Culture

Cargo delivery by polymers

Degradable, bio-based polymers offer options for chemical recycling, and they can be a tool to store and release useful molecules. Scientists have developed a class of sugar-based polymers that are degradable through acid hydrolysis. The researchers also integrated "cargo" molecules in the polymer, which are designed to split off after polymer degradation. Degradable, cargo-bearing polymers are important for medical and sensor applications, says the study published in the journal Angewandte Chemie.

Most plastics resist natural degradation processes. Consequently, increasing contamination of the environment with plastics has led to a call for degradable plastics. Such materials can be subjected to chemical recycling processes, in which chemical reactions break up polymer bonds. Industry then either recovers the monomers and re-subjects them to polymerization, or it collects the resulting small molecules as useful building blocks for further reactions.

However, degradable polymers require a more elaborate polymer design. The linkages between the polymer building blocks should be sensitive to chemical or enzymatic treatments. In addition, sustainable polymers should be made of bio-based feedstock.

Tae-Lim Choi and colleagues from Seoul National University, South Korea, have found a way to produce high-quality polymers from xylose-based monomers. Xylose is a sugar found in plant cell walls. The method they use involves the preparation of the xylose-based monomers, including the attachment of linker groups, and reacting the monomers in a polymerization process called cascade metathesis polymerization.

To test if such plastic materials are degradable, the researchers treated the xylose-based polymers with hydrochloric acid, a treatment commonly found in chemical recycling procedures. The researchers found that the degradability depended on the linkage type. If the polymer contained a linkage made of a carbon atom, the polymer resisted hydrolysis, but linkages made with nitrogen or oxygen atoms led to immediate degradation.

Polymers with a nitrogen-based linkage resulted in compounds called pyrroles, whereas those made with oxygen produced furans. Pyrroles and furans are both abundant, naturally occurring compounds. However, the researchers advise care: "Furan derivatives are known to have a broad range of biological activity, which should be taken into consideration when identifying applications for these polymeric materials," they said.

In block copolymers, different "blocks" of shorter polymer strands are attached to each other. Accordingly, block copolymers have properties arising from those of the single blocks. As many functional materials can be made with block copolymers, the authors tested whether xylose-based block copolymers containing blocks with non-degradable linkages would also disintegrate by acid treatment. They did. "After 24 h, also the carbon-linkage-containing block was almost completely degraded to small molecules, with only a little oligomeric material remaining," the authors reported.

The researchers also integrated small reporter molecules in the polymers. Acid hydrolysis of the polymers with oxygen linkages produced furan derivatives, which subsequently released para-nitrophenol as a reporter molecule. "This type of cargo enables easy quantification of release. However, it can be substituted with other compounds, which exert various functions after their release," Choi says.

Credit: 
Wiley

Research shows preference for male children is declining in Bangladesh

Research from the University of Kent has demonstrated a decline in 'son preference' by women of childbearing age in Bangladesh. However, the study also shows that fertility decisions are still influenced according to son preference.

The paper, 'Is son preference disappearing from Bangladesh?', surveyed a nationally representative sample of Bangladeshi women of childbearing age, born between 1975 and 1994, to assess how son preference is evolving.

The term 'son preference' refers to any situation where parents value sons over daughters and make resulting choices accordingly, which can have a strong economic and demographic impact.

The study finds that among women of childbearing age in Bangladesh, son preference is giving way to a desire for gender balance, a consequence of increased female education and employment. However, in contrast to these stated fertility preferences, actual fertility decisions are still shaped by son preference.

Among those Bangladeshi women yet to have a child, the proportions indicating a desire for sons and daughters were almost identical. For those with one or two children, the presence of a son has a strong negative effect on the desire for additional sons, and the presence of a daughter has a strong negative effect on the desire for additional daughters.

Son preference can have profound economic and demographic consequences upon female adult and maternal mortality, sex-selective abortions, gender differences in breastfeeding, intra-household gender bias in food allocation, gender differentials in infant and child mortality, imbalanced sex ratios and shortages of marriageable women in the population.

The study also found evidence that the desire for gender balance in children was stronger among women who have completed secondary school and those who live in areas with more opportunities for female paid work, specifically in the ready-made garments sector. The desire for gender balance in children is also stronger among women co-residing with their mothers-in-law.

However, survival analysis indicates that actual fertility decisions are still shaped by son preference. The study indicates that those without sons among their first two children are significantly more likely to have another child. The absence of a daughter among the first two children, on the other hand, has no corresponding effect on the decision to have another child.

Dr Zaki Wahhaj, Principle Investigator of the study and Reader in Economics at the University of Kent said: 'Our research reveals a discrepancy between the child sex preferences of women in Bangladesh and their actual fertility behaviour. Whilst son preference has given way to a desire for children of both sexes as far as stated preferences are concerned, we find that actual fertility decisions of women in Bangladesh continue to be shaped by son preference.'

Credit: 
University of Kent

Magnetic waves explain mystery of Sun's outer layer

The Sun's extremely hot outer layer, the corona, has a very different chemical composition from the cooler inner layers, but the reason for this has puzzled scientists for decades.

One explanation is that, in the middle layer (the chromosphere), magnetic waves exert a force that separates the Sun's plasma into different components, so that only the ion particles are transported into the corona, while leaving neutral particles behind (thus leading to a build-up of elements such as iron, silicon and magnesium in the outer atmosphere).

Now, in a new study published in The Astrophysical Journal, researchers combined observations from a telescope in New Mexico, the United States, with satellites located near Earth to identify a link between magnetic waves in the chromosphere and areas of abundant ionised particles in the hot outer atmosphere.

Lead author Dr Deborah Baker (UCL Space & Climate Physics) said: "The different chemical compositions of the Sun's inner and outer layers were first noted more than 50 years ago. This discovery generated what is one of the long-standing open questions in astrophysics.

"The difference in composition is surprising, given that the layers are physically linked, and that matter in the corona originates in the innermost layer, the photosphere.

"Now, thanks to a unique combination of ground-based and space-based observations of the solar atmosphere, carried out nearly simultaneously, it has been possible to definitively detect magnetic waves in the chromosphere and link these to an abundance of elements in the corona that are not found in the inner regions of the Sun.

