Menopausal hormone therapy not linked to increased risk of developing dementia

Menopausal hormone therapy not linked to increased risk of developing dementia

Use of menopausal hormone therapy (MHT, also known as hormone replacement therapy, HRT) is not associated with an increased risk of developing dementia, regardless of hormone type, dose, or duration, concludes a large UK study published by The BMJ today.

Within the subgroup of women with a specific diagnosis for Alzheimer’s disease, a slight increasing risk association was found with use of oestrogen-progestogen treatments, but measurable only for long-term usage (5 years or more).

The researchers say this study “brings clarity to previously inconsistent findings and should reassure women in need of menopausal hormonal therapy.”

MHT is used to relieve menopausal symptoms such as hot flushes, sleep disturbance, mood swings, memory losses and depression. Treatments include tablets containing oestrogen only, or a combination of oestrogen and progestogen, as well as patches, gels and creams.

Some menopausal symptoms are similar to early signs of dementia. Laboratory studies and small trials have suggested a beneficial link between oestrogen and age related brain decline. However, the largest trial of MHT, the Women’s Health Initiative Memory Study, found an increased risk of developing dementia among users of oestrogen-progestogen treatments.

A recent large observational study in Finland flagged an increased risk of developing Alzheimer’s disease among users of both oestrogen-only and oestrogen-progestogen treatments, but the study had some methodological weaknesses.

To address this uncertainty, researchers at the Universities of Nottingham, Oxford and Southampton set out to investigate the risks of developing dementia for women using any of the menopausal hormone therapy treatments commonly prescribed within the UK National Health Service.

They used two UK primary care databases (QResearch and CPRD) to analyse MHT prescriptions for the 118,501 women aged 55 and older diagnosed with dementia between 1998 and 2020 (cases), and 497,416 women matched by age and general practice, but with no records for dementia (controls).

All information from MHT prescriptions issued more than three years before the case diagnosis was used, including hormone type, dose, and method of administration.

Other relevant factors, such as family history, smoking, alcohol consumption, pre-existing conditions (comorbidities), and other prescribed drugs were taken into account in the analysis.

Overall, 16,291 (14%) cases and 68,726 (14%) controls had been exposed to menopausal hormone therapy in the period up to three years before diagnosis.

After adjusting for the full range of potentially confounding factors, the researchers found no overall associations between use of hormone therapy and risk of dementia, regardless of hormone type, application, dose, or duration of treatment.

Within the subgroup of younger than 80 years who had been taking oestrogen-only therapy for 10 years or more, they found a slightly decreased risk of dementia.

However, an analysis of cases with a specific diagnosis of Alzheimer’s disease showed a slight increase in risk associated with oestrogen-progestogen therapy. This rose gradually with each year of exposure, reaching an average 11% increased risk for use of between 5 and 9 years and an average 19% for use of 10 years or more – equivalent to, respectively, five and seven extra cases per 10,000 woman years.

This is an observational study, so cannot establish cause, and the researchers acknowledge some limitations, such as incomplete recording of menopausal symptoms, particularly for women registered after their menopause, that may have affected their results.

However, the study used a large data sample from primary care records and was designed not only to assess overall risk for women exposed to different types of long term hormone therapy but also to explore the differences between component hormones, offering new, more reliable estimates for doctors and their patients.

The researchers say this study provides the most detailed estimates of risk for individual treatments, and their results are in line with existing concerns in guidelines about long term exposures to combined hormone therapy treatments.

“The findings will be helpful to policy makers, doctors, and patients when making choices about hormone therapy,” they conclude.

Overall, these observations do not change the recommendation that menopausal hormone therapy should not be used to prevent dementia, say US researchers in a linked opinion article. At the same time, it is helpful for providers to put dementia findings in context for patients, they add.

“The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason,” they conclude.



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Extra spacing can boost children’s reading speed

Extra spacing can boost children’s reading speed

New study finds significant benefits for both dyslexic and non-dyslexic children

A new study has found that a child’s reading speed can be improved by simply increasing the space between letters within a piece of text.

The research, led by Dr Steven Stagg of Anglia Ruskin University (ARU), examined the benefits of letter spacing and coloured overlays amongst a group of dyslexic and non-dyslexic children.  It is the first study to investigate how these adaptations can help to reduce specific reading errors.

Published in the journal Research in Developmental Disabilities, the study discovered that text with increased space between each letter provided a benefit to both groups of children. On average, the dyslexia group showed a 13% increase in reading speed, while the comparison group of non-dyslexic children showed a 5% increase in reading speed.

The study involved 59 children aged between 11-15, 32 of whom had a statement of dyslexia, with 27 non-dyslexic children forming a control group. The participants were recruited from six schools in Cambridgeshire, Hertfordshire and London.

