Tech

A research group led by Prof. PIAO Hailong from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) identified hepatocellular carcinoma (HCC) subtypes with distinctive metabolic phenotypes through bioinformatics and machine learning methods, and elucidated the potential mechanisms based on a metabolite-protein interaction network and multi-omics data.

The study, published in Advanced Science on July 11, provides insights guiding precise personalized HCC medicine.

Metabolic reprogramming, which can promote rapid cell proliferation by regulating energy and nutrient metabolism, is considered to be one hallmark of cancer. It can impact other biological processes through complex metabolite-protein interactions.

The researchers utilized complex network and machine learning methods to analyze multi-omics data and the metabolite-protein interaction network to identify hepatocellular carcinoma subtypes with significant differences in prognosis.

They identified a metabolic HCC subtype with poor prognosis, which is strongly correlated with hypoxia, hypermethylation of metabolic enzymes, down-regulation of various metabolic pathways, and accumulation of multiple fatty acids. In addition, many immune-related pathways were significantly up-regulated in this poor prognosis subtype.

Based on further analyses of metabolite-protein interactions, the researchers predicted multiple interactions between unsaturated fatty acid and immunoregulatory proteins, suggesting that unsaturated fatty acid accumulation may be one potential cause of immune pathway up-regulation.

Children living in urban areas with high levels of air pollution, noise and traffic may be at higher risk of childhood obesity, according to a study by the Barcelona Institute for Global Health (ISGlobal)--a centre supported by the "la Caixa" Foundation--and the University Institute for Primary Care Research Jordi Gol (IDIAP Jordi Gol). The study was funded by the La Marató de TV3 Foundation.

Published in Environment International, the study analysed data on 2,213 children aged 9 to 12 years in the city of Sabadell (Barcelona) who were participating in the ECHOCAT and INMA projects. Forty percent of the children were overweight or obese. The researchers investigated the association between urban factors that the children were exposed to between October 2017 and January 2019 (ambient air pollution, green spaces, built environment, density of unhealthy food establishments, road traffic and road traffic noise) and various measures of childhood obesity (body mass index, waist circumference and body fat) and weight-related behaviours (fast food and sugar-sweetened beverage consumption, physical activity, sedentary behaviour, sleep duration and well-being).

To date, few studies have assessed whether the urban environment influences children's behaviours in order to better understand the relationship between this environment and the risk of childhood obesity. An understanding of the mechanisms of this relationship will facilitate the development of community-level health promotion programmes to encourage healthier behaviours in the city. Another novel aspect of this study is that it assessed multiple urban exposures together, in accordance with the concept of exposome or the study of multiple simultaneous environmental factors.

Possible Mechanisms

"Higher levels of air pollution, traffic and noise were associated with higher body mass index and a higher likelihood of the child being overweight or obese," explained lead author Jeroen de Bont, a researcher at ISGlobal and IDIAP Jordi Gol. Although the mechanisms that could explain this association remain unknown, the scientific team proposed various hypotheses. Air pollution could disrupt the molecular mechanisms that cause obesity by inducing inflammation or oxidative stress, hormone disruption and visceral adiposity (although the studies published to date have been performed in mice). Noise could influence sleep deprivation and increase stress hormones, which are associated with physical development in childhood and could increase the risk of becoming overweight.

The findings were consistent with those obtained in the same study when some environmental exposures were analysed separately. In particular, the number of unhealthy food establishments in an area was also found to be associated with childhood obesity, probably because such an environment may favour higher fast food consumption and higher caloric intake.

The study did not, however, find an association between the urban environment and the level of physical activity, sedentary behaviour and other weight-related behaviours in children, although it is thought that such factors could play a role. (For example, in areas with a good public transport network and nearby facilities and shops, journeys tend to be made on foot or by bicycle, which increases children's physical activity.) The fact that the study did not find an association between these factors could be attributed to "the difficulty of determining to what extent obesity itself influences weight-related behaviours," explained de Bont. Moreover, information on children's physical activity was collected using a questionnaire that did not take into account where the activities took place. "We were able to find out if the children played basketball or football, but not if they cycled in nearby green spaces, for example," he added.

Finally, "socioeconomic status plays an important role in the association between the urban environment and childhood obesity that is not yet clear," commented last author Martine Vrijheid, a researcher at ISGlobal. In this study, children living in more deprived areas on the outskirts of the city had higher rates of overweight and obesity even though they were exposed to lower levels of air pollution, road traffic and noise and had access to more green spaces. Further research is needed to shed light on this issue.

RUDN University mathematicians have developed a model for calculating the density of 5G stations needed to achieve the required network parameters. The results are published in Computer Communications.

Network slicing (NS) is one of the key technologies that the new 5G communication standard relies on. Several virtual networks, or layers, are deployed on the same physical infrastructure (the same base stations). Each layer is allocated to a separate group of users, devices, or applications. To slice the network, one need the NR (New Radio) technology, which operates on millimetre waves. Most of the research in this area is aimed at creating an infrastructure of NR stations that would provide network slicing in each specific case. RUDN University mathematicians have developed a first general theoretical approach that helps to calculate the density of NR base stations needed to slice the network with the specified parameters of the quality of service.

"The concept of network slicing will drastically simplify the market entrance for mobile virtual network operators as well as provisioning of differentiated quality to network services. This functionality is a major paradigm shift in the cellular world enabling multi-layer network structures similar to that of the modern Internet and allowing resource sharing with logical isolation among multiple tenants and/or services in multi-domain context", said Ekaterina Lisovskaya, PhD,
junior Researcher at the Research Center for Applied Probability & Stochastic Analysis at RUDN University.

When constructing the algorithm, the RUDN mathematicians used a model city. NR base stations were distributed with some density. The stations had three antennas, each of which covered 120 degrees. Users of devices with 5G cellular communication network operating in the millimetre frequency range (30-100 GHz) were randomly distributed around the city. They moved and could block each other's line-of-sight with the base station. Each antenna had an effective range, where the connection doesn't break even if the line-of-sight is blocked. The RUDN University mathematicians constructed the dependence of the network characteristics on the density of the station location.