"Identifying the processes that shape the corona is crucial as we attempt to better understand the solar wind, a stream of charged particles flowing outward from the Sun, which can disrupt and damage satellites and infrastructure on Earth.

"Our new findings will help us to analyse the solar wind and trace it back to where it is coming from in the Sun's atmosphere."

The findings build on those of a related paper by many of the same authors, published last month in the Philosophical Transactions of the Royal Society, which unambiguously detected magnetic waves in the chromosphere, ruling out other factors that could have generated similar magnetic oscillations.

The existence of magnetic waves - vibrations of ions travelling in a certain direction - were first theorised in 1942 and are thought to be generated by the millions of nanoflares, or mini explosions, taking place in the corona each second.

The research team behind the new paper traced the direction of the waves by modelling a range of magnetic fields and found that waves reflecting in the chromosphere seemed to be magnetically linked to areas of abundant ionised particles in the corona.

Dr Marco Stangalini (Italian Space Agency and the National Institute of Astrophysics, Rome), a co-author of both papers, said: "The difference in chemical composition between the inner layer, the photosphere, and the corona is a feature not just of our own Sun, but of stars throughout the Universe. Thus, by observing our local laboratory, the Sun, we can improve understanding of the Universe far beyond it."

The two papers used observations acquired by IBIS, the high resolution spectropolarimetric imager at the Dunn Solar Telescope in New Mexico, together with imaging from the EUV imaging spectrometer (EIS) on the Japan/UK/USA Hinode solar observatory (an instrument designed and built by a UCL-led team) and data from the NASA Solar Dynamics Observatory (SDO).

The researchers say their findings provide a foundation for future research using data from the Solar Orbiter, a European Space Agency-mission acquiring close-up images of the Sun. The mission, which launched last February, includes instruments proposed, designed and built at UCL.

Credit: 
University College London

Patients of Asian and black backgrounds more likely to die from COVID, large study reveals

Patients of Asian and black backgrounds suffered disproportionate rates of premature death from COVID-19, according to a study of 1,737 patients by Queen Mary University of London and Barts Health NHS Trust.

The study, published in BMJ Open, is one of the most comprehensive studies exploring COVID-19 outcomes in black, Asian and minority ethnic populations so far reported, from one of the largest and most diverse UK hospital COVID-19 cohorts, representing a majority ethnically diverse population (only 35.2 per cent of patients identified as White ethnicity).

The work resulted from a new interdisciplinary collaboration between intensive care physicians and HIV physicians. The researchers looked at data from all patients aged 16 years or over with confirmed SARS-CoV-2 infection and admitted to the five acute hospitals within Barts Health NHS Trust, between 1 January and 13 May 2020.

1,737 patients were included in the analysis of whom 511 had died by day 30 (29 per cent).

538 patients (31 per cent) were from Asian, 340 (20 per cent) black and 707 (40 per cent) white backgrounds.

Compared with white patients, those from minority ethnic backgrounds were younger and less frail.

Asian patients were 1.54 times more likely, and black patients 1.8 times more likely, to be admitted to ICU and to receive invasive ventilation, compared to white patients.

After adjustment for age and sex, patients from Asian backgrounds were 1.49 times more likely to die compared to those from white backgrounds, and patients from black backgrounds were 1.30 times more likely to die.

Asian and black patients experienced a 50-80 per cent increased risk of receiving mechanical ventilation in ICU compared with white patients of a similar age.

Dr Yize Wan, Clinical Lecturer at Queen Mary University of London and Specialty Registrar in Intensive Care Medicine & Anaesthesia at Barts Health NHS Trust said: "Our study shows the disproportionate impact of COVID-19 on Black and Asian groups in the first peak. Black and Asian people admitted to Barts Health hospitals with COVID-19 were significantly younger in age, had greater acute disease severity, and higher mortality relative to white patients of the same age and baseline health.

"As the impact of COVID-19 continues to be seen within our community, the importance of responding to the ethnic disparities unmasked during the COVID-19 pandemic is crucial to prevent entrenching and inflicting them on future generations."

Dr Vanessa Apea, Consultant Physician in Sexual Health and HIV at Barts Health NHS Trust and Honorary Senior Lecturer at Queen Mary University of London, added: "Authentic community based participatory research to understand the drivers of these differences, and co-creation of solutions are key to achieving health equity in these communities."

The researchers caution that although the study had a large number of patients, it was not possible to assess a more detailed ethnicity breakdown and it may not reflect the vast heterogeneity within ethnic categories (such as Bangladeshi, Pakistani, black African or black Caribbean).

Separately, two of the research team - Dr Vanessa Apea and Professor Chloe Orkin from Queen Mary and Barts Health - are delivering a new study to understand why Black, Asian and Minority Ethnic communities are so badly affected by the COVID-19 virus and address the lower uptake of the vaccine by people in these groups.

The Amplifying Lives study, funded by Barts Charity, will gain deep insight into the causes of COVID-19 based on the lived experience of East London's racially diverse communities, through interviews and questionnaires. The researchers will work directly with local residents to understand their life before, and during, COVID-19.

Credit: 
Queen Mary University of London

A study explores the alteration of the functional dynamics of the human brain associated with ageing

Normal ageing causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. However, most of the studies have focused primarily on static functional connectivity.

The authors of a recent study published in Cerebral Cortex based their research on the idea that studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes.

The study was led by Gustavo Deco, director of the Center for Brain and Cognition (CBC) and ICREA research professor at the UPF Department of Information and Communication Technologies (DTIC), and Anira Escrichs, a member of his team and first author of the study, who stated: "our research group at UPF, Computational Neuroscience, focuses on investigating the mechanisms underlying brain dynamics and higher brain functions in healthy subjects and also in brain diseases. To this end, we apply computational/theoretical measures of the whole brain in combination with neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and diffusion images (DTI)".