Participants read four texts with either standard or extra-large letter spacing, both with and without a coloured overlay. The children were instructed to read the text out loud while being recorded. The recording was used to measure the number of errors they made – specifically missed words, added words, wrong words, and pronunciation – as well as the participants’ reading time.

In addition to improved reading speed for both children with dyslexia and the non-dyslexic group, the larger letter spacing also resulted in a significant reduction in the number of words being missed by the children with dyslexia.  However, the study found that coloured overlays had no significant impact on reading speed or the reduction of errors for either group of children.

Dr Stagg, Senior Lecturer in Psychology at Anglia Ruskin University (ARU), said:

“We found that extra-large letter spacing increases the reading speed of children both with and without dyslexia, and significantly reduces the number of words that dyslexic children skip when reading.

“We believe that extra-large letter spacing works by reducing what is known as the ‘crowding effect’, which can hamper the recognition of letters and reduce reading speed.

“When viewed in the context of previous research, our findings strongly suggest that teaching professionals can be confident that all children would be helped by increased letter spacing in reading materials. As well as being a relatively simple change to make when producing handouts and worksheets, it means that children with dyslexia need not feel singled out by the introduction of specially adapted reading materials, as this is something that everyone can benefit from.

“While we found that colour overlays provided little benefit, we suggest that children should be encouraged to use overlays if they find these help their reading. Colour overlays may not increase reading speeds, but they may extend reading stamina. Previous research suggests their benefits may not become apparent if reading time is less than 10 minutes and the short reading duration of the tests in our study may have put colour overlays at a disadvantage.”



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Genetic risks for depression differ between East Asian and European groups

Genetic risks for depression differ between East Asian and European groups
Specific genes increase the risk of developing depression, according to a new study led by UCL researchers, which also shows that the genes associated with depression vary depending on ancestry group.

The research, published in JAMA Psychiatry, is the largest study into the genetic risks of depression conducted in non-European populations. Using data from East Asian populations, mostly from China, the researchers identified five new gene variants linked to depression but found that the genes linked to depression are different for European and East Asian groups.

For example, people of East Asian descent with higher body mass index are less likely to develop depression, contrary to findings for people of European descent.

Previous studies have identified potential genes involved in depression, but most of these studies looked only at white populations.

The new study provides a better understanding of the underlying biology of depression by identifying differences in the way genes and depression are linked in different populations.

Lead author Professor Karoline Kuchenbäcker (UCL Psychiatry) said: “We were surprised to find many differences in the depression genes for Europeans and East Asians, which shows the need to increase the diversity of samples in these types of studies and to be cautious about generalising findings about genes in causing depression.

“Genetic research has the potential to contribute to new treatments. But if the foundational research did not involve appropriately diverse study populations, then new treatments might not work the same for everyone, and may contribute to health disparities.”

Co-author Professor Cathryn Lewis (King’s College London) said: “While depression is a very common illness, we still understand little about its causes. By identifying the genes involved with depression, we can better investigate the mechanisms of the illness, and it is important to study the genetics of depression in all regions of the world.”

The genome-wide association study, funded by Wellcome and the European Research Council, used genetic data from 194,548 people of East Asian ancestry (15,771 of whom had depression). The study was done in collaboration with the Psychiatric Genomics Consortium, the largest collaborative group of scientists in this field.



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Staying on long-term antidepressants reduces risk of relapse

Staying on long-term antidepressants reduces risk of relapse
When people stop taking antidepressants after a long period of use, just over half (56%) experience a relapse within a year, compared to 39% of those who stay on medication, finds a new study led by UCL researchers.

The researchers say their findings, published in The New England Journal of Medicine, can help doctors and patients to make an informed decision together on whether or not to stop their antidepressants after recovery from a depressive episode.

The study is the first publication from a large discontinuation trial of people taking antidepressants for multiple years in primary care.

Lead author Dr Gemma Lewis (UCL Psychiatry) said: “Prescriptions of antidepressants have increased dramatically over recent decades as people are now staying on antidepressants for much longer. Until now we didn’t know whether antidepressant treatment was still effective when someone has been taking them for many years.

“We have found that remaining on antidepressants long-term does effectively reduce the risk of relapse. However, many people can stop their medication without relapsing, though at present we cannot identify who those people are.”

The National Institute for Health Research-funded study involved 478 primary care patients in England who had been taking long-term antidepressants (citalopram, sertraline, fluoxetine, or mirtazapine) and who felt well enough to consider stopping. 70% had been taking the medication for more than three years.

