Tech

CNIO researchers find molecular switch that allows organisms to adapt to fasting conditions

image: Fasted mouse liver, where RagA is off (left, blue) to enable a "save mode" metabolism; Fasting animals that have the RagA switch on (right, brown) cannot adapt to nutrient shortage. /CNIO

Image: 
CNIO

Getting energy and nutrients from the environment - that is, eating - is such an important function that it has been regulated through sophisticated mechanisms over hundreds of millions of years. Some of these mechanisms are only now beginning to be unravelled. A group at the Spanish National Cancer Research Centre (CNIO) has found one of their key components - a switch that controls the ability of organisms to adapt to low cellular nutrient levels.

The protein involved is RagA, which is part of the mTOR molecular pathway, whose importance in metabolic activity regulation has been known for decades now. CNIO researchers have found that if RagA is continuously activated, cells do not know that there are no sufficient nutrients and so keep on using energy as if nutrients were plentiful.

The study is published in Nature Communications this week. The corresponding author is Alejo Efeyan, Leader of the Metabolism and Cell Signalling Group at the CNIO, while Celia de la Calle is the first author.

"Today, nutrients are always abundant" Efeyan says, "but the conditions under which we evolved were very different." "Our organism adapts to feeding-fasting cycles, and our cells are prepared to respond to them. We have discovered that RagA activation is key to our adaptation to fasting conditions".

The importance of the RagA molecular pathway is on a par with that of other components that play a key role in nutrition, like insulin. However, RagA was identified not that long ago, and comparably little is known about its role in the regulation of metabolism. Understanding how the Rag proteins operate in the cell could enable us to find new strategies to fight obesity and obesity-related diseases, like fatty liver or cancer.

"Adapting to fluctuations in nutrient levels is fundamental in all living organisms," Efeyan explains. "This is an ancient molecular pathway, older than insulin actually. It is found even in yeasts. Despite this, little is known about how it affects normal physiology and how its activity is deregulated in obesity and obesity-related conditions."

'Saving mode' on

In healthy organisms, RagA detects low nutrient levels and switches off accordingly, with cell metabolism enabling an "energy-saving mode". The organism then becomes more "frugal", using the resources stored when nutrients were abundant.

When RagA is activated, mice "continue using energy; they do not adjust their metabolism to normal feeding-fasting cycles. Their cells 'believe' nutrients are abundant all the time and do not save energy," says Celia de la Calle, first author of the study.

The researchers of the Metabolism and Cell Signalling Group at CNIO had previously shown the importance of this system. Using mice embryos with permanent activation of RagA, they showed that the animals could not adapt to nutrient deficit at birth, when nutrients are no longer delivered through the placenta.

The importance of sensing fasting

In the study, the researchers prevented RagA from switching off only partially, so that the mice could survive. However, they had metabolic alterations that spanned glucose, amino acid, ketone and lipid homeostasis, among others.

The mice in the study lived around nine months, less than normal animals. The authors of the study believe this is why they could not detect signs of accelerated aging. They expected they would, since fasting and low-calorie intake increase lifespan in some species, and the mechanisms involved are associated with mTOR, the molecular pathway in which RagA participates.

In addition, the authors of the study generated adult mice with RagA activation in the liver only. Numerous effects were observed in this organ, which plays a key role in energy metabolism.

Simulating fasting benefits?

Identifying RagA as a switch in the "energy-saving mode" is the starting point of new research lines. So far, researchers have studied what happens when RagA is permanently activated: animals are never in a fasted state, and the long-term consequences are serious. But what would happen if RagA were permanently inhibited?

"We want to explore this path," Efeyan says. "With partial pharmacological inhibition of this metabolic pathway, we might get the metabolic benefits of fasting without the difficulties of limited food intake."

Credit: 
Centro Nacional de Investigaciones Oncológicas (CNIO)

A backdoor in mobile phone encryption from the 90s still exists

image: Although the insecure algorithms are still implemented in modern mobile phones, the researchers do not expect them to pose a significant threat to users.

Image: 
RUB, Marquard

The encryption algorithm GEA-1 was implemented in mobile phones in the 1990s to encrypt data connections. Since then, it has been kept secret. Now, a research team from Ruhr-Universität Bochum (RUB), together with colleagues from France and Norway, has analysed the algorithm and has come to the following conclusion: GEA-1 is so easy to break that it must be a deliberately weak encryption that was built in as a backdoor. Although the vulnerability is still present in many modern mobile phones, it no longer poses any significant threat to users, according to the researchers.

Backdoors not useful according to researchers

"Even though intelligence services and ministers of the interior understandably want such backdoors to exist, they are not at all useful," says Professor Gregor Leander, Head of the Workgroup for Symmetric Cryptography. "After all, they are not the only ones who can exploit these vulnerabilities, any other attackers can exploit them as well. Our research shows: once a backdoor is implemented, it is very difficult to remove it." Accordingly, GEA-1 should have disappeared from mobile phones as early as 2013; at least that's what the mobile phone standards say. However, the research team found the algorithm in the current Android and iOS smartphones.

For the study, a team led by Dr. Christof Beierle, Dr. David Rupprecht, Lukas Stennes and Professor Gregor Leander from RUB collaborated with colleagues from Université de Rennes and Université Paris-Saclay as well as the French research institute Centre Inria de Paris and the Norwegian research institute Simula UiB in Bergen. The team will present its findings at the Eurocrypt conference in October 2021. The paper has been available online since 16 June 2021.

The project was embedded in the Bochum Cluster of Excellence CASA - short for Cyber Security in the Age of Large-Scale Adversaries -, which aims at enabling sustainable IT security against large-scale attackers, most importantly national states.