A collaborative project linked to the Aging Imageomics Study

This has been a collaborative effort involving researchers from various medical centres and specialities. Specifically, researchers from the University of Lleida-IRBLleida, experts in metabolomics analysis or the scientific study of chemical processes involving metabolites; from the Dr. Josep Trueta University Hospital of Girona and the Biobank of the Biomedical Research Institute of Girona (IDIGBI), who contributed with the analysis of the microbiota, the cardiovascular resonance images, lifestyle and cognitive level of the study subjects, and participation by the University of Manitoba, Winnipeg (Canada).

To conduct the study, the researchers examined the whole brain of 620 subjects divided into two age groups (middle-aged group from 50 to 64 years versus an older group of 65-91 year-olds), by synchronizing blood-oxygen-level-dependent signals to analyse resting-state fMRI data. "Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability", the study authors assert.

Intrinsic ignition refers to the natural disturbances that occur in a specific area of the brain and have the ability to start the propagation of neuronal activity to other brain regions. Metastability is a concept that helps to understand how brain areas change and transmit information over time. The ability to change, construct or reason with a line of thought is partly possible thanks to this information.

As the authors state: "Our results indicate that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club". These findings suggest that functional whole-brain dynamics are altered in ageing, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

This work is linked to the Aging Imageomics Study, which aims to identify biomarkers of human ageing by analysing biopsychosocial, cardiovascular, metabolomic, and lipidomic and microbiomic images. Using big data techniques to analyse all the data points of the biological phenotype together with health records and measures of lifestyle, the aim of the project is to achieve a deeper understanding of various biological factors (and combinations thereof) underlying people's healthy and unhealthy ageing.

Credit: 
Universitat Pompeu Fabra - Barcelona

Chimpanzee friends fight together to battle rivals

image: Chimpanzees join their close bond partners - related group members and friends - to battle rivals.

Image: 
Liran Samuni, Taï Chimpanzee Project

Chimpanzees, one of the closest relatives of humans, cooperate on a group level - in combative disputes, they even cooperate with group members to whom they are not related. Those involved in fights with neighbouring groups put themselves at risk of serious injury or even death.

Within the context of the Tai Chimpanzee Project researchers observed three chimpanzee communities in Tai National Park in Cote d'Ivoire documenting social relationships, territory range and intergroup encounters amongst others. "We have been able to analyze almost 500 vocal and physical battles from the last 25 years with participation of at least one of the three habituated communities, some of which have caused severe injury or death", says Liran Samuni, the first author of the study.

The study showed that males, as well as females participate in the battles and that three factors increased the likelihood of participation in the intergroup encounter when there were many individuals participating, when maternal kin joined and when non-kin social bond partners were present. "It seems chimpanzees not only consider the sheer number in their sub-group when moving into battle, but they consider the presence of a trusted group member, who will support them in case of an attack", adds Catherine Crockford, senior author of the study. "These results suggest", Liran Samuni continues, "that the link between strong, enduring social relationships and costly collective acts is not uniquely human, but is present in one of our closest living relatives, the chimpanzee."

"This study is part of a series of several investigations linking in-group cooperation with out-group competition", explains Roman Wittig, director of the Tai Chimpanzee Project and senior author of the studies. "We were able to show that out-group competition reduces chimpanzees' reproduction and their territory size. On the other hand, out-group competition increases in-group cohesion and, likely facilitated by the neurohormone oxytocin, reduces the likelihood of defection in battle."

Data from the Tai Chimpanzee Project, with four neighboruing communities observed on a daily basis, will be a key source for scientific investigations into the ultimate and proximate causes of group-level cooperation. "The Tai chimpanzees can teach us", Roman Wittig points out, "what social tools enable human's unique capacity for large-scale cooperation with non-kin".

Credit: 
Max Planck Institute for Evolutionary Anthropology

Highly efficient grid-scale electricity storage at fifth of cost

image: Caption: A Binder-Free Horizontal Electrophoretic Deposition (EPD) Process Is Used to Activate Commercial Carbon Paper Electrodes Using Nitrogen-Doped Graphene

Image: 
WMG, University of Warwick

Researchers in WMG at the University of Warwick, in collaboration with Imperial College London, have found a way to enhance hybrid flow batteries and their commercial use. The new approach can store electricity in these batteries for very long durations for about a fifth the price of current technologies, with minimal location restraints and zero emissions.

The researchers enhanced three hybrid flow cells using nitrogen doped graphene (exposed to nitrogen plasma) in a binder-free electrophoresis technique (EPD).

Wind and solar power are increasingly popular sources for renewable energy. Unfortunately, intermittency issues keep them from connecting widely to the National grid. One potential solution to this problem involves in the deployment of long-duration battery technology, such as the redox flow battery. Despite its great promise the current costs of this system are a key determining factor to real-world adoption. An affordable grid battery should cost £75/kWh, according to the US Department of Energy. Lithium-ion batteries, which lead the charge for grid storage, cost about £130/kWh.

Now WMG researchers have found a way of enhancing hybrid flow batteries or regenerative fuel cell (RFC) technology that could store electricity for very long durations for about one-fifth the cost of current storage technologies, with flexibility in siting and with minimal environmental impact. The technology combines carbon-based electrodes with economically sourced electrolytes, (manganese or sulphur, which are abundant chemicals in the planet) by means of a simple and yet highly effective electrophoretic deposition of nano-carbon additives (nitrogen-doped graphene) that enhance the electrode durability and performance significantly in highly acidic or alkaline environments.

The researchers have published their findings in a paper entitled, 'Hybrid Redox Flow Cells with Enhanced Electrochemical Performance via Binderless and Electrophoretically Deposited Nitrogen-Doped Graphene on Carbon Paper Electrodes' in the December 2020 edition of the journal ACS Applied Materials & Interfaces.

Dr Barun Chakrabarti, a Research Fellow in WMG at the University of Warwick and one of the lead authors on the paper said:

"This EPD technique is not only simple but also improves the efficiencies of three different economical hybrid flow batteries thereby increasing their potential for widespread commercial adoption for grid-scale energy storage."