In a randomised, double-blind controlled trial, half of the study participants stopped taking their medication and half continued. Those who discontinued their antidepressants were given reduced dosages for up to two months as part of a tapering regime, before being given placebo pills only.

Over the following year, 56% of participants who discontinued antidepressants experienced a relapse (a new episode of depression), compared to 39% of participants who kept taking them. Of the 56% who experienced relapse after discontinuation, only half then chose to return to an antidepressant prescribed by their clinician. The researchers say that some relapses, as well as possible withdrawal symptoms, might not have been severe enough for the person to decide they needed to return to their medication.

Those who discontinued their antidepressants were more likely to experience withdrawal symptoms. Despite this, by the end of the study, 59% of the discontinuation group were not taking antidepressants. 

Dr Gemma Lewis said: “Our findings add to evidence that for many patients, long-term treatment is appropriate, but we also found that many people were able to effectively stop taking their medication when it was tapered over two months.

“As 44% of those who discontinued their antidepressants did not relapse after a full year, our findings suggest that some patients might decide to stop their antidepressant, knowing the risk of relapse, but we recommend discussing this with your doctor.”

Senior author Professor Glyn Lewis (UCL Psychiatry) said: “Antidepressants are effective but, like many medications, are not ideal for everyone. In our study, 39% of people who continued on the medication still experienced a relapse, although stopping antidepressants increased the risk of relapse further. There are also other ways to prevent relapse that might help including cognitive behavioural and mindfulness-based therapies.”

Co-lead author Dr Louise Marston (UCL Institute of Epidemiology & Health Care) said: “We do not yet know why some people seem able to come off their antidepressants and some cannot, so further research may help us to predict who can stop antidepressants safely.”

Paul Lanham, lived experience co-researcher, said: “Many patients taking antidepressants long term have absolutely no idea what they would be like without antidepressants. Some will not want to find out, but others will. These results show that staying on antidepressants does reduce the risk of relapse, but it does not guarantee well-being, and some people can stop antidepressants without a relapse.”

The study involved researchers from UCL, the Universities of York, Southampton and Bristol, and McMaster University (Canada).



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Zaki syndrome: Researchers Discover Unknown Childhood Genetic Condition and its Potential Cure

Zaki syndrome: Researchers Discover Unknown Childhood Genetic Condition and its Potential Cure

Describing a previously unknown genetic condition that affects children, researchers at University of California San Diego School of Medicine and Rady Children’s Institute for Genomic Medicine say they also found a potential method to prevent the gene mutation by administering a drug during pregnancy.

The findings publish in the September 30, 2021 issue of The New England Journal of Medicine.

The work involved researchers in Egypt, India, the United Arab Emirates, Brazil and the United States. “Although different doctors were caring for these children, all of the children showed the same symptoms and all had DNA mutations in the same gene,” said senior author Joseph G. Gleeson, MD, Rady Professor of Neuroscience at UC San Diego School of Medicine and director of neuroscience at the Rady Children’s Institute for Genomic Medicine.

The research team dubbed the condition “Zaki syndrome” after co-author Maha S. Zaki, MD, PhD, of the National Research Center in Cairo, Egypt, who first spotted the condition. Zaki syndrome affects prenatal development of several organs of the body, including eyes, brain, hands, kidneys and heart. Children suffer from lifelong disabilities. The condition appears to be rare, but future studies are required to determine prevalence.

“We have been perplexed by children with this condition for many years,” said Gleeson. “We had observed children around the world with DNA mutations in the Wnt-less (WLS) gene, but did not recognize that they all had the same disease until doctors compared clinical notes. We realized we were dealing with a new syndrome that can be recognized by clinicians, and potentially prevented.”

Co-author Bruno Reversade, PhD, a research director at the Agency for Science, Technology and Research (A*STAR) in Singapore, helped identify several families with members suffering from Zaki syndrome and investigate potential therapeutic intervention.

“While we have shown that it’s possible to mimic WNT-deficiency with dedicated drugs, the real challenge was to overcome, and possibly rescue, this congenital disease,” Reversade said.

Using whole genome sequencing, researchers documented mutations in the WLS gene, which controls signaling levels for a hormone-like protein known as Wnt (pronounced wint). Wnt signaling is a highly conserved group of protein pathways involved in embryonic development.

The scientists generated stem cells and mouse models for Zaki syndrome, and treated the condition with a drug called CHIR99021, which boosts Wnt signaling. In each mouse model, they found CHIR99021 boosted Wnt signals, and restored development. Mouse embryos grew body parts that had been missing and organs resumed normal growth.