Lottery win more likely than weak code being a coincidence

The IT security experts received the GEA-1 and GEA-2 algorithms from a source who wishes to remain anonymous and verified their authenticity in the first step. The ciphers had been used to encrypt data traffic over the 2G network, for example when sending emails or visiting websites. The researchers analysed how exactly the algorithms work. They showed that GEA-1 generates encryption keys that are subdivided into three parts, two of which are almost identical. Due to their architecture, these keys are relatively easy to guess.

According to the Bochum-based team, the properties that render the cipher so insecure can't have happened by accident. "According to our experimental analysis, having six correct numbers in the German lottery twice in a row is about as likely as having these properties of the key occur by chance," as Christof Beierle illustrates.

GEA-2 algorithm likewise weak - but unintentionally so

The IT experts also scrutinised the GEA-2 algorithm. It is hardly more secure than GEA-1. "GEA-2 was probably an attempt to set up a more secure successor to GEA-1," assumes Gregor Leander. "GEA-2 was hardly better, though. But at least this algorithm doesn't seem to be intentionally insecure."

The encryptions that GEA-1 and GEA-2 produce are so weak that they could be used to decrypt and read live encrypted data sent over 2G. Today, most data traffic is sent over the 4G network, also called LTE. Moreover, the data is now protected with additional transport encryption. Therefore, the researchers assume that the old vulnerabilities that still exist no longer pose a serious threat to users.

Manufacturers don't adhere to standards

Originally, GEA-1 must not be implemented in mobile devices since 2013. "The fact that it is still happening shows that manufacturers are not following the standard properly," explains David Rupprecht. Through the mobile phone association GSMA, the Bochum-based group contacted the manufacturers before publishing their data to give them the opportunity to remove GEA-1 through software updates. In addition, they contacted ETSI, the organisation responsible for telecommunications standards, to also remove GEA-2 from phones. In the future, - so ETSI's decision - smartphones should not support GEA-2 anymore.

Credit: 
Ruhr-University Bochum

Reduced microbial stability linked to soil carbon loss in active layer under alpine permafrost degra

image: Fig. 1 Co-occurrence networks (A) and robustness analysis (B) for microbial communities between lightly (S-SSP) and severely (U-EUP) degraded permafrost.

Image: 
NIEER

Chinese researchers have recently discovered links between reduction in microbial stability and soil carbon loss in the active layer of degraded alpine permafrost on the Qinghai-Tibet Plateau (QTP).

The researchers, headed by Prof. CHEN Shengyun from the Northwest Institute of Eco-Environment and Resources (NIEER) of the Chinese Academy of Sciences (CAS), and XUE Kai from University of Chinese Academy of Sciences, conducted a combined in-depth analysis of soil microbial communities and their co-occurrence networks in the active permafrost layer along an extensive gradient of permafrost degradation.

The QTP encompasses the largest extent of high-altitude mountain permafrost in the world. This permafrost is different than high-latitude permafrost and stores massive soil carbon. An often ignored characteristic of permafrost is that the carbon pool in the active layer soil is more active and directly affected by climate change, compared to deeper layers.

Triggered by climate warming, permafrost degradation may decrease soil carbon stability and induce massive carbon loss, thus leading to positive carbon-climate feedback. However, microbial-mediated mechanisms for carbon loss from the active layer soil in degraded permafrost still remain unclear.

In this study, the researchers found that alpine permafrost degradation reduced the stability of active layer microbial communities as evidenced by increased sensitivity of microbial composition to environmental change, promoted destabilizing network properties and reduced resistance to node or edge attacking of the microbial network.

They discovered that soil organic carbon loss in severely degraded permafrost is associated with increased microbial dissimilarity, thereby potentially contributing to a positive carbon feedback in alpine permafrost on the QTP.

Credit: 
Chinese Academy of Sciences Headquarters

How should governments offer subsidies for clean-energy heating?

Greater Helsinki -- Transitioning to low-carbon energy production is the biggest climate challenge to overcome. Many countries are already looking to adopt clean heating solutions more widely, with the International Energy Agency projecting that by 2045 nearly half of global heating will be done with heat pumps. To ensure speedy uptake, governments are likely to offer subsidies to ensure these energy-efficient options actually make their way into homes and offices.

A new study from Aalto University assesses the impact of heat pumps on energy consumption as well as how heat pumps should be subsidised. These devices run on electricity to warm spaces by efficiently transferring heat from one area to another, cutting buildings' carbon footprints significantly.

'My research shows that a heat pump can reduce carbon dioxide emissions from heating by more than 80 percent. Electrifying heating means we can warm our homes and buildings cleanly. Heat pumps are also truly energy-efficient: they can can produce up to four units of heat for every unit of electricity,' says Jussi Vimpari, a post-doctoral researcher at Aalto University.

In the study, Vimpari compares the prices, rents, heating systems, and emissions from heating, and the percentage of residents' income spent on heating in all residential buildings in eight large Finnish cities, including those in the capital region of Helsinki. In Finland, city buildings are typically heated with oil, district heating, or electricity. Only 15% of heating in the country is currently done with heat pumps.

An average of about 9 percent of household income was spent on heating and installing a heat pump reduced this to roughly 4 percent. The investment required for the pump was an average of €3,800 per resident, unsubsidised, with the cost recouped through lower heating in just over ten years. In Finland, the cost of the unit and its installation is subsidised up to 25-50 percent.

The findings also show that neighbourhoods with lower housing prices are less motivated -- and likely less able -- to invest in heat pumps.