The hybrid flow battery's total chemical cost is about 1/30th the cost of competing batteries, such as lithium-ion systems. Scaled-up technologies may be used to store electricity from wind or solar power, for multiple days to entire seasons, for about £15 to £20 per kilowatt hour. These batteries are also extremely useful for grid-scale load levelling applications as their design is very flexible due to their unique feature of sizing their power independently of their energy.

The energy density of a hybrid flow battery, especially the polysulphide/air system (S-Air), is 500 times higher than pumped hydroelectric storage. It is also so much more compact and can be placed near any renewable generation.

Credit: 
University of Warwick

Fungi strengthen plants to fend off aphids

GREEN TRANSITION Researchers at the University of Copenhagen have demonstrated that unique fungi strengthen the "immune systems" of wheat and bean plants against aphids. Fungi enter and influence the amount of a plant's own defences, resulting in fewer aphids. The results could serve to reduce agricultural insecticide use and bring Denmark a step further along the path towards its green transition.

Wheat field

Certain fungi are able to establish a close rapport with plants that results in fewer insect infestations and thereby less damage to crops. Until now, it was unclear how these fungi could be used to reduce insect infestations.

"In order for us to really use fungi to control agricultural pests in the future, we need to understand the mechanisms and processes behind their activity. So, it's very exciting that we have managed to advance a step closer", says Associate Professor Nicolai Vitt Meyling of UCPH's Department of Plant and Environmental Sciences.

Fungi strengthen the "immune systems" of crops

The researchers studied three types of fungi to compare their effects against aphid infestations on wheat and bean plants:

"It turned out that two of these fungi were able to effectively reduce aphid infestations by establishing themselves in plant roots and tissues. By combining greenhouse-based experiments with advanced chemical analyses, we can see that the fungi cause plants to increase production of their own natural defences, thus strengthening plant "immune systems". This translates into fewer aphids, which would otherwise weaken a plant", says Nicolai Vitt Meyling, who explains:

"When aphids suck up plant sap, plants lose energy, to the detriment of their root networks and overall growth. However, when fungi-treated plants were attacked by aphids, they were able to compensate by increasing root growth, so that they didn't lose growth potential. Plants left untreated with the fungi couldn't compensate for the attack," says Nicolai Vitt Meyling.

The researchers "treated" wheat and bean plants by applying fungal spores to seed, from which the plants were then germinated and cultivated. They then added a few aphids and observed how many more aphids developed over two weeks in the greenhouse. Thereafter, plant leaves underwent chemical analysis in collaboration with researchers from Aarhus University's Department of Agroecology.

"We see a clear correlation between an increased amount of defence substances in and fewer aphids on the plants treated with two of the fungi. Those plants left untreated with the fungi had lesser amounts of defence substances and more aphids. There is simply a marked upregulation of defence substances in a plant under aphid attack when these specific fungi are present. And, the same treatment produces the same result in both wheat and bean plants," says Nicolai Vitt Meyling.

Thus, the researchers could see that the effect is related to the fungi and not the plant species. The same fungi had the same effect in both the wheat and bean plants, despite the two types of plants not being related and expressing different kinds of defence substances.

Swapping out insecticide for fungi coated seed

The fungi also have an effect on insects that attack the root systems of plants. And, in combination with other environmentally-friendly cultivation methods, could help to reduce insecticide use in agriculture.

"The fungi has the potential to reduce the need for insecticides because treated seeds result in fewer aphids in the field. If we can develop a large-scale method of pre-treating seed with Danish seed producers, to coat plant seeds with these fungi before planting, we may hardly need to spray with insecticides," says Nicolai Vitt Meyling, who concludes:

"Limiting pesticide use is an important aspect of the green transition. This can be an effective and sustainable contribution towards such a reduction."

The next step is to engage in longer term field trials of treated plants. This will allow researchers to gauge the longevity of effects under realistic growing conditions.

The research results have been published in the renowned scientific journal New Phytologist.

Credit: 
University of Copenhagen - Faculty of Science

Addressing the impact of structural racism on disparities in children with Type 1 diabetes

image: Terri H. Lipman, PhD, CRNP, FAAN, the Miriam Stirl Endowed Term Professor of Nutrition, Professor of Nursing of Children, and Assistant Dean for Community Engagement at the University of Pennsylvania School of Nursing

Image: 
Penn Nursing

PHILADELPHIA, PA (January 22, 2021) - Advancements in diabetes technology have improved quality of life and glycemic control in children with type 1 diabetes. However, data show that a subset of children is being left behind. Those from low-income families and non-Hispanic Black (NHB) children are not experiencing benefits associated with technological advances, and are at higher risk for diabetes complications and adverse outcomes through ongoing poor glycemic control.

In an invited commentary to be published in the journal Diabetes Care, researchers describe how socioeconomic disparities and structural racism impact health care for children with diabetes. They illustrate the importance of screening for and addressing social determinants of health and providing community-based interventions. The highest priority is to examine how the diabetes healthcare team is complicit in the process that causes health inequities. They stress the need to align diabetes care with the American Academy of Pediatrics' policy statement that advocates for innovative cross-sector partnerships designed to improve medical, economic, environmental, housing, judicial, and educational equity.

"Aligning diabetes care with this mission is our only hope of eradicating disparities in treatment and outcomes of children with type 1 diabetes," says the article's lead author, Terri H. Lipman, PhD, CRNP, FAAN, the Miriam Stirl Endowed Term Professor of Nutrition, Professor of Nursing of Children, and Assistant Dean for Community Engagement at the University of Pennsylvania School of Nursing.

Credit: 
University of Pennsylvania School of Nursing

New perspectives challenge the idea that saturated fats cause heart disease

In science, sometimes a new perspective can turn our interpretation of the data upside-down, and necessitate a paradigm shift.

There has been, and continues to be, fierce disagreements in nutrition science as to what constitutes a healthy diet. A key controversy is the role of saturated fats in health and disease. Saturated fats are known to increase blood cholesterol levels, and increased blood cholesterol is often observed in people who develop cardiovascular disease.

It has been thought for more than half a century that saturated fats in the diet promote heart disease by increasing blood cholesterol. However, a new model explains why this so-called "diet-heart hypothesis", which has had a major influence on dietary guidelines, may have an alternative explanation.