“The results were very surprising because it was assumed that structural birth defects like Zaki syndrome could not be prevented with a drug,” said first author Guoliang Chai, PhD, a former postdoctoral fellow at UC San Diego School of Medicine now at Capital Medical University in Beijing, China. “We can see this drug, or drugs like it, eventually being used to prevent birth defects, if the babies can be diagnosed early enough.”

Co-authors include: Changuk Chung, Zhen Li, Lu Wang, Trevor Marshall, Nan Jiang, Xiaoxu Yang, Jennifer McEvoy-Venneri, Valentina Stanley, Paula Anzenberg and Nhi Lang, all at Rady Children’s and UC San Diego; Karl Willert, UC San Diego; Emmanuelle Szenker-Ravi, Muznah Khatoo and Vanessa Wazny, Genome Institute of Singapore; Jia Yu and David M. Virshup, National University of Sinapore; Rie Nygaard, Filippo Mancia, Rebecca Hernan and Wendy K. Chung, Columbia University; Rijad Merdzanic and Aida M. Bertoli-Avella, Centogene, Germany; Maria B.P. Toralles and Paula M.L. Pitanga, Laboratorio e Genetica Medica, Brazil; Ratna D. Puri, Sir Ganga Ram Hospital; and Nouriya Al-Sannaa, Dhahran Health Center, Saudi Arabia.

Funding for this research came, in part, from the National Institutes of Health (R01NS048453 and R01NS09800), the Simons Foundation Autism Research Initiative (51486313), the Yale Center for Mendelian Disorders (U54HG006504), the Broad Institute Center for Mendelian Genomics (UM1HG008900), the Center for Inherited Disease Research (N01 268201700006I-0-26800029), the Howard Hughes Medical Institute, the Rady Children’s Institute for Genomic Medicine, a National Medical Research Council Open Fund–Young Individual Research Grant, the National Research Foundation (Singapore), the Branco Weiss Foundation (Switzerland), the European Molecular Biology Organization Young Investigator program, the Strategic Positioning Fund for Genetic Orphan Diseases, and an inaugural A*STAR Investigatorship from the Agency for Science, Technology and Research in Singapore.



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Solving a 50-year-old mystery involving 2 billion-year-old rock

Solving a 50-year-old mystery involving 2 billion-year-old rock

Geologists have been baffled by perforations in an Australian quartzite (rock), identical in shape to burrows made in sands by crustaceans; the original sandy sediment is a billion years older than the oldest known animals. An international team of scientists has now resolved the mystery.

When animals move, they leave traces, such as dinosaur footprints or the burrows of worms. These reveal how ancient animals moved, how they foraged and how they interacted with one another. Trace fossils are as old as the animal world.

Geologists were therefore stunned by the discovery in Western Australia of traces of burrowing animals in ancient quartzite, a rock type that was formed when sandy sediments were subjected to high pressures and temperatures.

“Quartzite is as hard as concrete and impossible for burrowing animals to penetrate,” said Bruce Runnegar, UCLA professor emeritus in the Department of Earth, Planetary, and Space Sciences and co-author of the new research, published today in the journal Proceedings of the National Academy of Sciences. “The traces would therefore have had to be made while the sand was still loose. But the sand was deposited 1.7 billion years ago — a billion years prior to the appearance of the first animals in the fossil record, and its transformation to quartzite occurred more than 1.2 billion years ago, much earlier than the oldest animal fossils, which are less than 0.6 billion years old.”

A Swedish-Australian-Chinese-American team has now offered a solution to this riddle. The scientists present an explanation that does not require unreasonably ancient animals or concrete-chewing worms with diamond teeth.

The team measured the age of sand in the burrows using unusual radioactive minerals.

“The age turned out to be more than a billion years younger than the enclosing quartzite,” said co-author Birger Rasmussen, adjunct professor at the University of Western Australia. “The burrows could therefore have been made by animals.”

But how can animals burrow through hard quartzite? The answer was given by microscopic investigations, which showed that the grains had first separated at contact surfaces, resulting in a friable matrix, and then been fused again through later deposition of quartz, returning the rock to the state of hard quartzite.

“A similar process produced the stuff of the standing stones of Stonehenge,” Runnegar said.

A window in time had thus been opened to enable burrowing, the researchers report. Through comparisons with surrounding sedimentary strata, the scientists could date this window to about 40 million years ago, during the Eocene epoch of Earth’s history.

“Most likely, the traces were made by crustaceans, which invaded southwestern Australia during a short-lived marine transgression associated with the opening of the Southern Ocean,” said senior author Stefan Bengtson, professor emeritus and paleontologist at the Swedish Museum of Natural History.

“These trace fossils in the ‘wrong’ rocks have been a mystery for half-a-century,” Bengtson said. “We are glad to have been able to demonstrate geological processes that resolve this conundrum.”