To check the accuracy of the constructed model, mathematicians used a computer simulation. The results of theoretical and experimental calculations agreed. The model shows, for example, how the density of the stations affects the regime of network splitting from full isolation to full mixing. The first one assumes that each layer has its own frequency range of a fixed width. In the second regime, the frequencies of the layers are mixed with each other. The second option is more difficult from a technical point of view, but it increases the efficiency of using physical network resources. RUDN University mathematicians have studied these regimes as two boundary versions of the network implementation -- in real life, some intermediate implementation is usually required. It turned out that the difference in the density of stations between these bounds is small -- one station per 10,000 square meters.

"Our numerical evaluation campaign reveals that the full isolation and full mixing systems' operational regime changes rather abruptly with respect to the density of NR BSs. However, the system parameters may drastically affect the required density. Practically, it implies that at the initial market penetration phase, the full isolation strategy can be utilized without compromising the network performance. However, at mature deployment phases, more sophisticated schemes may reduce the capital expenditures of network operators" said Ekaterina Lisovskaya, PhD,
junior Researcher at the Research Center for Applied Probability & Stochastic Analysis at RUDN University.

Tel Aviv University's new and groundbreaking technology inspires hope among people who have lost their sense of touch in the nerves of a limb following amputation or injury. The technology involves a tiny sensor that is implanted in the nerve of the injured limb, for example in the finger, and is connected directly to a healthy nerve. Each time the limb touches an object, the sensor is activated and conducts an electric current to the functioning nerve, which recreates the feeling of touch. The researchers emphasize that this is a tested and safe technology that is suited to the human body and could be implanted anywhere inside of it once clinical trials will be done.

The technology was developed under the leadership of a team of experts from Tel Aviv University: Dr. Ben M. Maoz, Iftach Shlomy, Shay Divald, and Dr. Yael Leichtmann-Bardoogo from the Department of Biomedical Engineering, Fleischman Faculty of Engineering, in collaboration with Keshet Tadmor from the Sagol School of Neuroscience and Dr. Amir Arami from the Sackler School of Medicine and the Microsurgery Unit in the Department of Hand Surgery at Sheba Medical Center. The study was published in the prestigious journal ACS Nano.

The researchers say that this unique project began with a meeting between the two Tel Aviv University colleagues - biomedical engineer Dr. Maoz and surgeon Dr. Arami. "We were talking about the challenges we face in our work," says Dr. Maoz, "and Dr. Arami shared with me the difficulty he experiences in treating people who have lost tactile sensation in one organ or another as a result of injury. It should be understood that this loss of sensation can result from a very wide range of injuries, from minor wounds - like someone chopping a salad and accidentally cutting himself with the knife - to very serious injuries. Even if the wound can be healed and the injured nerve can be sutured, in many cases the sense of touch remains damaged. We decided to tackle this challenge together, and find a solution that will restore tactile sensation to those who have lost it."

In recent years, the field of neural prostheses has made promising developments to improve the lives of those who have lost sensation in their limbs by implanting sensors in place of the damaged nerves. But the existing technology has a number of significant drawbacks, such as complex manufacturing and use, as well as the need for an external power source, such as a battery. Now, the researchers at Tel Aviv University have used state-of-the-art technology called a triboelectric nanogenerator (TENG) to engineer and test on animal models a tiny sensor that restores tactile sensation via an electric current that comes directly from a healthy nerve and doesn't require a complex implantation process or charging.

The researchers developed a sensor that can be implanted on a damaged nerve under the tip of the finger; the sensor connects to another nerve that functions properly and restores some of the tactile sensation to the finger. This unique development does not require an external power source such as electricity or batteries. The researchers explain that the sensor actually works on frictional force: whenever the device senses friction, it charges itself.

The device consists of two tiny plates less than half a centimeter by half a centimeter in size. When these plates come into contact with each other, they release an electric charge that is transmitted to the undamaged nerve. When the injured finger touches something, the touch releases tension corresponding to the pressure applied to the device - weak tension for a weak touch and strong tension for a strong touch - just like in a normal sense of touch.

The researchers explain that the device can be implanted anywhere in the body where tactile sensation needs to be restored, and that it actually bypasses the damaged sensory organs. Moreover, the device is made from biocompatible material that is safe for use in the human body, it does not require maintenance, the implantation is simple, and the device itself is not externally visible.

According to Dr. Maoz, after testing the new sensor in the lab (with more than half a million finger taps using the device), the researchers implanted it in the feet of the animal models. The animals walked normally, without having experienced any damage to their motor nerves, and the tests showed that the sensor allowed them to respond to sensory stimuli. "We tested our device on animal models, and the results were very encouraging," concludes Dr. Maoz. "Next, we want to test the implant on larger models, and at a later stage implant our sensors in the fingers of people who have lost the ability to sense touch. Restoring this ability can significantly improve people's functioning and quality of life, and more importantly, protect them from danger. People lacking tactile sensation cannot feel if their finger is being crushed, burned or frozen."

For quite some time, farmers and researchers have been focusing on how to bind carbon to soil. Doing so makes food crops more nutritious and increases yields.

However, because carbon is converted into CO2 when it enters the atmosphere, there is a significant climate benefit to capturing carbon in soil as well.

Too much carbon finds its way into the atmosphere. Should we fail to reverse this unfortunate trend, we will fail to achieve the Paris Agreement's goal of reducing greenhouse gas emissions by 40 percent by 2030, according to CONCITO, Denmark's Green Think Tank.

As such, it is important to find new ways of sequestering carbon in soil. This is where a team of researchers from the University of Copenhagen and the Technical University of Munich enter the picture.

In their new study, they argue for the potential of simply allowing agricultural crop residues to rot in fields.