'In areas with high prices, the cost of the heat pump is just a small fraction of the overall cost of the home, around one percent. But in areas where homes are valued at lower prices, the relative cost of the device seems to be too large to invest,' Vimpari explains.

This division in purchase habits means subsidies are going to areas where homeowners are likely to buy the device -- even without the monetary incentive. Vimpari says potential subsidies should be allocated to those who would benefit the most.

'When the cost of the heat pump amounts to a larger percent of the cost of the home, the owner has less motivation and capability to make the investment. This may be especially true because income correlates with housing prices: owners may want to heat their homes more efficiently, but just cannot afford the upfront cost. If governments want to help citizens transition to clean energy, they need to think about those who need the benefits most,' says Vimpari.

Some countries like the United States or Germany still rely mainly on gas boilers for heating, as fuel still costs less than electricity in these markets. The European Union, however, has discussed banning gas boilers in new buildings in efforts to move away from fossil fuels; member nations like Finland promote heat pumps for their energy-efficiency, while neighbouring Sweden spurred sales of the device when they introduced tax on heating oil in the 1990s.

'Eventually all heating has to become non-fussil fuel based. Currently, the electrification of heating with heat pumps looks like the most efficient way to do this, as we have the means to produce emission-free electricity and heat pumps can convert that electricity to heat with very high efficiencies,' Vimpari notes.

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Aalto University

New research finds ways to improve accuracy of Lateral Flow Tests

Research published in the journal ACS Materials and Interfaces has provided new understanding of how false-negative results in Lateral Flow Tests occur and provides opportunity for simple improvements to be made.

Lateral Flow Devices were introduced late in 2020 on a global scale to help detect novel coronavirus infection in individuals, with test results produced rapidly in half an hour or less. However, their potential has been somewhat hindered by inadequate sensitivity, with a high number of false-negative results.

Using X-ray fluorescence imaging from Diamond Light Source, researchers from King's College London set out to identify what could be causing these false-negative results, and what potential modifications could enable increased accuracy.

They identified that the underlying technology of many Lateral Flow Devices is highly accurate and able to theoretically detect trace amounts of the COVID-19 virus, but the limitations fall to the read-out of the device - the technology used to communicate the result of the test.

In the study, they have suggested several potentially simple modifications to the Lateral Flow Devices that could lead to improved performance.

Professor Owen Addison from King's College London said: "Methods to detect infectious individuals who do not show or are yet to show symptoms remain essential for the management of the current pandemic. Lateral Flow Devices are the simplest and most accessible tests available, and our findings show great scope for improving the deficiencies that these tests have been recently criticized for."

The collaboration saw researchers from King's College London, Guy's and St Thomas' Hospital Trust work with Diamond Light Source, a national science facility, where they used light in the form of X-rays that can be up to 100 billion times brighter than the sun to image how the virus interacts with the tests. The project was supported by a rapid award of experimental time at the science facility.

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King's College London

Preformed gel particles tested for enhanced oil recovery

image: Experimental setup of visual fracture-vuggy model

Image: 
Kazan Federal University

A joint paper went out in Journal of Petroleum Science and Engineering.

Petroleum, being a liquid compound, has very good migratory properties, and recovery methods take account of that - using various methods, oilers displace petroleum through cavities and vugs and extract it. However, sometimes oil is "locked" in low-permeability reservoirs, and water displacement used in such cases poses a high risk of reservoir flooding and workplace emergencies.

Many teams work on blocking high-permeability areas in order to make extraction a more controlled and safe process. In particular, there have yet been no efficient agents for reservoirs with high temperatures (up to 140 C) and mineralization (up to 250 grams per liter). Experts from Kazan Federal University, Southwest Petroleum University, Sinopec, and Curtin University joined forces to test novel gel particles in such conditions. The new technique improves on earlier such attempts made by other teams.

Co-author, Senior Research Associate Yuan Chengdong comments, "We'll continue to test our technique on oil deposits in China, where reservoirs with salinity of over 290 grams per liter are quite common. Previous tryouts showed that an increase in recovery can amount to 100 thousand tons. This proves that the reagents are efficient and are very stable under high temperature and high salinity."

Credit: 
Kazan Federal University

How a bath sponge becomes a bio-based industrial filter

image: Prof. Hermann Ehrlich looks at a piece of the new material.

Image: 
TU Bergakademie Freiberg / C. Mokry

Professor Hermann Ehrlich places a piece of sponge in an alkaline, copper-containing ammonia solution that simulates a copper bath from the manufacture of circuit boards for electronic components. About 12 hours later the sponge has turned blue - when dry it is stronger than before, but still very light. "At a pH value of 9 the fibers of the spongin open and the organic compounds of the protein change," explains Prof. Hermann Ehrlich. The copper contained in the ammonia solution reacts immediately with the organic components of the spongin, especially with the amino acid residues, and forms the mineral atacamite. "Like a string, nanometer-sized crystals grow along with the spongin fiber," explains the scientist. They stabilize the framework and at the same time ensure that the sponge is retained in its unique micro-architecture. The team led by Prof. Hermann Ehrlich published the results in a current publication in the journal Advanced Materials.

Can be used as a bio-based filter for wastewater treatment or pollutant removal

The three-dimensional and porous material is inherently a filter. Coupled with the properties of atacamite, there is a wide range of potential for using the new material as an alternative to synthetic filters. "Our team was able to demonstrate experimentally for the first time that the composite material made from marine bath sponges can in principle be used in the development of sensors, catalysts, and antibacterial filter systems," explains co-author Prof. Martin Bertau from the Institute of Chemical Technology at TU Bergakademie Freiberg.