Story by Stuart Wolpert, UCLA Physical Sciences



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New tool predicts changes that may make COVID variants more infectious

New tool predicts changes that may make COVID variants more infectious

As SARS-CoV-2 continues to evolve, new variants are expected to arise that may have an increased ability to infect their hosts and evade the hosts’ immune systems. The first key step in infection is when the virus’ spike protein binds to the ACE2 receptor on human cells. Researchers at Penn State have created a novel framework that can predict with reasonable accuracy the amino-acid changes in the virus’ spike protein that may improve its binding to human cells and confer increased infectivity to the virus.

The tool could enable the computational surveillance of SARS-CoV-2 and provide advance warning of potentially dangerous variants with an even higher binding affinity potential. This can aid in the early implementation of public health measures to prevent the virus’s spread and perhaps even may inform vaccine booster formulations.

“Emerging variants could potentially be highly contagious in humans and other animals,” said Suresh Kuchipudi, clinical professor of veterinary and biomedical sciences and associate director of the Animal Diagnostic Lab, Penn State. “Therefore, it is critical to proactively assess what amino acid changes may likely increase the infectiousness of the virus. Our framework is a powerful tool for determining the impact of amino acid changes in the SARS-CoV-2 spike protein that affect the ability of the virus to bind to ACE2 receptors in humans and multiple animal species.”

The team used a novel, two-step computational procedure to create a model for predicting which changes in amino acids — molecules linked together to form proteins — may occur in the receptor binding domain (RBD) of SARS-CoV-2’s spike protein that could affect its ability to bind to the ACE2 receptors of human and other animal cells.

According to Kuchipudi, the currently circulating variants include one or more mutations that have led to amino-acid changes in the RBD of the spike protein.

“These amino-acid changes may have conferred fitness advantages and increased infectivity through a variety of mechanisms,” he said. “Increased binding affinity of the RBD of the spike protein with the human ACE2 receptor is one such mechanism.”

Kuchipudi explained that the spike protein binding to the ACE2 receptor is the first and crucial step in viral entry to the cell.

“The binding strength between RBD and ACE2 directly affects infection dynamics and potentially disease progression,” he said. “The ability to reliably predict the effects of virus amino-acid changes in the ability of its RBD to interact more strongly with the ACE2 receptor can help in assessing public health implications and the potential for spillover and adaptation into humans and other animals.”

Costas D. Maranas, Donald B. Broughton Professor in the Department of Chemical Engineering at Penn State, led the development of the team’s new two-step procedure. First, the researchers tested the predictive power of a technique, called Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) analysis, to quantify the binding affinity of the RBD for ACE2. MM-GBSA analysis sums up multiple types of energy contributions associated with the virus’s RBD “sticking” to the human ACE2 receptor. Using data from already existing variants, the team found that this technique was only partially able to predict the binding affinity of SARS-CoV-2’s RBD for ACE2.

Therefore, Maranas and the team explored the use of the energy terms from the MM-GBSA analysis as features in a neural network regression model — a type of deep-learning algorithm — and trained the model using experimentally available data on binding in variants with single amino acid changes. They found that they could predict with more than 80% accuracy whether certain amino acid changes improved or worsened binding affinity for the dataset explored.

“This combined MM-GBSA with a neural network model approach appears to be quite effective at predicting the effect of amino acid changes not used during model training,” said Maranas.

The model also allowed for the prediction of the binding strength of various already observed SARS-CoV-2 amino acid changes seen in the Alpha, Beta, Gamma and Delta variants. This may provide the computational means for predicting such affinities in yet-to-be discovered variants. Nevertheless, even though our computational tool can find amino acid changes that boost binding affinity even further, they have not yet been observed in circulating variants. This may mean that such changes could interfere with other requirements of productive virus infection. It is a reminder that binding with the ACE2 receptor is not the complete story.

The findings published today (Sept. 29) in the journal Proceedings of the National Academy of Sciences.

“Our method sets up a framework for screening for binding affinity changes resulting from unknown single and multiple amino acid changes; therefore, offering a valuable tool to assess currently circulating and prospectively future viral variants in terms of their affinity for ACE2 and greater infectiousness,” said Maranas.

Kuchipudi added, “SARS-CoV-2 can switch hosts as a result of increased contact between the virus and potential new hosts. This tool can help make sense of the enormous virus sequence data generated by genomic surveillance. In particular, it may help determine if the virus can adapt and spread among agricultural animals, thereby informing targeted mitigation measures.”