"Fragments of dead plants in soil are often considered as fast food for microbes and fungi. But our study demonstrates that plant residues actually play a more significant role in forming and sequestering carbon in soil than what was once thought," explains Kristina Witzgall, a PhD Candidate at the Technical University of Munich and the study's lead author.

In the past, researchers mainly focused on carbon storage in the surfaces of minerals like clay. However, the new results demonstrate that plant residues themselves have the ability to store carbon, and perhaps for longer than once supposed.

This is because a number of important processes take place directly upon the surface of these plant remains.

"We demonstrate that agricultural crop residues are absolutely central to carbon storage and that we should use them in a much more calculated way in the future. Plant residues make it possible for carbon, in all likelihood, to be stored in soil for roughly four times longer than if they aren't added," states Carsten Müller, the study's co-author and an associate professor at the University of Copenhagen's Department of Geosciences and Natural Resource Management.

Fungi and soil clumps store carbon

To understand how plant residue sequesters carbon, it is important to know that plant tissue already contains carbon absorbed by plants from the atmosphere via photosynthesis. As plant matter rots, carbon can be transferred into the soil in a number of ways.

"Our analysis shows that plant residues, as they interact with fungi, play a surprisingly large role in carbon storage. As fungi fling their white strands around plant fragments, they 'glue' them together with the soil. The fungi then consume the carbon found in the plant matter. In doing so, they store carbon in the soil," explains Carsten Müller.

In addition to fungi, the researchers' analyses also show that the soil structure itself determines the amount of carbon that can be stored.

"When soil is glued together in large hard lumps by the stickiness of bacteria and fungi, plant residues are shielded from being consumed by bacteria and fungi, which would otherwise eat and then emit some of the carbon as CO2 into the atmosphere," says Kristina Witzgall.

She goes on to say that while carbon can be stored in soil from weeks to a thousand years, the usual duration is about 50 years.

Reducing CO2 in the future

The method of leaving crop residues like stalks, stubble and leaves to rot is not unheard of when it comes to enhancing agricultural land.

However, deploying rotten plants as a tool to store carbon should be taken more seriously and considered as a strategy to be expanded, according to the researchers behind the new study.

"The fertile and climate-friendly agricultural lands of the future should use crop residue as a way of sequestering carbon. We will also be conducting experiments where we add rotten plant matter deeper into the soil, which will allow carbon to be stored for even longer periods of time," says Carsten Müller.

If we work to create better conditions for carbon sequestration in soil, we could store between 0.8 and 1.5 gigatonnes of carbon annually. By comparison, the world's population has emitted 4.9 gigatonnes of carbon per year over the past 10 years.

All in all, the researchers' findings can be used to understand the important role and promise of crop residues for carbon storage in the future.

However, Kristina Witzgall goes on to say that a variety of initiatives are needed to increase carbon sequestration, such as crops that can absorb atmospheric carbon and the restoration of lost forests.

A Sussex team - including university mathematicians - have created a new modelling toolkit which predicts the impact of COVID-19 at a local level with unprecedented accuracy. The details are published in the International Journal of Epidemiology, and are available for other local authorities to use online, just as the UK looks as though it may head into another wave of infections.

The study used the local Sussex hospital and healthcare daily COVID-19 situation reports, including admissions, discharges, bed occupancy and deaths.

Through the pandemic, the newly-published modelling has been used by local NHS and public health services to predict infection levels so that public services can plan when and how to allocate health resources - and it has been conclusively shown to be accurate. The team are now making their modelling available to other local authorities to use via the Halogen toolkit.

Anotida Madzvamuse, professor of mathematical and computational biology within the School of Mathematical and Physical Sciences at the University of Sussex, who led of the study, said:

"We undertook this study as a rapid response to the COVID-19 pandemic. Our objective was to provide support and enhance the capability of local NHS and Public Health teams to accurately predict and forecast the impact of local outbreaks to guide healthcare demand and capacity, policy making, and public health decisions."

"Working with outstanding mathematicians, Dr James Van Yperen and Dr Eduard Campillo-Funollet, we formulated an epidemiological model and inferred model parameters by fitting the model to local datasets to allow for short, and medium-term predictions and forecasts of the impact of COVID-19 outbreaks.

"I'm really pleased that our modelling has been of such value to local health services and people. The modelling approach can be used by local authorities to predict the dynamics of other conditions such as winter flu and mental health problems."

Professor Anjum Memon, Chair in Epidemiology and Public Health Medicine at BSMS and co-author of the study, said:

"The world is in the cusp of experiencing local and regional hotspots and spikes of COVID-19 infections. Our epidemiological model, which is based on local data, can be used by all local authorities in the UK and other countries to inform healthcare demand and capacity, emergency planning and response to the supply of medications and oxygen, formulation, tightening or lifting of legal restrictions and implementation of preventive measures."

"The model will also serve as an excellent tool to monitor the situation after the legal COVID-19 restrictions are lifted in England on 19 July, and during winter months with competing respiratory infections."

Kate Gilchrist, Head of Public Health Intelligence at Brighton & Hove City Council and co-author of the study, said:

"This unique piece of work demonstrated that by using local datasets, model predictions and forecasting allowed us to plan adequately the healthcare demand and capacity, as well as policy-making and public health decisions to mitigate the impact of COVID-19 on the local population. Understanding how future COVID-19 spikes and waves could possibly affect the local populations empowers us to ensure that contingency measures are in place and the timely commissioning and organisation of services."

Dr Sue Baxter, Director of Innovations and Business Partnerships at the University of Sussex, said:

"The University is delighted that this innovative modelling approach and philosophy has been translated from the mathematical drawing board into a web-based tool-kit called Halogen, which can be used by NHS hospitals, local authorities and public health departments locally and across the UK to help save lives and improve capability for hard pressed public health workers. The successful commercialisation of this kind of innovation illustrates just one of the transformational impacts that the Higher Education Innovation Fund can make when applied in a targeted way."