New material can be reused many times over

Does Prof. Hermann Ehrlich put the blue sponge with the crystals in an acidic solution, the reaction runs backwards: the sponge is back in its original state and can be processed again for further applications. "The newly developed material can therefore be recycled again and again," said the Freiberg biomineralogist enthusiastically.

"Even after up to 100 application cycles, the responsiveness of the spongin-atacamite composite is still given," confirms his colleague Prof. Martin Bertau. "If the material is ultimately no longer usable, the sponge is biodegradable and the copper is recovered from the solution - ideally, electrochemically with renewable energies. We have already shown that this is possible," says the chemist.

Background: Biomineralogy and extreme biomimetics at TU Bergakademie Freiberg

For two years now, researchers from Germany, Poland, Australia, Spain, and Ukraine have been developing new biomimetic models and alternatives to plastic scaffolding for modern materials science. They are supported by the German Research Foundation, the Saxon State Ministry for Science, Culture and Tourism and the Alexander von Humboldt Foundation. Extreme Biomimetics is a new scientific field that was established at TU Bergakademie Freiberg in 2013 which deals with the investigation of natural and artificial phenomena for the development of novel bio-inspired 3D composite materials on a centimeter to meter scale.

Credit: 
University of Freiberg / TU Bergakademie Freiberg

Pandemic planning: Government should embrace uncertainty rather than confront it or shy away from it

New research shows the UK's COVID-19 management decisions were based on an outdated pandemic modelling structure and suggests a more resilient approach would have been more effective.

In the initial months of the pandemic, regular updates using graphs showing how the R number was behaving was the mainstay of the Government's strategy for tackling COVID-19.

This type of infection transmission is usually mathematically-based on dividing the population into 'compartments'. Such an approach has been criticised for its limited scope and inability to capture critical factors, such as the effects of testing, contact tracing and isolation. In addition, these existing models tend to look back at what the outcomes were, rather than look forward at future outcomes.

Professor Ashraf Labib, Professor of Operations and Decision Analysis in the Faculty of Business and Law at the University of Portsmouth, is the author of a new paper published this month in the journal of Safety Science. He urges Governments to use a more holistic approach, which provides a much richer modelling and in-depth decision analysis that can lead to better decision making.

Professor Labib has developed a hybrid model - a combination of resilience triangle modelling, which, provides a specific time of 'when' to act and the bowtie modelling that deals with the question of 'how' to act. He then added five guiding principles* which together provide an improved model from which lessons for the future can be learnt.

Professor Labib explains: "Resilience-based modelling with the five proposed principles can enhance public policy decisions. The aim of such modelling is to provide a learning environment on how to absorb failure and provides an opportunity to achieve quick recovery.

"Resilience modelling can offer the answer to 'when' to do things, whereas the bowtie modelling deals with causal analysis and can provide information on the 'how' questions. By combining the two, a balance is achieved in terms of dealing with a disaster, such as the Covid-19 pandemic, at both strategic and operational levels respectively.

"At a strategic level, the phases of prevention of the cause, response and mitigation of the consequences are visualised and strategic milestones can be set accordingly. Whereas, through bowtie modelling more operational details of causal factors and barriers analysis are achieved. Such analysis helps to improve knowledge related to assessing existing barriers and the need for new or improved ones. In addition, the bowtie modelling provides insight to visualise and communicate the complexity of risks in a concise form."

The paper also suggests it is vital that public health simulation exercises are extended to include not just policies related to health, but also include different economic scenarios caused by pandemics.

Professor Labib says: "Given the complex nature of a pandemic and the experiences with COVID-19 in terms of multiple waves, emerging variants and the variety of available vaccines, the main lesson learnt from all of this is to embrace uncertainty rather than to confront it or shy away from it. This is the way we will learn and prepare for future pandemics.

"Resilience as a conceptual idea is profound and considered to have a key role in dealing with disasters such as pandemics. However, there is little research on modelling resilience and integrating it with other approaches in order to systematise its operation. This paper aimed to contribute to this gap through the proposed hybrid enriched model of resilience and bowtie approaches."

Professor Labib urges policy makers to shift the way they approach things. Firstly, a shift in focus of decision making from efficiency to resilience and secondly to embrace the unknown and learn from it.

Credit: 
University of Portsmouth

Research study suggests BAT's Modern Oral products have similar toxicant profile to NRT

Results show BAT's Modern Oral nicotine pouches have a comparable toxicant profile to NRTs, which are currently considered the least risky of all nicotine products*†

The Modern Oral products have far fewer and significantly lower levels of toxicants‡ than cigarette smoke

Data demonstrates how BAT is building A Better Tomorrow™ by providing evidence to show how we are reducing the health impact of our business and delivering Tobacco Harm Reduction

London, 16 June: New research published today indicates that BAT's modern oral (MO) products in the form of tobacco-free nicotine pouches have a toxicant profile that is comparable to nicotine replacement therapies (NRTs) and much lower than traditional oral snus, a category of products that, when used as the sole nicotine product is already established as a reduced risk product compared with cigarettesi,ii.

The study, published in Drug and Chemical Toxicology, analysed four variants of one of BAT's MO nicotine pouch products Lyft+, three snus products, and two different NRT products in a lozenge and a gum format. Each of these products was tested for a range of known harmful and potentially harmful constituents (HPHCs).

The results showed that the MO products had a comparable toxicant profile to NRTs, which are currently considered to be the least risky of all nicotine products. The study also estimated that users of the studied MO products are likely to be exposed to far fewer and significantly lower levels of toxicants than those who use snus.