Co-first authors on the paper are Chen Chen, postdoctoral researcher, and Veda Sheersh Boorla, graduate student in chemical engineering, both at Penn State. Other authors include Deepro Banerjee, graduate research assistant, Penn State; Ratul Chowdhury, postodoctoral associate, Harvard University; Victoria S. Cavener, researcher, Huck Institutes of the Life Sciences, Penn State; Ruth H. Nissly, research technologist in veterinary and biomedical sciences, Penn State; Abhinay Gontu, graduate student in veterinary and biomedical sciences, Penn State; Nina R. Boyle, graduate student in integrative and biomedical physiology, Penn State; Kurt Vandegrift, associate research professor of biology, Penn State; and Meera Surendran Nair, assistant clinical professor of veterinary and biomedical sciences, Penn State.

The United States Department of Agriculture, the United States Department of Energy and the Huck Institutes of the Life Sciences at Penn State supported this research.



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Methane: Potential of an overlooked climate change solution

Methane: Potential of an overlooked climate change solution

Earlier this month, President Biden urged other countries to join the U.S. and European Union in a commitment to slashing methane emissions. Two new Stanford-led studies could help pave the way by laying out a blueprint for coordinating research on methane removal technologies, and modeling how the approach could have an outsized effect on reducing future peak temperatures.

The analyses, published Sept. 27 in Philosophical Transactions of the Royal Society A, reveal that removing about three years-worth of human-caused emissions of the potent greenhouse gas would reduce global surface temperatures by approximately 0.21 degrees Celsius while reducing ozone levels enough to prevent roughly 50,000 premature deaths annually. The findings open the door to direct comparisons with carbon dioxide removal – an approach that has received significantly more research and investment – and could help shape national and international climate policy in the future.

“The time is ripe to invest in methane removal technologies,” said Rob Jackson, lead author on the new research agenda paper and senior author on the modeling study. Jackson is the Michelle and Kevin Douglas Provostial Professor of Energy and Environment in Stanford’s School of Earth, Energy & Environmental Sciences.

The case for methane removal

The relative concentration of methane has grown more than twice as fast as that of carbon dioxide since the beginning of the Industrial Revolution. Removing methane from the atmosphere could reduce temperatures even faster than carbon dioxide removal alone because methane is 81 times more potent in terms of warming the climate over the first 20 years after its release, and about 27 times more potent over a century. Methane removal also improves air quality by decreasing the concentration of tropospheric ozone, exposure to which causes an estimated one million premature deaths annually worldwide due to respiratory illnesses.

Methane: Potential of an overlooked climate change solution 

Graph shows globally averaged, monthly mean atmospheric methane abundance determined from marine surface sites since 1983. (Image credit: NOAA)

Unlike carbon dioxide, the bulk of methane emissions are human-driven. Primary culprits include agricultural sources such as livestock, which emit methane in their breath and manure, and rice fields, which emit methane when flooded. Waste disposal and fossil fuel extraction also contribute substantial emissions. Natural sources of methane, including soil microbes in wetlands, account for the remaining 40 percent of global methane emissions. They further complicate the picture because some of them, such as thawing permafrost, are projected to increase as the planet warms.

While development of methane removal technologies will not be easy, the potential financial rewards are big. If market prices for carbon offsets rise to $100 or more per ton this century, as predicted by most relevant assessment models, each ton of methane removed from the atmosphere could then be worth more than $2,700.

Envisioning methane removal’s impacts

The modeling study uses a new model developed by the United Kingdom’s national weather service (known as the UK Met Office) to examine methane removal’s potential impacts while accounting for its shorter lifetime than carbon dioxide – a key factor because some of the methane removed would have disappeared anyway. The researchers created a set of scenarios by varying either the amount removed or the timing of removal to generalize their results over a wide range of realistic future emissions pathways.

Under a high emissions scenario, the analysis showed that a 40 percent reduction in global methane emissions by 2050 would lead to a temperature reduction of approximately 0.4 degrees Celsius by 2050. Under a low emissions scenario where temperature peaks during the 21st century, methane removal of the same magnitude could reduce the peak temperature by up to 1 degree Celsius.

“This new model allows us to better understand how methane removal alters warming on the global scale and air quality on the human scale,” said modeling study lead author and research agenda coauthor Sam Abernethy, a PhD student in applied physics who works in Jackson’s lab.

From research to development

The path to achieving these climate and air quality improvements remains unclear. To bring it into focus, the research agenda paper compares and contrasts aspects of carbon dioxide and methane removal, describes a range of technologies for methane removal and outlines a framework for coordinating and accelerating its scale-up. The framework would help facilitate more accurate analysis of methane removal factors ranging from location-specific simulations to potential interactions with other climate change mitigation approaches.