The impact of El Nino on East Asian climate under a warmer climate will be dominated by the change in El Nino decaying pace, according to a new paper published by a research team based in the Institute of Atmospheric Physics, Chinese Academy of Sciences, China.

The western North Pacific anomalous anticyclone (WNPAC) is a low-level atmospheric circulation system, linking up El Nino events with East Asian -western Pacific summer climate. The WNPAC can persist from El Nino mature phase in boreal winter to the upcoming summer, bringing abundant moisture to enhance the precipitation over East Asia. How the WNPAC will change in the future concerns millions of people living in the East Asian -western Pacific region, but the future change in the WNPAC under global warming is highly uncertain across climate models.

The study, which appears in Journal of Climate online on 5th June, found that about 23% of the uncertainty in WNPAC projection is attributed to the El Nino amplitude change while the rest 77% is from non-amplitude change which is mainly related to the change in El Nino decaying pace, according to Tianjun Zhou, the corresponding author of the paper.

Zhou is a senior scientist at the Institute of Atmospheric Physics in the Chinese Academy of Sciences. He is also a professor at the University of Chinese Academy of Sciences (UCAS).

"To separately quantify the contributions of El Nino amplitude change and non-amplitude change from the total uncertainties, we have developed a new decomposition method. This decomposition method is based on large ensemble climate simulation. We have used the output of 40-member large ensemble from the Community Earth System Model Large Ensemble project", said Mingna Wu, the first author of the study, who is a Ph. D student from the UCAS.

"A larger El Nino amplitude can enhance the WNPAC through a stronger tropical Indian Ocean capacitor effect under a warmer climate, while a faster El Nino decaying pace can also enhance the WNPAC through descending Rossby waves in response to colder than normal sea surface temperature over the tropical central-eastern Pacific, and vice versa", explained Dr. Xiaolong Chen, co-author of the study, and an associated professor at the Institute of Atmospheric Physics, Chinese Academy of Sciences.

"In addition to El Nino amplitude, more attention should be paid to the influence of other El Nino characteristics (i.e. El Nino decaying pace) in climate system. Our decomposition method can be used to diagnose the origin of uncertainty related to El Nino in climate projections, as well as the relevant mechanisms." Highlighted Wu.

Ecologists from the Conservation Forensics Laboratory of the Research Division for Ecology and Biodiversity at the University of Hong Kong (HKU) have applied stable isotope techniques to determine whether birds in the pet trade are captive or wild-caught, a key piece of evidence required in many cases to determine whether a trade is legal or not. They have applied this technique to the yellow-crested cockatoo (Cacatua sulphurea, YCC), a critically endangered species from Indonesia/Timor-Leste with a global population of fewer than 2,500, according to the International Union for the Conservation of Nature (IUCN). Threatened by overexploitation for the pet trade, Hong Kong has a sizeable population of 150-200 individuals which was established through the release of birds transported here as pets.

There is a global ban on trapping and international trade of wild-caught YCCs; the species has been listed on Appendix I of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) since 2005. In Hong Kong, it is legal in some cases to sell captive-bred birds, however it is difficult to differentiate a wild-caught from a captive-bred cockatoo just by eye - which means illegally caught YCCs can be laundered in the legal market by claiming they have been bred in captivity.

Wild or captive?

Yellow-crested cockatoos are commonly sold as pets in Hong Kong. Dr Astrid ANDERSSON from the Conservation Forensics Laboratory conducted a market survey at Yuen Po Street bird market in Mong Kok from 2017-2018 and observed 33 unique individual YCCs for sale during this period, more than have officially been imported to Hong Kong since 2005 (10 individuals). These birds could have been bred by home breeders (which is a legal grey area in Hong Kong), trafficked from abroad (illegal) or taken from Hong Kong's free-flying, introduced population of YCCs (illegal). In order to determine whether birds in trade are legal or not, there is a need for a method for determining whether an individual is sourced from the wild or captive-bred.

Under the supervision of Dr Caroline DINGLE, Director of Conservation Forensics Laboratory, Dr ANDERSSON conducted stable isotope analysis(SIA) and compound-specific stable isotope analysis(CSIA) on feathers from Hong Kong's wild YCC population and on feathers from pet cockatoos owned by private individuals to see if differences in the diet of captive and wild birds were reflected in carbon and nitrogen values. The team applied two novel forensic tools: stable isotope analysis (SIA) as the basic first step and compound-specific stable isotope (CSIA), which analyses isotope values associated with specific amino acids, as the advanced second step. They found that both stable carbon and nitrogen isotope values differed significantly between wild and captive cockatoos, indicating consumption of different plant and protein types in their diets. They also found that the isotopes associated with six amino acids differed significantly - with valine being the most informative.

Enforcement officials could apply this test in the future to determine whether a cockatoo has been raised in the wild or in captivity.

"Legal wildlife trade creates opportunities for the sale of illegally procured wildlife since it is difficult to discern legal from laundered items. This problem is common across many wildlife trade areas - exotic pets, ornaments, seafood -- and involves a variety of taxa. Our results show that SIA, together with CSIA, presents a powerful tool for government authorities in their efforts to regulate wildlife trade," said Dr Astrid Andersson, the first author of the study.

"The successful and novel application of CSIA as a secondary validation step to increase the accuracy of SIA for detecting wild vs captive individuals is promising and adds to the growing volume of research that demonstrates the applicability of stable isotope techniques in wildlife forensics. While more work needs to be done to validate SIA as a robust forensic test, the results from this study show that this is a promising avenue for continued research," added Dr Caroline Dingle.

July 12, 2021-- A new study sheds light on how the specter of dementia and chronic pain reduce people's desire to live into older ages. Among Norwegians 60 years of age and older the desire to live into advanced ages was significantly reduced by hypothetical adverse life scenarios with the strongest effect caused by dementia and chronic pain, according to research conducted at the Robert N. Butler Columbia Aging Center based at the Columbia Mailman School of Public Health.

The paper is among the first to study Preferred Life Expectancy (PLE) based on hypothetical health and living conditions. The findings are published in the July issue of the journal Age and Ageing.