In a new article published today in the American Journal of Clinical Nutrition, three scientists have raised a question that challenges the diet-heart-hypothesis: Why do saturated fats increase blood cholesterol, and why should this be dangerous? After all, saturated fats occur naturally in a wide variety of foods, including breast milk.

"Cholesterol is a critically important molecule for all cells in the body," explains associate professor Marit Zinöcker, the lead author at Bjørknes University College, Oslo, Norway. "A cell is surrounded by a fluid membrane that controls cell function, and the cells depend on the ability to incorporate a certain amount of cholesterol molecules, so that their membranes don't become too stiff or too fluid."

"The basis of the model is that when saturated fats replace polyunsaturated fats in the diet, less cholesterol is needed in the cell membranes," she explains. The opposite is true when eating more polyunsaturated fatty acids, which include omega-3 and omega-6 fatty acids. "This is because polyunsaturated fats from the diet enter our cell membranes and make them more fluid. The cells adjust the fluidity of their membranes by incorporating cholesterol recruited from the bloodstream. According to the model presented by the researchers, this can explain why blood cholesterol levels decrease when we eat more polyunsaturated fats.

The authors have named the model the "Homeoviscous Adaptation to Dietary Lipids" (HADL) model.

"Cells need to adjust their membrane fluidity according to changes in their environment, such as the access to different types of fat", says co-author Simon N. Dankel, researcher at the Department of Clinical Science, University of Bergen, Norway.

"This phenomenon is called homeoviscous adaptation, and has been described in both microorganisms, vertebrates and in human skin cells. We argue that this is a critical principle in human physiology. Our cells are normally capable of adjusting their cholesterol content according to changes in dietary fats."

"Nutrition research often focuses on what changes in the body, but the question of why something, such as the blood cholesterol, changes, is of equal importance", says co-author Karianne Svendsen, postdoctoral fellow at the Department of Nutrition, University of Oslo, Norway.

This is where the new HADL model comes into play, providing an explanation based on adaptive human physiology. "From the perspective of the HADL model, we find logical explanations for why cells need to change their cholesterol content, and thereby the blood cholesterol, when fats in the diet change," says Zinöcker.

In the paper, other reasons for elevated LDL-cholesterol in people with cardiovascular disease are discussed, such as low-grade inflammation and insulin resistance. This indicates that elevated blood cholesterol caused by metabolic disruptions must be uncoupled from elevated blood cholesterol caused by a major change in intake of dietary saturated fatty acids. It also questions the benefit of lowering blood cholesterol by adding polyunsaturated fatty acids to the diet, and not addressing the root cause.

"There is at best weak evidence that a high intake of saturated fat causes heart disease," says Dankel. "The overall data are inconsistent and unconvincing, not to mention the lack of a logical biological and evolutionary explanation."

"Also, people with metabolic disorders often do not show the expected changes in blood cholesterol when changing their fat intake, suggesting loss of the normal response."

"The research and reasoning that the HADL model is based on indicates that the effect of dietary fats on blood cholesterol is not a pathogenic response, but rather a completely normal and even healthy adaptation to changes in diet." Zinöcker concludes.

The authors state that although the model is based on existing knowledge of cellular mechanisms, the model still needs to be verified. The authors therefore urge researchers to discuss the HADL model using #HADLmodel and to test the model.

Credit: 
The University of Bergen

Proteins unspool DNA so cells can take on unique properties

ITHACA, NY - Biologists have long wondered how complex organisms contain a variety of dramatically different types of cells with specialized functions, even though all of those cells are genetically identical.

New research reveals how proteins, called "pioneer transcription factors," help turn on key genes that give cell types their unique properties and functions.

These pioneer factors, it turns out, help unspool tightly wound coils of DNA so that genetic blueprints in genes can be read and proteins that play roles in biological processes can be made.

The study in fruit flies, "Pioneer-like Factor GAF Cooperates with PBAP (SWI/SNF) and NURF (ISWI) to Regulate Transcription," was published Dec. 10 in the journal Genes & Development.

"We know pretty well what pioneer factors are and what they do, but what we don't know is how they work exactly," said first author Julius Judd, a graduate student in the lab of senior author John Lis, professor of molecular biology and genetics in the College of Agriculture and Life Sciences.

In a cell's nucleus, DNA is bound around a collection of histone proteins called nucleosomes. "DNA is wrapped around it and so the backside of the DNA is inaccessible to recognition because it's up against these proteins," Lis said.

As a result, the transcription factors and machinery required to read DNA sequences for making proteins can't access these genetic codes. Genes therefore exist in a default "off" state until the DNA can be accessed and the codes can be read.

In the study, the researchers focused on a suspected pioneer transcription factor found in fruit flies called GAGA-factor (GAF). Previous work in Lis' lab has shown that GAF binds to target genes and removes nucleosomes; that exposes DNA sequences that mark where transcription of a gene begins, called a promoter sequence.

Research in other labs also suggested that GAF plays a role in embryonic development. And the researchers had evidence that GAF interacts with two different complexes called remodelers, which catalyze the process of removing the nucleosomes from DNA. All of this evidence led Lis, Judd and colleagues to believe that GAF was indeed a pioneer factor.

To test their hypothesis, Judd ran a number of different genome-wide assays to monitor transcription; how accessible the chromatin (spooled DNA) is for transcription; where GAF binds; and the cellular levels of RNA that are translated into protein. They applied these assays both to untreated Drosophila cells and cells where GAF was depleted.

The studies revealed that when GAF binds to a target gene, it recruits a remodeler called PBAP, which removes these nucleosomes and creates an accessible tract of DNA for transcription. Furthermore, at some genes nucleosomes immediately downstream of the promoter also need to be moved. In those cases, GAF relies on a different remodeler, called NURF, to push the first nucleosome along the gene out of the way to make it easier for the transcription machinery to transcribe the DNA.

"We found one pioneer factor that can interact with both remodelers and act at different steps in the process of transcription. That is what is particularly novel," Lis said.

Prior evidence has identified remodeling complexes almost identical to PBAP and NURF in yeast, and there are suggestions that this process occurs in mice and possibly mammals. "We think the way these remodelers are working is a deeply conserved and the conclusions are broadly applicable," Judd said.

Credit: 
Cornell University

Consenting for treatment in advance to reduce leaving the hospital against medical advice among patients with addiction - Experts debate pros and cons

January 22, 2021 - Patients with substance use disorders (SUDs) being treated for serious medical conditions are more likely to leave the hospital against medical advice (AMA) than those without addiction. A special type of contract with healthcare providers might enable patients to consent in advance to life-saving medical care - even if they later refuse treatment, according to a commentary in the Journal of Addiction Medicine, the official journal of the American Society of Addiction Medicine (ASAM). The journal is published in the Lippincott portfolio by Wolters Kluwer.

The Substance Use Advance Directive (SUAD) "has the potential to greatly improve the current state of treatment for life-threatening comorbid conditions in SUD patients through reducing AMA discharges," writes Paul Tobias, MD, JD, MBA, of Ohio Health, Columbus.

But in an accompanying commentary, Kelly K. Dineen, JD, PhD, of Creighton University, Omaha, Neb., cites "obvious practical and ethical challenges" to the SUAD concept, including the lack of any legal basis for overruling patients if they later decide to refuse treatment: "As long as a patient has capacity, they almost always have the final say in consenting to or refusing care."

'Ulysses contracts' for hospitalized patients with SUDs: Consenting to care in advance
Dr. Tobias describes the case of "Jane," a young woman with serious infections related to injection drug use, who was repeatedly hospitalized - but each time, left the hospital without completing treatment. It's a familiar scenario, reflecting the increased rate of AMA discharge among hospitalized patients with SUDs.

Patients always have the right to make decisions about medical treatments, as long as they're not being coerced. However, the "irrationally self-harming decisions" sometimes made by patients with SUDs "[echo] the patterns seen in cases of coercion," according to Dr. Tobias. "By acknowledging SUD as an acting force that is beyond the control of the patient, the reason becomes clear: these patients cannot exercise free choice because their SUD coerces them to make unreasonable decisions."

He proposes SUADs as an option to manage these difficult situations. SUADs are similar to psychiatric advance directives used in patients with psychiatric disorders such as schizophrenia, who know they might lose their decision-making capacity in the future. These specialized instruments are sometimes called "Ulysses contracts" - referring to the story in the Odyssey where Ulysses orders his ship's crew to tie to him to the mast, instructing them not to release him even if he begs them to.

"Ulysses contracts could be applied to patients like Jane by allowing patients who seek treatment of their life-threatening comorbid conditions to choose if and how their physicians can compel them to complete therapy," Dr. Tobias writes. Patients and healthcare providers could follow a shared decision-making approach to determining treatments for SUD and other medical conditions - including the conditions under which patients want to be kept in the hospital without the option of AMA discharge.

In her commentary, Dr. Dineen's key objection to SUADs is that unlike Ulysses contracts used in patients with psychiatric disorders, the proposed SUADs would be applied to people who still have decision-making capacity. She also notes that hospitalized patients with addiction often receive inadequate or no treatment for SUD, including medications for withdrawal symptoms - despite the documented improvement in outcomes - and that this inadequate care is often the cause of AMA discharges. Dr. Dineen also points out the long history of "moralistic, punitive, and discriminatory attitudes and policies," leading to "separate but unequal systems of care" for people with SUDs who are at particular risk for having their autonomy removed.

Dr. Tobias acknowledges the complexities of the SUAD approach. He emphasizes the need for evaluation of state policies "to determine whether the use of SUADs would enable better outcomes with improved patient autonomy and clear physician and nurse responsibilities when patient treatment decisions change."

"Patients with SUD have too long carried the burden of structural and institutional discrimination on the basis of their disease," Dr. Dineen concludes. "Focusing on correcting those is far more just than inflicting more individual harm under the cloak of beneficence."

Richard Saitz MD, MPH, FACP, DFASAM, Editor-in-Chief, Journal of Addiction Medicine, also voices reservations about SUADs: "There are serious concerns with an approach that would override a patient's decision when they have capacity to make it, particularly when that patient (one with addiction) belongs to a class of patients who have been stigmatized, whose autonomy is often taken away, and whose treatment for addiction is often of poor quality."

Credit: 
Wolters Kluwer Health

New blueprint for more stable quantum computers

image: Manuel Grimm is a theoretical physicist at the Paul Scherrer Institute and works on the foundations for building future quantum computers.

Image: 
Paul Scherrer Institute/Markus Fischer

Researchers at the Paul Scherrer Institute PSI have put forward a detailed plan of how faster and better defined quantum bits - qubits - can be created. The central elements are magnetic atoms from the class of so-called rare-earth metals, which would be selectively implanted into the crystal lattice of a material. Each of these atoms represents one qubit. The researchers have demonstrated how these qubits can be activated, entangled, used as memory bits, and read out. They have now published their design concept and supporting calculations in the journal PRX Quantum.

On the way to quantum computers, an initial requirement is to create so-called quantum bits or "qubits": memory bits that can, unlike classical bits, take on not only the binary values of zero and one, but also any arbitrary combination of these states. "With this, an entirely new kind of computation and data processing becomes possible, which for specific applications means an enormous acceleration of computing power," explains PSI researcher Manuel Grimm, first author of a new paper on the topic of qubits.

The authors describe how logical bits and basic computer operations on them can be realised in a magnetic solid: qubits would reside on individual atoms from the class of rare-earth elements, built into the crystal lattice of a host material. On the basis of quantum physics, the authors calculate that the nuclear spin of the rare-earth atoms would be suitable for use as an information carrier, that is, a qubit. They further propose that targeted laser pulses could momentarily transfer the information to the atom's electrons and thus activate the qubits, whereby their information becomes visible to surrounding atoms. Two such activated qubits communicate with each other and thus can be "entangled." Entanglement is a special property of quantum systems of multiple particles or qubits that is essential for quantum computers: The result of measuring one qubit directly depends on the measurement results of other qubits, and vice versa.

Faster means less error-prone

The researchers demonstrate how these qubits can be used to produce logic gates, most notably the "controlled NOT gate" (CNOT gate). Logic gates are the basic building blocks that also classical computers use to perform calculations. If sufficiently many such CNOT gates as well as single-qubit gates are combined, every conceivable computational operation becomes possible. They thus form the basis for quantum computers.

This paper is not the first to propose quantum-based logic gates. "Our method of activating and entangling the qubits, however, has a decisive advantage over previous comparable proposals: It is at least ten times faster," says Grimm. The advantage, though, is not only the speed with which a quantum computer based on this concept could calculate; above all, it addresses the system's susceptibility to errors. "Qubits are not very stable. If the entanglement processes are too slow, there is a greater probability that some of the qubits will lose their information in the meantime," Grimm explains. Ultimately, what the PSI researchers have discovered is a way of making this type of quantum computer not only at least ten times as fast as comparable systems, but also less error-prone by the same factor.

Credit: 
Paul Scherrer Institute

Rediscovery of the 'extinct' Pinatubo volcano mouse

image: The rediscovered volcano mouse, thought to be extinct.

Image: 
(c) Danny Balete, Field Museum

In June 1991, Mount Pinatubo, a volcanic peak on the Philippine Island of Luzon, literally blew its top. It was the second-most powerful volcanic eruption of the 20th century, ten times stronger than Mount Saint Helens, and its effects were devastating. Lava and ash spewed into the surrounding environment in the Zambales Mountains, pooling in layers up to 600 feet thick in the valleys. Following the eruption, powerful typhoons and monsoon rains triggered landslides and ash flows that continued for many months. Eight hundred people lost their lives, and the lush forests that covered the mountain prior to the eruption were destroyed or severely damaged. In recent years, scientists returned to the region to survey the surviving mammal populations, and in a new paper in the Philippine Journal of Science, the team announced the rediscovery of a species of mouse that had long been feared to be extinct.

"When Pinatubo blew up, probably the last thing on anyone's mind was that a little species of mouse was thought to live only on that one mountain, and might well have become extinct as a result. What we've learned subsequently really blew us away", says Larry Heaney, the Negaunee Curator of Mammals at Chicago's Field Museum and one of the paper's authors.

In early 2011 and again in 2012, twenty years after the eruption, Field Museum researcher Danilo (Danny) Balete went to Mt. Pinatubo to study its mammal fauna. Over the course of several months, Balete and his team of field assistants (including local men from the Aeta tribe) surveyed the mammals on the mountain, from the bottom to near the top where the forest had been devastated by the eruption.

"Most of our field work on Luzon and elsewhere in the Philippines has been in natural forested habitats where mammals are most common" says Eric Rickart, Curator of Vertebrates at the Natural History Museum of Utah and lead author on the paper, "but Danny couldn't pass up an opportunity to see how mammals were faring on Mt. Pinatubo."

There were no surveys of the mammals on Mt. Pinatubo prior to the eruption. However, specimens housed in the US National Museum of Natural History provided some records from lower elevations around the mountain. "Most of these early records were for common species of bats collected in the 1950s," says Heaney, "but one specimen was particularly intriguing-a small rodent that became the type specimen, and only example, of a new species described in 1962 as Apomys sacobianus, the Pinatubo volcano mouse."

Conditions on Mt. Pinatubo were very harsh, and the survey work by Balete's team was both grueling and dangerous. Even after 20 years, evidence of the eruption was everywhere. The landscape was very unstable due to the constantly eroding ash and lahar deposits that made working in the steep terrain hazardous. It also greatly slowed the process of plant succession. Vegetation was a sparse mix of native and non-native plants, dense stands of grass (including bamboo), shrubs, low-growing vines, and few trees-all the characteristic of early stage second-growth habitat. It was a far cry from the old-growth tropical forest that covered the mountain before the eruption.

Field surveys of small non-flying mammals elsewhere on Luzon have revealed that old-growth forests contain a great variety of native species and few, if any, non-native "pest" species of rats. But in heavily disturbed second-growth habitats, particularly areas near croplands, the reverse is the case-non-native rats are most abundant, and there are only a few hardy native species. "We thought the work on Pinatubo would confirm this general pattern, so we expected to see few if any of the native species," says Rickart.

A specific motivation for the Pinatubo survey was to discover the fate of Apomys sacobianus, the Pinatubo volcano mouse. "After the eruption of Pinatubo, we looked for this mouse on other peaks in the Zambales Mountains but failed to find it," notes Heaney, "suggesting a very limited geographic distribution for the species. We thought the volcano might be the only place this mouse lived." And based on expectations from islands elsewhere, at the time it seemed possible that the species might have been lost because of the eruption.

However, the survey of Pinatubo produced some very surprising results-a total of 17 species were documented, including eight bats, seven rodents (five native and two non-native species), and even two large mammals (wild pig and deer). Contrary to expectations, non-native rats were not at all common and were restricted to areas near Aeta croplands where such agricultural pests are often most abundant. Despite the fact that all areas surveyed supported sparse, scrubby second-growth vegetation rather than forest, native rodents were abundant everywhere.

Most surprising of all, the most abundant species, overwhelmingly, was the volcano mouse Apomys sacobianus. Far from being wiped out by the eruption, this species was thriving in this greatly disturbed landscape along with other native species that also have a high tolerance for disturbance. "For some time, we've known that many of the small mammals of the Philippines can tolerate habitat disturbance, both natural and human-caused," Rickart says, "but most of them are geographically widespread, not locally endemic species which usually are viewed by conservation biologists as highly vulnerable."

As Mt. Pinatubo recovers from the damage done by the eruption, the forests will return and other species of mammals will move in. "Mt. Pinatubo could be a wonderful place to establish a long-term project to monitor habitat recovery and community re-assembly following the eruption," says Rickart, "such information would be helpful in efforts to regenerate the many areas that have been deforested by people."

After completing the Mt. Pinatubo mammal survey, Danny Balete returned to the Field Museum where he organized specimens and data from the survey, made some early notes for an eventual publication, and then set them aside to finish later. After he suddenly died in 2017 at age 56, Rickart and Heaney say that they picked up and completed the study as a tribute to Balete, who is now recognized as one of the most important figures in Philippine biodiversity science for his extensive research contributions, mentoring of younger colleagues, and promoting enjoyment of nature throughout the Philippines.

"Knowing that a species once thought to be vulnerable, even feared to be extinct, is actually thriving is the finest tribute to Danny that we can imagine," adds Heaney.

Credit: 
Field Museum

Dramatic changes to radiotherapy treatments due to COVID-19

Dramatic changes were seen in the delivery of radiotherapy treatments for cancer during the first wave of the coronavirus pandemic in England.

Much shorter radiotherapy courses were delivered, treatments were delayed where it was safe to do so and some increases were seen in order to compensate for reduced surgical capacity.

Experts believe the changes reflect an impressive adaption of services by the NHS, and that the overall impact on cancer outcomes is likely to be modest.

The new research, led by the University of Leeds, with Public Health England and the Royal College of Radiologists, reveals that there was a decrease in radiotherapy treatment courses of 19.9% in April, 6.2% in May, and 11.6% in June 2020, compared with the same months the previous year.

These decreases equated to more than 3,000 fewer courses of radiotherapy between 23 March and 28 June 2020, than would have been expected*. However, the missed courses were likely to be due to postponement, where the risk of doing so was deemed low. In June though, it appears that the reduced number of courses may reflect a worrying fall in the number of patients being diagnosed with cancer.

The new study is the first to assess the impact of the pandemic on radiotherapy services in England and is published today in The Lancet Oncology.

A rapid change in practice occurred for breast cancer treatments, enabled in part by the results of a UK trial published just as the pandemic struck, which showed a one-week course to be just as effective as a three-week course for many patients**.

Strikingly, the use of the shorter course of treatment went from just 0.2% of all breast cancer radiotherapy courses in April 2019, up to 60.0% of all courses in April 2020.

The switch to shorter courses of treatment was also seen in other types of cancer, and will have helped to keep patients safe and services running during the pandemic.

For some cancer types there was a significant increase in the use of radiotherapy courses compared to the previous year. There was an increase of 143.3% in curative radiotherapy for bladder cancer and 71.3% for oesophageal cancer in May, and 36.3% for bowel cancer in April.

These types of cancer are often treated with surgery. Radiotherapy offers an alternative curative treatment or means to safely delay, and it is likely these timely increases were delivered to keep patients safe when surgery was not possible due to the pandemic.

Radiotherapy guidance during pandemic

Around one in three people with cancer in the UK will receive radiotherapy as part of their treatment***. Radiotherapy can be used to try and cure a patient of their cancer, or to treat pain and other symptoms when curative treatment is not possible.

Treatments are often given using daily targeted doses of radiotherapy over a number of weeks. Every cancer is different, and radiotherapy courses vary depending on the type of cancer and the aim of treatment.

In March and April 2020, national and international recommendations were quickly published to ensure the safe and effective use of radiotherapy, as the first wave of COVID-19 hit the UK. The Royal College of Radiologists helped coordinate the writing and publication of many of these guidelines, with researchers from the University of Leeds contributing to many of these.

Lead author of the new study Dr Katie Spencer, University Academic Clinical Fellow at the University of Leeds and Consultant Clinical Oncologist at Leeds Teaching Hospitals NHS Trust, said: "Radiotherapy is a very important treatment option for cancer, and our study shows that across the English NHS there was a rapid shift in how radiotherapy was used.

"It is impressive to see that the data closely follows the guidelines published at the start of the pandemic. For cancers such as breast and bowel, shorter, more intensive treatments were delivered to provide similar outcomes for patients.

"Where treatment delay is safe, like in prostate cancer, delays were used to reduce the risk of coronavirus exposure. This was particularly important for older patients, who are more vulnerable to the virus.

"In other cases, such as head and neck, and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed."

Treatments during the first wave

The researchers looked at the number of radiotherapy treatments taking place between February and June 2020 within the English NHS, taken from Public Health England's National Radiotherapy Dataset. They compared the number of radiotherapy courses, and their length, with the same time period in 2019, to look at the effects of the coronavirus pandemic and lockdown.

The largest reduction in treatments was seen for patients aged 70 and above (34.4% reduction in April 2020). This likely reflects concern where patient vulnerability to the risks of coronavirus outweighed the low risk expected from delaying treatment in some settings. For example, treatment for prostate cancer fell 77.0% in April 2020 compared to the previous year, and treatments for non-melanoma skin cancer fell 72.4% the same month.

Co-author Dr Tom Roques, Medical Director, Professional Practice for Clinical Oncology at the Royal College of Radiologists, said: "This research shows the incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer, whilst coping with reduced surgical capacity due to the global pandemic.

"Despite the intense pressures on the NHS, it was able to effectively adapt radiotherapy treatments, finding alternative treatment options where possible, and continuing its world-leading standards of patient care.

"In the midst of the current COVID-19 surge, NHS capacity is under even greater stress. However, cancer teams are using all of the clinical experience and innovations from last year to ensure radiotherapy services continue to operate and provide the best care possible for patients."

The research team hope their findings will help healthcare providers to understand the indirect consequences of the pandemic and the role of radiotherapy services in minimising those effects.

This research involved contributions from University of Oxford, Velindre University NHS Trust, Norfolk & Norwich University Hospitals NHS Foundation Trust, and NHS England.

Fewer patients presenting

Dr Spencer, from the University of Leeds' Institute for Health Sciences and the Leeds CRUK Radiotherapy Centre of Excellence, said: "As the country emerged from the first lockdown in June, we saw that the number of patients receiving radiotherapy was still reduced compared to last year.

"The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programmes. This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic and this is likely to have led to the persistent fall in treatments we see. We know that patients who have their cancer diagnosed early have a better chance of being cured so this is really worrying.

"If people have concerns about their health it is really important that they go and seek help. Radiotherapy services remain up and running and are ready to look after people, as always."

Credit: 
University of Leeds