Methane is challenging to capture from air because its concentration is so low, but burgeoning technologies – such as a class of crystalline materials called zeolites capable of soaking up the gas – hold the promise of a solution, according to the researchers. They argue for increased research into these technologies’ cost, efficiency, scaling and energy requirements, potential social barriers to deployment, co-benefits and possible negative by-products.

“Carbon dioxide removal has received billions of dollars of investments, with dozens of companies formed,” said Jackson. “We need similar commitments for methane removal.”

Jackson is also a senior fellow at the Stanford Woods Institute for the Environment and the Precourt Institute for Energy and chairman of the Global Carbon Project. Coauthors of the research agenda paper include Josep Canadell of the Global Carbon Project; Matteo Cargnello, an assistant professor of chemical engineering at Stanford, Steven Davis and Chaopeng Hong of the University of California at Irvine; Sarah FĂ©ron, a postdoctoral fellow in Earth system science at Stanford at the time of the research; Sabine Fuss of Humboldt Universität in Germany; Alexander Heyer and Hannah Rhoda, PhD students in chemistry at Stanford; and Edward Solomon, the Monroe E. Spaght Professor of Humanities and Sciences at Stanford and professor of photon science at SLAC National Accelerator Laboratory; Maxwell Pisciotta and Jennifer Wilcox of the University of Pennsylvania; H. Damon Matthews of Concordia University in Montreal; Renaud de Richter of Ecole Nationale SupĂ©rieure de Chimie de Montpellier in France; Kirsten Zickfeld of Simon Fraser University in Canada. Coauthors of both papers include Fiona O’Connor and Chris Jones of the Met Office Hadley Centre.

Both papers were funded by the Stanford Woods Institute for the Environment’s Environmental Venture Projects program, the Gordon and Betty Moore Foundation, the National Sciences and Engineering Research Council of Canada and the Joint UK BEIS/Defra Met Office Hadley Centre Climate Programme. The paper led by Sam Abernethy was also funded by the Stanford Data Science Scholars Program and the European Union’s Horizon 2020 Crescendo Project.

To read all stories about Stanford science, subscribe to the biweekly Stanford Science Digest.

Media Contacts

Rob Jackson, School of Earth, Energy & Environmental Sciences: (650) 497-5841;
rob.jackson@stanford.edujacksonlab.stanford.edu

Sam Abernethy, School of Earth, Energy & Environmental Sciences: (650) 382-9943; sabernet@stanford.edu

Rob Jordan, Stanford Woods Institute for the Environment: (650) 721-1881; rjordan@stanford.edu



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Becoming an exoskeleton expert

Becoming an exoskeleton expert

Exoskeleton devices work, researchers say, for a variety of uses such as speeding up our walking or making running easier. Yet they don’t know what exactly makes exoskeletons effective. What is the benefit of customization, for example? And how much does simply getting used to the exoskeleton matter? Researchers in the Stanford Biomechatronics Laboratory at Stanford University examined these questions and found that training plays a remarkably significant role in how well exoskeletons provide assistance.

“People are amazing at learning new tasks,” said Katherine Poggensee, PhD ’21, a former member of the Stanford Biomechatronics Laboratory. “And so with training alone – just giving people time to learn how to use the device on their own – they can get great benefits from our devices.”

To uncover the secrets of exoskeleton success, Poggensee and Steve Collins, associate professor of mechanical engineering and lead of the Biomechatronics Laboratory, monitored the progress of 15 people outfitted with an ankle exoskeleton emulator – a device that attaches into the shoe and around the shank of a person’s legs and mimics a powered exoskeleton, but allows for abundant customization and fine-tuning through special lab-based controllers.

These people had never used an exoskeleton before, but while they all benefited from training, different approaches yielded vastly different results. Participants who received the most advantageous training conditions expended nearly 40 percent less energy while walking with exoskeleton assistance compared to walking with the exoskeleton turned off. Across all participants, the researchers determined that training contributed about half of the overall benefit offered by the exoskeleton. The research is detailed in a paper published Sept. 29 in Science Robotics.

“The main message for our colleagues is: We need to up our experimental game. We need to really train people,” said Collins, who describes the exoskeleton experience as less like putting on a superhero’s smart armor and more like riding a bike. “Once you learn how to do it well, you can just put on the exoskeletons and start walking and it’s easy – but becoming expert does take a little while.”

Taking the time
The researchers focused on three main questions: Can we train people to use exoskeletons by just giving them a device and having them walk for a long time? Can we help people train faster if we expose them to a variety of exoskeleton behaviors? And, once people are fully trained, how does customized control of the exoskeleton affect performance?