The research team was led by Vegard Skirbekk, PhD, professor of Population and Family Health, who used data from Norway, because of its relatively high life expectancy at birth. He investigated how six adverse health and living conditions affected PLE after the age of 60 and assessed each by age, sex, education, marital status, cognitive function, self-reported loneliness and chronic pain.

The analysis included data from the population-based NORSE-Oppland County study of health and living conditions based on a representative sample of the population aged 60-69 years, 70-79 years and 80 years and older. The data collection was done in three waves in 2017, 2018 and 2019. A total of 948 individuals participated in the interviews and health examinations.

Skirbekk and colleagues asked the 825 community dwellers aged 60 and older the question, "If you could choose freely, until which age would you wish to live?" The results showed that among Norwegians over 60, the desire to live into advanced ages was significantly reduced by hypothetical adverse life scenarios, such as effects of dementia and chronic pain. Weaker negative PLE effects were found for the prospect of losing one's spouse or being subject to poverty

According to Skirbekk, "Dementia tops the list of conditions where people would prefer to live shorter lives - which is a particular challenge given the rapid increase in dementia in the years ahead."

The average Preferred Life Expectancy was 91.4 years of age and there was no difference between men and women, but older participants had higher PLE than younger participants. PLE among singles was not affected by the prospect of feeling lonely. The higher educated had lower PLE for dementia and chronic pain.

"Despite the fact that rising life expectancy to a large extent occurs at later ages, where the experience of loss and disability are widespread, there had been remarkably little scientific evidence on how long individuals would like to live given the impact of such adverse life conditions,' noted Skirbekk.

Ants are omnipresent, and we often get blisters after an ant bite. But do you know the molecular mechanism behind it? A research team led by Professor Billy K C CHOW from the Research Division for Molecular and Cell Biology, Faculty of Science, the University of Hong Kong (HKU), in collaboration with Dr Jerome LEPRINCE from The Institut national de la santé et de la recherche médicale (INSERM) and Professor Michel TREILHOU from the Institut National Universitaire Champollion in France, have identified and demonstrated a novel small peptide isolated from the ant venom can initiate an immune pathway via a pseudo-allergic receptor MRGPRX2. The study has recently been published in a top journal in Allergy - The Journal of Allergy and Clinical Immunology.

Allergy is a common undesirable immune response for most people, and are often caused by allergens such as food, pollen, drugs, mites, bites and stings from venomous insects etc. When an allergic reaction happens, mast cells that line the body surfaces alert the immune system by releasing cytokines. Thus, other immune cells are recruited to the infected area to clear the allergens.

There are two kinds of allergic reaction: allergic and pseudo allergic reactions. Allergic reactions are triggered when allergens bind to the high-affinity IgE receptor on mast cells, whereas the pseudo allergic reactions are majorly triggered when allergens bind to MRGPRX2 on mast cells. Therefore, different medical treatments are required to contain them.

Recently, the discovery of IgE and MRGPRX2 expressed receptors in mast cells has helped us to understand the root cause of most allergic and pseudo allergic reactions. However, functional characterisation of MRGPRX2 is very limited since it has not got much attention in the allergic field as a pseudo allergic receptor until recently, whereas the former is very well studied. The function of MRGPRX2, other than being a pseudo allergic receptor, is largely unknown and yet to be explored.

For instance, pseudo allergic reactions can be induced by various FDA approved drugs. So, understanding this pseudo allergic mechanisms will help in developing drugs without side effects. In addition, understanding of pseudo allergic reactions will also help in developing antagonists that would minimise clinically relevant MRGPRX2 mediated allergic reactions such as rosacea or red man syndrome.

Through concerted efforts, our research team identifies and demonstrates a naturally abundant venom peptide from ants that activates a previously unknown pseudo allergic pathway, which in turn, help to discover other function of MRGPRX2, sheding light on the non-pseudo allergic function of MRGPRX2.

Research background

Insect venoms are biochemical arsenals developed by animals to defend themselves. Interestingly, arthropods contain the maximum number of species capable of making venoms that can produce biological effects in our body. Particularly, ants are the most dominant and diversified species with more than 14,700 known species and the biggest biomass in most territorial ecosystems. Therefore, Insect venoms are very important resources for us containing a treasure of biologically active chemicals, peptides and proteins. For instance, Purotoxin-1 (PT1), Apamin and Bicarinalin are bioactive peptides isolated from various insect venoms that are known to play a role in inflammatory pain, antimicrobial effects and cytotoxic effects against cancer cells.

P17 is a short host defence peptide isolated from the venom of an ant Tetramorium bicarinatum. We have recently demonstrated its involvement in our body defence system via interacting with an unknown receptor to activate the immune system to kill the fungal infection in mice lungs. P17, therefore can be exploited as a therapeutic peptide for inflammatory disorders or cancer and pseudo allergic reactions. In this study, after screening almost the entire human G protein-coupled receptor repertoire, we have successfully identified a specific human receptor or Mas-related G protein-coupled receptor-X2 (MRGPRX2) that is responsible for interacting with P17 to carry out its activity.

Key findings

The research team has extensively worked on identifying a lock (GPCR) for a key (P17) by trying about 400 locks for a single key and eventually identified the GPCR for P17. In addition, we also demonstrated the molecular pathways of P17-MRGPRX2 mediated activation of mast cells, an immune cell that is responsible for the allergic reaction. Upon deorphanising of P17, we then used computational approaches to find the important amino acids (ridges in the key) that are important for the binding of the venom peptide with its receptor - like a key ridge in the key for a lock.

Our team then uncovered a novel pathway for this receptor. We showed P17 induces infiltration of monocytes at the injected site by activating MRGPRX2. The effect is quite similar to an ant bite in humans. Once the ant bites you, you will have blisters/swelling, which indicates the immune cell infiltration at the bite site to remove the ant venom. Usually, our body detects the external substances (arrows in the diagram) via receptors (targets) and act upon those external substances to clear them out. In this scenario, P17 is the arrow detected by MRGPRX2 of mast cells to recruit monocytes and differentiates them into macrophages to engulf and clear the pathogens. To the best of our knowledge, we demonstrated for the first time that MRGPRX2 mediated activation of mast cell could recruit human monocyte and differentiate them into macrophages. This study shows a novel immunomodulatory effect of MRGPRX2 and suggests that it is a vital receptor in innate immunity.

Societal impact of the findings

Firstly, a novel immunomodulatory pathway of MRGPRX2 has been demonstrated, which could enhance the overall understanding of the receptor function among the scientific community. Additionally, Macrophages are specialised cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms. Thus, using this novel information, we can design new analogues that are agonists or antagonists of MRGPRX2 to modify our immune response to deal with host defence, allergic or other immune diseases.

"We demonstrated that peptides isolated from venoms can be used to modulate immune responses and these peptides are abundant in nature. One key message we should take from this finding is biodiversity is one of the greatest treasure we have and we just have to use them wisely," said Professor Chow. "Our findings are evident that novel scientific innovations come from observing the nature. Ant bite leads to immune cell infiltration, so we just isolated the peptide that recruits the immune cells that can be beneficial," said Dr Duraisamy. Besides, the HKU team's laboratory has established a platform for translating basic biology into novel drug discoveries as we already have filed a patent for the design and synthesis of a group of drugs with high efficacies to translate them into societal impact. Using this novel pathway we could eventually tweak it a bit to our benefit to kill off pathogens during infection.

Research Team

The research was conducted by the team led by Professor Billy KC CHOW from the Research Division for Molecular and Cell Biology. Dr Karthi DURAISAMY from Professor Chow's group is the first author of the paper, while Dr Jérôme LEPRINCE is the co-corresponding author of the paper. Professor Michel TREILOU, Dr Elsa BONNAFÉ, Dr Kailash SINGH, Mr Benjamin LEFRANC and Mr Mukesh KUMAR contributed to the research.

Through a complex, self-reinforcing feedback mechanism, colorectal cancer cells make room for their own expansion by driving surrounding healthy intestinal cells to death - while simultaneously fueling their own growth. This feedback loop is driven by an activator of the innate immune system. Researchers from the German Cancer Research Center (DKFZ) and the University of Heidelberg discovered this mechanism in the intestinal tissue of fruit flies.

Maintaining the well-functioning state of an organ or tissue requires a balance of cell growth and differentiation on the one hand, and the elimination of defective cells on the other. The intestinal epithelium is a well-studied example of this balance, termed "tissue homeostasis": Stem cells in the intestinal crypts constantly produce progenitor cells that further differentiate to replace the rapidly deteriorating mature cells of the intestinal mucosa.

Growth requires a constant dynamic reorganization of tissue architecture: Defective cells must be displaced from the tissue, also by mechanical forces. Tumor cells disrupt this finely balanced structure: They aggressively make room for their own expansion. Until now, it was not understood how exactly they do this.

Jun Zhou, Erica Valentini and Michael Boutros from the German Cancer Research Center and the University of Heidelberg have now investigated these processes in the intestinal epithelium of the fruit fly, which has a similar structure to the intestine of mammals. By blocking the important BMP signaling pathway, the researchers triggered numerous tumors in the fly intestine. Using this model, they uncovered how cancer cells accelerate their own growth through a sophisticated, self-reinforcing feedback effect.

First, tumor cells tear apart the tissue structure by acting on cell adhesion. The resulting altered mechanical adhesion of the intestinal cells activates a stress-sensitive signaling pathway in neighboring intestinal cells, which in turn causes the activation og genes that promote programmed cell death (apoptosis): The team was able to detect large amounts of proteins that initiate aopotosis in the intestinal cells surrounding individual tumor cells.

Presumably due to cytokines released by dying intestinal cells, the growth-promoting JAK/Stat signaling pathway is activated in tumor cells, leading to further tumor spread.

The team also found that the immune activator PGRP-LA is required for this process. When PGRP-LA is turned off, fewer colon cells die through apoptosis and tumor growth also slows down. "The colon cancer cells apparently hijack a signaling molecule of the innate immune system and misuse it for their own purposes. In this way, they kill two birds with one stone: they make room for their expansion by eliminating intestinal cells in their environment - and additionally fuel their own growth," explains study leader Michael Boutros. Future studies will determine whether the same mechanisms also play a role in the spread of human intestinal tumors.

Chemotherapy is widely used to treat cancer patients. During the treatment, chemotherapeutic agents affect various biochemical processes to kill or reduce the growth of cancer cells, which divide uncontrollably in patients. However, the cell-damaging effect of chemotherapy affects cancer cells but also in principle many other cell types, including cycling blood cells. This puts the hematopoietic system under severe stress and pushes hematopoietic stem cells (HSCs) in the bone marrow to produce fresh cells and replenish the stable pool of differentiated blood cells in the body.

Researchers from the MPI of Immunobiology and Epigenetics, together with colleagues from the University of Freiburg, Lyon, Oxford, and St Jude Children's Research Hospital in Memphis, now discovered that hematopoietic stem cells make use of RNA molecules from junk DNA sections to enhance their activation after chemotherapy.

Wake-up inflammation for HSC

Hematopoietic stem cells lie on the top of the hematopoietic hierarchy and can give rise to the majority of blood cells including immune cells. Under normal conditions, HSCs kept dormant in the bone marrow to preserve their long-term self-renewal potential and prevent stem cell exhaustion. However, upon chemotherapy, they are "forced" to exit quiescence and start cycling. "Hematopoietic stem cells respond to chemotherapy by starting proliferating. We know that inflammatory signaling is pivotal for HSC activation but we still don't understand completely how this happens", says Eirini Trompouki, group leader at the MPI of Immunobiology and Epigenetics in Freiburg.

A link between chemotherapy-induced inflammation and junk RNA

Interestingly, she and her team observed that other RNA molecules besides the RNAs of "classic" coding genes are transcribed in HSCs after chemotherapy. A part of these RNAs stems from active or inactive transposable elements. Transposable elements are remnants of pathogens such as viruses or bacteria that have been integrated into the genome through millions of years of evolution. Researchers often considered these extensive strands of genetic material that dominate the human and mouse genome by more than one-third but seem to lack specific functions, as "junk DNA."

Once the team noticed that RNA from these elements is increased after chemotherapy, the question then became: "Is there a link between transposable element RNA and the increased inflammatory signals observed after chemotherapy?" explains Thomas Clapes, lead author in the study. Indeed, HSCs express some receptors that could induce inflammation but they are primarily associated with immune cells and their role is to sense viral RNA. "We hypothesized that these receptors could also bind to transposable element RNA," says Aikaterini Polyzou. The data of the scientists show that transposable element RNA can bind to the immune receptor MDA5 and trigger an inflammatory response that results in HSCs exiting quiescence and starting to proliferate. "Without these interactions, HSC activation becomes slower and less efficient. This indicates that RNA sensing is probably not necessary for hematopoietic regeneration but helps to enhance blood regeneration after chemotherapy," say Thomas Clapes, Aikaterini Polyzou and Pia Prater.

Mechanism or adaptation?

These findings help to better understand the molecular underpinnings of hematopoietic regeneration, especially after chemotherapy. However, the results also pinpoint that transposable element RNA is used by the cells during developmental transitions. The transition of a cell from an inactive-quiescent to an active proliferative state means a massive reorganization of the genome. For example, the cell needs to switch off genes responsible for the energy-saving mode and turns on genes essential for increased metabolism or cell cycling. "It is interesting to think that cells make use of transposable elements or other repetitive RNAs to finetune and adapt whenever they need to change their state for example after stress, like chemotherapy or even after physiological stress signals like development or aging," says Eirini Trompouki. The scientists assume that the usage of RNA is a way for the cell to sense and buffer transcription. "We have many more things to find out to be able to understand if RNA sensing is an evolutionary adaptation used in cases of high cellular plasticity to finetune cell fate decisions," says Eirini Trompouki.

Proteomics produces enormous amounts of data, which can be very complex to analyze and interpret. The free software platform MaxQuant has proven to be invaluable for data analysis of shotgun proteomics over the past decade. Now, Jürgen Cox, group leader at the Max Planck Institute of Biochemistry, and his team present the new version 2.0. It provides an improved computational workflow for data-independent acquisition (DIA) proteomics, called MaxDIA. MaxDIA includes library-based and library-free DIA proteomics and permits highly sensitive and accurate data analysis. Uniting data-dependent and data-independent acquisition into one world, MaxQuant 2.0 is a big step towards improving applications for personalized medicine.

Proteins are essential for our cells to function, yet many questions about their synthesis, abundance, functions, and defects still remain unanswered. High-throughput techniques can help improve our understanding of these molecules. For analysis by liquid chromatography followed by mass spectrometry (MS), proteins are broken down into smaller peptides, in a process referred to as "shotgun proteomics". The mass-to-charge ratio of these peptides is subsequently determined with a mass spectrometer, resulting in MS spectra. From these spectra, information about the identity of the analyzed proteins can be reconstructed. However, the enormous amount and complexity of data make data analysis and interpretation challenging.

Two ways to analyze proteins with mass spectrometry

Two main methods are used in shotgun proteomics: Data-dependent acquisition (DDA) and data-independent acquisition (DIA). In DDA, the most abundant peptides of a sample are preselected for fragmentation and measurement. This allows to reconstruct the sequences of these few preselected peptides, making analysis simpler and faster. However, this method induces a bias towards highly abundant peptides. DIA, in contrast, is more robust and sensitive. All peptides from a certain mass range are fragmented and measured at once, without preselection by abundance.

As a result, this method generates large amounts of data, and the complexity of the obtained information increases considerably. Up to now, identification of the original proteins was only possible by matching the newly measured spectra against spectra in libraries that comprise previously measured spectra.

Combining DDA and DIA into one world

Jürgen Cox and his team have now developed a software that provides a complete computational workflow for DIA data. It allows, for the first time, to apply algorithms to DDA and DIA data in the same way. Consequently, studies based on either DDA or DIA will now become more easily comparable. MaxDIA analyzes proteomics data with and without spectral libraries. Using machine learning, the software predicts peptide fragmentation and spectral intensities. Hence, it creates precise MS spectral libraries in silico. In this way, MaxDIA includes a library-free discovery mode with reliable control of false positive protein identifications.

Furthermore, the software supports new technologies such as bootstrap DIA, BoxCar DIA and trapped ion mobility spectrometry DIA. What are the next steps? The team is already working on further improving the software. Several extensions are being developed, for instance for improving the analysis of posttranslational modifications and identification of cross-linked peptides.

Enabling researchers to conduct complex proteomics data analysis

MaxDIA is a free software available to scientists all over the world. It is embedded in the established software environment MaxQuant. "We would like to make proteomics data analysis accessible to all researchers", says Pavel Sinitcyn, first author of the paper that introduces MaxDIA. Thus, at the MaxQuant summer school, Cox and his team offer hands-on training in this software for all interested researchers. They thereby help bridging the gap between wet lab work and complex data analysis.

Sinitcyn states that the aim is to "bring mass spectrometry from the Max Planck Institute of Biochemistry to the clinics". Instead of measuring only a few proteins, thousands of proteins can now be measured and analyzed. This opens up new possibilities for medical applications, especially in the field of personalized medicine.

The transportation sector is the largest contributor to greenhouse gas emissions in the United States, and a lot of attention has been devoted to electric passenger vehicles and their potential to help reduce those emissions.

But with the rise of online shopping and just-in-time shipping, electric delivery fleets have emerged as another opportunity to reduce the transportation sector's environmental impact.

Though EVs represent a small fraction of delivery vehicles today, the number is growing. In 2019, Amazon announced plans to obtain 100,000 electric delivery vehicles. UPS has ordered 10,000 of them and FedEx plans to be fully electric by 2040.

Now, a study from University of Michigan researchers shows that when, where and how those fleet vehicles are charged can greatly impact their potential to reduce greenhouse gas emissions.

A key point of the study is that both the emissions directly tied to charging the vehicles and emissions that result from manufacturing the batteries must be considered. Charging practices that shorten a battery's lifetime will lead to early battery replacement, adding to the total greenhouse gas emissions associated with that vehicle.

The U-M researchers found that 50% to 80% of the lifetime emissions associated with an electric delivery vehicle's battery occur during charging. Therefore, charging from a cleaner energy source--such as an electrical grid with lots of renewables--is one of the most impactful ways to lower the emissions of an electric vehicle.

When both charging and battery degradation were considered, the researchers found that greenhouse gas emissions could be lowered by as much as 37% by optimizing charging strategies.

And, surprisingly, they also found that even in the most carbon-intensive regions of the United States, electric delivery vehicles resulted in fewer greenhouse gas emissions than their gasoline or diesel counterparts.

"Our evaluation strategy leads to two main recommendations for companies investing in fleets of electric vehicles," said Maxwell Woody of U-M's Center for Sustainable Systems, lead author of the study published online July 9 in the journal Environmental Science & Technology.

"The first is to consider battery degradation when determining when to charge and how much to charge. Some charging strategies can extend battery lifetime, and this will both lower greenhouse gas emissions and protect the company's investment."

The U-M team's second recommendation to fleet owners is to consider where the energy charging the vehicle comes from. A vehicle charged from solar or wind energy and a vehicle charged from a coal- or natural gas-fired power plant will have very different environmental impacts.

"Considering the charging source can help companies determine the best places to charge, as local grids vary across the country. Companies should prioritize fleet electrification in regions that provide the greatest carbon-reduction benefits," said Woody, a recent master's graduate of U-M's School for Environment and Sustainability who now works as a research area specialist at the Center for Sustainable Systems.

In their modeling study, the researchers analyzed four charging strategies and looked at their lifetime environmental impacts. The new U-M study goes beyond previous work by combining the regional and temporal variation in charging emissions with the impact of charging on battery degradation.

The researchers showed that a baseline charging scenario in which a vehicle is fully charged immediately upon returning to a central depot resulted in the highest emissions. Employing alternative charging methods led to emissions reductions of 8% to 37%.

"Charging the vehicle as soon as it returns and charging the vehicle up to 100% result in a lot of time spent sitting at the depot/charging station with a full battery. This extra time spent fully charged will cause the battery to wear out more quickly--so quickly that the battery may need to be replaced sometime in the vehicle's lifetime," said study corresponding author Parth Vaishnav, assistant professor at the U-M School for Environment and Sustainability.

"Creating this additional battery produces additional greenhouse gas emissions, as well as additional costs."

Charging the battery only enough to complete the day's route, a practice the researchers called sufficient charging, led to a large increase in battery lifetime--in some cases more than doubling it. As a result, emissions tied to battery production were reduced.

Overall, charging strategies that minimized greenhouse gas emissions typically lowered costs as well. In most cases, delaying charging until the vehicle was close to departure, combined with sufficient charging, was the optimal strategy for both cost and emissions.

"The most important finding is that there is a big opportunity here to lower emissions," said study co-author Greg Keoleian, U-M professor of environment and sustainability and director of the U-M Center for Sustainable Systems.

"Electric delivery vehicles only make up a small proportion of delivery vehicles right now, but that number is expected to increase in the coming years. Establishing the best practices for charging now, as these vehicles are starting to be deployed in larger numbers, is a critical step toward lowering greenhouse gas emissions."

Recall a phone number or directions just recited and your brain will be actively communicating across many regions. It is thought that working memory relies on interactions between these regions, but how these brain areas interact and properly represent memory has remained a mystery.

At Baylor College of Medicine, Dr. Nuo Li, assistant professor of neuroscience and a McNair Scholar, and his colleagues investigated the nature of the communication between brain regions involved in working memory and found evidence that a modular network organization is critical for persistent neural activity.

How brain regions communicate

Li and his colleagues were able to see that each hemisphere of the brain has a separate representation of a memory. However, the hemispheres are tightly coordinated on a moment-to-moment basis, resulting in highly coherent information across them during working memory.

In their study, the researchers engaged mice in a simple behavior that would require them to store specific information. They were trained to delay an instructed action for a few seconds. This time delay gave researchers the chance to look at brain activity during the memory process.

"We saw many neurons simultaneously firing from both hemispheres of the cortex in a coordinated fashion. If activity went up in one region, the other region followed closely. We hypothesized that the interactions between brain hemispheres is what was responsible for this memory," Li said.

Li and his colleagues recorded activity in each hemisphere, showing that each one made its own copy of information during the memory process. So how are the two hemispheres communicating?

Li explained that through the use of optogenetics they were able to corrupt information in a single hemisphere, affecting thousands of neurons during the memory period. What they found was unexpected.

"When we disrupted one hemisphere, the other area turned off communication, basically preventing the corruption from spreading and affecting activity in other regions," Li said. "This is similar to modern networks such as electricity grids. They are connected to allow for the flow of electricity but also monitor for faults, shutting down connections when necessary so the entire electrical grid doesn't fail."

In collaboration with Dr. Shaul Druckmann and Ph.D. student Byungwoo Kang at Stanford University, the researchers developed theoretical analyses and network simulations of this process, showing that this modular organization in the brain is critical for the robustness of persistent neural activity. This robustness could be responsible for the brain being able to withstand certain injuries, protecting cognitive function from distractions.

"Understanding redundant modular organization of the brain will be important for designing neural modulation and repair strategies that are compatible with the brain's natural processing of information," Li said.

Read the paper in the journal Cell.