The findings suggest that MO products, such as Lyft and Velo, should be placed close to NRTs at the lowest exposure end of the nicotine product toxicant delivery continuum.

Dr Aaron Williams, Head of Science, R&D, said; "These results add to the growing body of evidence to support the reduced-risk potential of MO products compared to continuing to smoke.

"They provide important new evidence to support the role of MO products in Tobacco Harm Reduction by demonstrating that they have far fewer and much lower levels of toxicants compared with cigarette smoke and even compared with Swedish-style snus, which is already well established as a reduced risk product when used as the sole nicotine product. This means smokers looking for a alternative nicotine product have another alternative offering greatly reduced exposure to toxicants that comes in an oral format that some may find convenient and easy to use".

BAT is committed to building A Better TomorrowTM by reducing the health impact of its business through providing a range of enjoyable and lower risk products. The company continues to be clear that combustible cigarettes pose serious health risks, and the only way to avoid these risks is not to start or to quit. BAT encourages those who would otherwise continue to smoke, to switch completely to scientifically substantiated, reduced-risk alternatives*.

This study is a part of a comprehensive programme of scientific research designed to assess the reduced-risk potential of non-combustible nicotine products as compared to conventional cigarettes and traditional oral tobacco products.

Study Design

The products in the study were analysed for 24-26 compounds relevant to oral tobacco products, including known harmful and potentially harmful constituents (HPHCs) from the FDA smokeless tobacco reporting list, and the GothiaTek® Standard list of toxicants used to ensure the quality of snus products. Also included were cigarette smoke toxicants (nine smoke constituents prioritised by the WHO's Tobacco Product Regulation Group, 'TobReg9', with the exception of carbon monoxide) not already included in the other lists.

For BAT's MO product, 22 of the 26 compounds tested were below measurable limits, with only moisture, nicotine, formaldehyde and chromium quantified at very low levels. Formaldehyde and chromium were present in some, but not all of the MO variants and only at extremely low levels. From a toxicological perspective, these extremely low levels of formaldehyde (estimated to be 0.004 mg/day for MO users) are unlikely to cause concern, as typical food consumption levels for adults is between 1.5 and 14 mg/day . For the NRT lozenge and gum, 22 and 20 of the 25 compounds were below measurable limits, with the others quantifiable at very low levels. In contrast, only 11 of the 24 compounds tested in the snus product were below measurable limits, whereas 13 compounds were present at quantifiable levels.

To evaluate the toxicant content of MO products in comparison to other tobacco and nicotine products on the risk continuum, we also reviewed the emissions data for 20 HPHCs from published studies of conventional cigarettes, a tobacco heating product (THP) and an e-cigarette. Cigarette smoke contained significant levels of 18 of the 20 measured compounds, THP aerosol contained 12 compounds at quantifiable levels, while e-cigarette vapor contained 7 compounds at quantifiable levels. The MO product had quantifiable levels of only 3 of these 20 HPHCs.

On its own, the toxicant content of a product is insufficient to establish potential health risks to a consumer, so we estimated daily exposure to toxicants for the different products based on average daily consumption of the toxicant. These data indicate that compared with smoking cigarettes, using these MO products would lower daily exposure to 16 of the 18 toxicants, and snus would lower exposure to 10 of the 18 toxicants.

Based on the measured toxicant contents and daily exposure estimates, these data suggest that the studied MO nicotine pouch products would likely fall between snus and NRTs on the toxicant continuum, having substantially lower levels than cigarettes, THPs, snus and vapour products. MO products may therefore provide a lower toxicant-exposure source of nicotine for current smokers who seek a complete substitute for continued smoking. The publication recognised the need for further research to be conducted to further expand the evidence base and the understanding of how MO products may contribute to Tobacco Harm Reduction.

Credit: 
R&D at British American Tobacco

Electrohydraulic arachno-bot a fascinating lightweight

video: A team of researchers of the Robotic Materials Department at the Max Planck Institute for Intelligent Systems and at the University of Boulder in Colorado in the US has found a new way to exploit the principles of spiders' joints to drive articulated robots without any bulky components and connectors, which weigh down the robot and reduce portability and speed. Their slender and lightweight simple structures impress by enabling a robot to jump 10 times its height. At the end of May, the team's work titled "Spider-inspired electrohydraulic actuators for fast, soft-actuated joints" was published in Advanced Science:

https://onlinelibrary.wiley.com/doi/10.1002/advs.202100916
https://doi.org/10.1002/advs.202100916

Image: 
MPI for Intelligent Systems and University of Colorado Boulder

Stuttgart/Boulder - It is not the first time that spiders have served as biological models in the research field of soft robotics. The hydraulic actuation mechanisms they apply to move their limbs when weaving their web or hunting for prey give them powers many roboticists and engineers have drawn inspiration from.

A team of researchers at the Max Planck Institute for Intelligent Systems in Germany and at the University of Colorado Boulder in the US has now found a new way to exploit the principles of spiders' joints to drive articulated robots without any bulky components and connectors, which weigh down the robot and reduce portability and speed. Their slender and lightweight simple structures impress by enabling a robot to jump 10 times its height. At the end of May, the team's work titled "Spider-inspired electrohydraulic actuators for fast, soft-actuated joints" was published in Advanced Science.

The high performance is enabled by Spider-inspired Electrohydraulic Soft-actuated joints--SES joints in short. The joints can be used in many different configurations--not just when creating an arachno-bot. In their paper, the scientists demonstrate a bidirectional joint, a multi-segmented artificial limb, and a three-fingered gripper, which can easily pick up delicate objects. All creations are lightweight, simple in their design, and exhibit high performance making them ideal for robotic systems that need to move rapidly and interact with many different environments.

The researchers developed their SES joints based on the HASEL technology which had previously been invented by the team to build artificial muscles. SES joints mimic a spider-inspired exoskeletal mechanism comprised of both rigid and softer elements, which function similarly to the animal's leg extension through the use of hydraulic forces.

They built a flexible pouch made of thin plastic films (either polyester or polypropylene will do) which they filled with a liquid dielectric--a vegetable-based oil. They then placed electrodes on each side of the pouch. These liquid-filled pockets serve as actuators, in which the hydraulic power is generated through electrostatic forces. The pouch is attached to a rotary joint. When a high voltage is applied between the electrodes, the electrostatic forces cause the liquid dielectric to shift inside the pouch and the joint to flex. SES joints are capable of rotating up to 70 degrees, causing high torques, and can easily restore back to the starting position.

"The SES joints are very simple and light, as there are no peripheral components which weigh down the robot," says Christoph Keplinger, Director of the Robotic Materials Department at the Max Planck Institute for Intelligence Systems. "Many applications for soft robots require versatile actuators. These spider-inspired joints allow for high functionality and consume only little power, they are easy and cheap to make--the plastics we are using are for food packaging--and their production is easily scalable. These are all qualities that are critical for the design of robots, which can move in many different ways and manipulate a variety of objects without breaking them."

A three-fingered gripper was one application for which the team used SES joints to showcase their versatility. If the team had equipped the gripper with a muscle-like structure, it would have been in the way of the object that the gripper is grabbing. Using SES joints as the hinges of the gripper required much less space.

"The research stands out because we can use a wide variety of materials, even the plastic used to make chips bags to create the pouches," the first author of the publication Nicholas Kellaris says. "That way we can implement SES in a wide variety of geometries with specifically tuned actuation characteristics."

"The ultimate goal of our research was not to make a spider robot," Philipp Rothemund, the second author of the publication, adds. "We wanted to develop a state-of-the-art, active joint that you can put in any type of robot."

Especially for small-scale robotic systems of only a few centimeters in size, where the limited space severely restricts the choice of actuator technologies, the SES-joints will come in very useful. For the soft robotics community, this invention is truly a leap forward.

Credit: 
Max Planck Institute for Intelligent Systems

New in Ethics & Human Research, May-June 2021

American Indian and Alaska Native Enrollment in Clinical Studies in the National Institutes of Health's Intramural Research Program
Dejonna Vigil, Ninet Sinaji, and Barbara Karp

This is the first study to provide data about the inclusion of American Indians and Alaska Natives in the National Institutes of Health's Intramural Research Program (NIH-IRP), which provides eligible individuals with access to innovative research treatments that may not otherwise be available. The program's mission is to include all Americans. This study analyzed data from more than 1,800 NIH-IRP protocols active in 2014 and 2017. While the number of American Indian/Alaska Native enrollees increased, it remained at 1% of all participants, a disproportionately low level. The number of clinical studies that enrolled American Indian/Alaska Native individuals also did not change. The authors outline their plans for further research to aid in the ethical inclusion of American Indian and Alaska Native enrollees in clinical research.

Also in the May-June 2021 issue:

"Advance Research Directives: Dementia Researchers' Views on a Prototype Directive and Implementation Strategies," Nola Ries, Elise Mansfield

"Stakeholder Experiences with the Single IRB Review Process and Recommendations for Food and Drug Administration Guidance," Amy Corneli, Carrie B. Domeck, Kevin McKenna, Sara B. Calvert

"SARS-CoV-2 Human Challenge Trials: Rethinking the Recruitment of Health Young Adults First," Kenji Matsui, Yusuke Inoue, Keiichiro Yamamoto

Commentary: "Human Infection Challenge Experiments: Then and Now," Franklin G. Miller, Jonathan D. Moreno

Credit: 
The Hastings Center

Bruisable artificial skin could help prosthetics, robots sense injuries

image: An artificial skin attached to a person's knee develops a purple "bruise" when hit forcefully against a metal cabinet.

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Adapted from <i>ACS Applied Materials & Interfaces</i> <b>2021</b>, DOI: 10.1021/acsami.1c04911

When someone bumps their elbow against a wall, they not only feel pain but also might experience bruising. Robots and prosthetic limbs don't have these warning signs, which could lead to further injury. Now, researchers reporting in ACS Applied Materials & Interfaces have developed an artificial skin that senses force through ionic signals and also changes color from yellow to a bruise-like purple, providing a visual cue that damage has occurred.

Scientists have developed many different types of electronic skins, or e-skins, that can sense stimuli through electron transmission. However, these electrical conductors are not always biocompatible, which could limit their use in some types of prosthetics. In contrast, ionic skins, or I-skins, use ions as charge carriers, similar to human skin. These ionically conductive hydrogels have superior transparency, stretchability and biocompatibility compared with e-skins. Qi Zhang, Shiping Zhu and colleagues wanted to develop an I-skin that, in addition to registering changes in electrical signal with an applied force, could also change color to mimic human bruising.

The researchers made an ionic organohydrogel that contained a molecule, called spiropyran, that changes color from pale yellow to bluish-purple under mechanical stress. In testing, the gel showed changes in color and electrical conductivity when stretched or compressed, and the purple color remained for 2-5 hours before fading back to yellow. Then, the team taped the I-skin to different body parts of volunteers, such as the finger, hand and knee. Bending or stretching caused a change in the electrical signal but not bruising, just like human skin. However, forceful and repeated pressing, hitting and pinching produced a color change. The I-skin, which responds like human skin in terms of electrical and optical signaling, opens up new opportunities for detecting damage in prosthetic devices and robotics, the researchers say.

Credit: 
American Chemical Society

Using microorganisms to monitor water quality within minutes

video: Movement of Paramecium at 1x & 5x permissible limit concentrations of volatile organic compounds (VOCs) water pollutants.

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SUTD

Researchers from the Singapore University of Technology and Design (SUTD) have demonstrated a technology that rapidly detects pollutants in water by measuring their impacts on swimming microorganisms.

Their proof-of-concept, published in Scientific Reports, does not require any chemicals, reagents or laboratory equipment. Instead, it leverages the regular camera of a smartphone as well as microorganisms called Paramecia that are ubiquitous in water bodies--making it especially suitable for assessing water drinkability in underdeveloped regions.

Typically, levels of environmental pollutants are measured by assessing their impact on a given population. Though such impacts may be visible after several days for microorganisms, it takes several years for the true scale to be revealed in larger animals.

To accelerate these measurements, researchers led by Assistant Professor Javier Fernandez at the Fermart Lab used a simple computer vision method to track and measure the impact of pollutants on the behavior of microorganisms. Specifically, they used the changes in the swimming speed of Paramecium aurelia--a single-celled organism can move at surprising speeds of more than ten times their body length per second.

"We chose Paramecia because they are ubiquitous in water bodies and large enough to be seen with a normal camera," explained Fernandez. "They are also fast swimmers, so small differences in their swimming speed will translate to large changes, making them easy to measure."

By tracking the swimming speeds and movements of waterborne Paramecia through a simple microscope set up on camera phones, they found that they could accurately infer the quality of and presence of pollutants in water samples within minutes.

To track the Paramecia, the team recorded videos, then ran an object identification and tracking algorithm that would detect the creatures automatically and calculate their swimming speeds and movement. "Swimming speeds are slightly different between different individuals. But with all this data, we are able to reduce the impact of that variability and obtain general features of their swimming," said Fernandez.

Through their efforts, the researchers showed that the swimming speeds of Paramecia are affected by pollutants like the heavy metals zinc chloride and copper sulfate, as well as the common antibiotic erythromycin. These changes occurred within the range of the pollutants' permissible limits; for instance, at heavy metal concentrations half of those considered unsafe for drinking water, the average swimming speed of Paramecia was nearly halved.

Likewise, there were immediate and significant reductions to the swimming speed of Paramecia at concentrations considered hazardous--potentially allowing researchers to quickly evaluate a specific pollutant's impact in a specific environment.

"Taking a sample of water and measuring the speed of Paramecia can therefore be used as a straightforward method to assess the drinkability of water without the need for specialised equipment or chemicals," said Fernandez. "Usually, you would need a different test for each pollutant, but Paramecia swimming is a global measurement."

The team designed the system under the umbrella of what is known as "frugal engineering," where advanced methods like object tracking and analysis perform tasks with minimal frills, enabling widespread applicability with little resources.

According to the authors, the demonstrated correlation between the swimming speed of microorganisms and pollutant presence, and its assessment in just a few minutes, can be used as a straightforward, resourceless way to assess water quality globally or as a substitute for standardised methods to measure toxicity in laboratory environments.

"In the future, someone might try a different type of microorganism. Various pollutants would affect organisms differently, so pulling data together from multiple microorganisms would enable us to better understand the source of the pollutants," concluded Fernandez. "What we've demonstrated proves that we can get information on water quality in a cheap and simple way, without any technical instruments and in no time at all."

Credit: 
Singapore University of Technology and Design

Intestinal cancers: The 14-3-3sigma gene acts as a tumor suppressor

LMU researchers have identified the 14-3-3sigma gene as an important suppressor of carcinogenesis in the gastrointestinal tract.

Intestinal cancers, also known as colorectal cancer, are among the most prevalent forms of malignancy worldwide. If detected early enough, tumors can be surgically excised. However, as cancer growth progresses, cells may escape from the primary tumor, which can then establish metastatic tumors in other organs. Once such satellite tumors have formed, survival rates fall significantly. Formation of the initial tumor can be triggered by mutations in any of a number of genes. Together with postdocs Markus Winter and Matjaž Rokavec, Professor Heiko Hermeking at LMU's Institute of Pathology has now discovered that a gene called 14-3-3sigma functions as a tumor suppressor in gastrointestinal cancers. Using the mouse as an experimental model, the team demonstrated that inactivation of the 14-3-3sigma gene enhance progression of gastrointestinal cancers and consequently shortens the lifespan of mice.

In earlier work with colon carcinoma cell lines, Hermeking and his colleagues had shown that a protein known as p53, which plays a central role in the suppression of many types of tumors, activates the 14-3-3sigma gene, and that its protein product inhibits passage through the cell cycle. This brake on cell division gives cells more time to repair adventitious or environmentally caused DNA damage, and therefore reduces the risk of uncontrolled cell proliferation. Mutations that inactivate p53 are found in more than half of all tumors. "But it was not clear whether the 14-3-3sigma gene itself plays an important role in the suppression of tumorigenesis in the intestine," says Hermeking.

In a project funded by the German Cancer Research Fund (Deutsche Krebshilfe), his team set out to clarify this issue by analyzing patterns of gene expression in several thousands of tumor samples isolated from patients with colorectal cancer. The data revealed that the expression of 14-3-3sigma is indeed significantly downregulated in these tumors. In addition, this effect was particularly pronounced in metastatic tumors, and the level of expression of the gene showed a negative correlation with the degree of cancer progression. Furthermore, patients with lower levels of expression of the 14-3-3sigma gene were found to have a worse prognosis than those with higher expression - and this finding was independent of whether or not the tumors also contained an inactivating mutation in the p53 gene.