Participants were put into three main groups, each of which experienced five days of training. One group received generic assistance from the exoskeleton emulator (based on what helped participants in the past), another experienced continuous optimization of the device to their specific needs throughout the study, and the third group experienced optimization that was reset each day. As expected, participants in the continuous optimization group saw the greatest drop in energy expenditure and, because they were exposed to some variety in exoskeleton behavior, attained those benefits more quickly.

“What we didn’t expect was how well people did,” said Poggensee.

The people in the most advantageous group – continuous optimization and exposure to moderate variety – were the ones who reduced their energy costs by almost 40 percent. (And many participants did not even perceive how much the exoskeleton was assisting until they returned to walking with it turned off.) By comparing all the tests, the researchers determined that training was responsible for about half this improvement and around one-quarter was due to customization. Poggensee emphasized that customization would likely be even more important for people who have mobility issues.

Another surprise was how long it took participants to become “experts,” which the researchers defined as the point at which their energy improvements plateaued. This took about two hours in the exoskeleton emulators, the equivalent of five miles worth of walking. That may not sound like long, but it is a substantial commitment for lab studies.

“Fortunately for the users of future products, we expect people to accumulate lots of exposure over the course of their first week with a device. So, it shouldn’t inhibit people or prevent people from becoming expert in that context,” said Collins, who is also a faculty affiliate of the Stanford Institute for Human-Centered Artificial Intelligence (HAI), which provided funding for this research. “But, if we really want to understand how people respond to some new device in the lab, we’ll need lengthy protocols.”

Better training
This research points to the value of better understanding training, including how people become accustomed to mobility devices and how training can be improved.

“A big takeaway for me is that we need to let our participants drive our research,” Poggensee said. “We need to give them the time to actually learn how to use the device, so that we don’t interfere with any of the learning.”

The team’s interest was also piqued by the fact that, even after participants qualified as experts, there were still slow improvements to their performance over tens of hours of training. To really get the most out of exoskeletons, researchers may need to study how people’s bodies themselves are adapting; for example, the way muscles strengthen to better take advantage of the device.

For now, Collins and his lab are looking at how to speed up the acquisition of expertise, including a collaboration with Stanford computer scientist Emma Brunskill. And he’s increasingly optimistic about the potential for exoskeletons to become a commonplace device in many peoples’ lives.

“Exoskeletons are coming,” said Collins. “They’re going to improve your life and, once you get used to them, you might not even notice.”

This research was funded by the National Science Foundation and the Stanford Human-Centered Artificial Intelligence Grant Program. Collins is also a member of Stanford Bio-X and the Wu Tsai Neurosciences Institute.

To read all stories about Stanford science, subscribe to the biweekly Stanford Science Digest.

Media Contacts
Taylor Kubota, Stanford News Service: (650) 724-770, tkubota@stanford.edu



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More evidence of how COVID-19 changed Americans’ values, activities

More evidence of how COVID-19 changed Americans’ values, activities

A new UCLA-led study decisively confirms findings of research published earlier this year, which found that American values, attitudes and activities had changed dramatically during the COVID-19 pandemic.

The earlier study, published in February, was based on an analysis of online behavior — Google searches and phrases posted on Twitter, blogs and internet forums. The latest research, published in the open-access journal Current Research in Ecological and Social Psychology, is based on a survey of 2,092 Americans — about half in California and half in Rhode Island.

Patricia Greenfield, a UCLA distinguished professor of psychology and senior author of both studies, said the results indicate that Americans’ activities, values and relationships have begun to resemble those found in small, isolated villages with low life expectancy — such as an isolated Mayan village in Chiapas, Mexico, that she has studied since 1969.

For example, according to the survey, people said that compared with pre-pandemic times, they are now more likely to be growing and preparing their own food, conserving resources, demonstrating less interest in financial wealth and showing greater appreciation for their elders. The researchers found all of those shifts are a function of Americans’ increased focus on survival and their isolation during the pandemic.

The study also found that during the pandemic parents expected their children to help out around the home — for example, by cooking for the family — more than they did before the pandemic.

The fact that the latest findings aligned with those of the earlier research on online trends provides additional support for both studies.

“The replication of findings using two very different methods gives us confidence that our survey findings indicate actual change,” Greenfield said.

In the new paper, the authors write that they expect most people’s behaviors and activities will shift back to pre-2020 norms once the pandemic is more fully under control. But they note that might not be true for people in their 20s and younger, whose values are likely to be more permanently shaped by the events of the past two years.

Californians and Rhode Islanders had lived under stay-at-home orders for a little more than a month in late April and early May 2020, when the study was conducted, and most survey respondents were still self-isolating when they took the survey.

Among the other findings:

  • