in tandem with surface clean-up technology.

The study - by the University of Exeter, the Leibniz Centre for Tropical Marine Research, the Leibniz Institute for Zoo and Wildlife Research, Jacobs University and Making Oceans Plastic Free - focusses on floating plastic, as sunk waste is difficult or impossible to remove depending on size and location.

The authors estimate that the amount of plastic reaching the ocean will peak in 2029, and surface plastic will hit more than 860,000 metric tonnes - more than double the current estimated 399,000 - by 2052 (when previous research suggested the rate of plastic pollution may finally reach zero).

"The important message of this paper is that we can't keep polluting the oceans and hoping that technology will tidy up the mess," said Dr Jesse F. Abrams, of the Global Systems Institute and the Institute for Data Science and Artificial Intelligence, both at the University of Exeter.

"Even if we could collect all the plastic in the oceans - which we can't - it's really difficult to recycle, especially if plastic fragments have floated for a long time and been degraded or bio-fouled.

"The other major solutions are to bury or burn it - but burying could contaminate the ground and burning leads to extra CO2 emissions to the atmosphere."

Private initiatives proposing to collect plastic from oceans and rivers have gained widespread attention recently.

One such scheme, called the Ocean Cleanup, aims to clean the "Pacific garbage patch" in the next 20 years using 600m floating barriers to collect plastic for recycling or incineration on land.

The new study analysed the impact of deploying 200 such devices, running without downtime for 130 years - from 2020 to 2150.

In this scenario, global floating plastic debris would be reduced by 44,900 metric tonnes - just over 5% of the estimated global total by the end of that period.

"The projected impact of both single and multiple clean up devices is very modest compared to the amount of plastic that is constantly entering the ocean," said Dr Sönke Hohn, of Leibniz Centre for Tropical Marine Research.

"These devices are also relatively expensive to make and maintain per unit of plastic removed."

As most plastic enters the oceans via rivers, the authors say a "complete halt" of such pollution entering the ocean using river barriers - especially in key polluting rivers - could prevent most of the pollution they otherwise predict over the next three decades.

However, due to the importance of large rivers for global shipping, such barriers are unlikely to be installed on a large scale.

Given the difficulty of recycling and the negative impacts of burying or burning plastic, the study says reducing disposal and increasing recycling rates are essential to tackle ocean pollution.
"Plastic is an extremely versatile material with a wide range of consumer and industrial applications, but we need to look for more sustainable alternatives and rethink the way we produce, consume and dispose of plastic," said Professor Agostino Merico, of Leibniz Centre for Tropical Marine Research and Jacobs University.

Dr Roger Spranz, an author of the study, is a co-founder of non-profit organisation Making Oceans Plastic Free.

"We have developed expertise in changing behaviour to break plastic habits and stop plastic pollution at its source," Dr Spranz said.

"We are registered in Germany but the focus of our activities and collaborations is in Indonesia, the second-largest source of marine plastic pollution.

"Working with local partners, the implementation of our Tasini campaign in Indonesia has to date helped to prevent an estimated 20 million plastic bags and 50,000 plastic bottles from ending up in coastal areas and the ocean."

Credit: 
University of Exeter