To further explore the significance of 14-3-3sigma in intestinal carcinogenesis, the LMU researchers specifically inactivated the gene in a preclinical mouse model of intestinal cancer. Loss of the gene's function was found to stimulate the formation and growth of tumors in the gastrointestinal tract, and ultimately reduced survival times. Subsequent studies showed that, in the absence of the 14-3-3sigma gene, signaling pathways which are regulated by transcription factors that have been implicated in the formation of metastases are selectively induced. Interestingly, the 14-3-3sigma protein is known to bind and negatively regulate these transcription factors. "Taken together, our results demonstrate that 14-3-3sigma is not only one of the many target genes that are controlled by p53 and mediate its tumor-suppressing function, but also has tumor-suppressive functions on its own in the gastrointestinal tract," says Hermeking.

The authors of the study suggest that detection of decreased expression of the 14-3-3sigma gene in resected primary colon carcinomas could serve as a prognostic indicator in patient populations. "Moreover, the signaling pathways that are triggered upon its inactivation are potential targets for therapeutic interventions," Hermeking adds.

Credit: 
Ludwig-Maximilians-Universität München

What factors put Philippine birds at risk of extinction?

image: A Palawan peacock-pheasant.

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&Ccedil;a?an ?ekercio?lu

The lush forests and more than 7,000 islands of the Philippines hold a rich diversity of life, with 258 bird species who live nowhere but the Philippine archipelago. A new study from University of Utah researchers suggests that, due to deforestation and habitat degradation, more bird species may be endangered that previously thought - including species that may not have been discovered yet. The study is published in Frontiers in Ecology and Evolution.

"Our study provides a roadmap for not only which species may warrant heightened conservation attention," says Kyle Kittelberger, a doctoral student in the University of Utah School of Biological Sciences, "but which traits a species may have that can help inform if it may likely be more at risk of extinction."

Birds of the Philippines

Located in Southeast Asia, the Philippines is considered a global biodiversity hotspot and one of the most biodiverse countries in the world, hosting nearly 600 bird species. A high proportion of the wildlife is endemic to the country, meaning that it is found nowhere else. The Philippines also hosts some of the highest richness of species recently identified as distinct from other closely related species, showing that scientists still have much to learn about the Philippine ecosystems.

Within the last decade the number of endemic species has risen from 172 to 258. This increase of 86 endemic species is more than all the endemic bird species in China (67) or India (75) and more than any country in South America or Africa.

Çağan Şekercioğlu, an associate professor in the School of Biological Sciences who has done ornithological field work in over 90 countries on all continents cannot forget his first visit to the islands.

"When I first visited the Philippines in 2008, I was awestruck by the diversity and especially the endemism of its avifauna but also greatly depressed by the rapid loss of habitat," he says. Excursions into the field took hours due to extensive deforestation. "While looking for rare forest birds in the lowlands of Mindanao, we were literally trying to keep ahead of the loggers that were cutting down century-old rainforest trees within a couple hundred meters of us," he adds. Despite that, in 13 days he saw 161 bird species he had never seen before- and still has 163 bird species to go.

Deforestation, habitat degradation and wildlife exploitation, however, threatens that biodiversity. Southeast Asia, the authors write, is forecast to lose over a third of its biodiversity over the next century. The Philippines in particular ranks 8th in the world for the number of globally threatened bird species.

"There is a pressing need to assess what traits make some species more at risk of extinction than others," Kittelberger says, and use this understanding to help inform conservation efforts."

Traits of threatened birds

To understand the status of Philippine birds, the researchers first determined the bird traits most predictive of extinction risk by correlating bird species' ecological and life history traits, including body mass, diet, elevation range, and clutch size (the number of eggs laid in a nesting season) with their conservation status. A species endemic to the Philippines was significantly more likely to face an extinction risk, they found. Narrow elevation ranges, dependence on forests and high body mass also put birds at risk for extinction.

Then the researchers turned around and evaluated Philippine birds' expected conservation status using those traits, comparing predicted conservation status with the IUCN Red List conservation designations. They found that 84 species were predicted to be in worse shape than their Red List designation, with 14 species predicted to be globally threatened (i.e. vulnerable, endangered, or critically endangered) that aren't currently classified as such.

"We predicted that the Philippine Serpent-eagle and Writhed Hornbill, two species that are not currently recognized as being globally threatened, are respectively endangered and critically endangered," Kittelberger says. "We also predicted that the Palawan Peacock-pheasant, Calayan Rail and Philippine Eagle-owl, three species currently recognized internationally as being vulnerable, are likely endangered species. All these birds therefore warrant heightened conservation attention as they may be more threatened than currently believed."

Lost before they're found 

Among the 84 species predicted to be more threatened, 12 were recently recognized as separate species, and three of those were predicted to be "vulnerable."

"The Philippines have a very high level of endemism and it is currently estimated that there are twice as many bird species in the Philippines that have not yet been split and officially recognized, so there is a real risk of losing species before they are described," Kittelberger says.

Kittelberger says that their research can be applied broadly to assess the conservation status of birds throughout the region.

"The most important thing that the Philippines can do to protect birds," Kittelberger says, "is to address the high levels of deforestation, habitat degradation, and wildlife exploitation, and to increase land protection for wildlife and increase funding for conservation efforts."

Credit: 
University of Utah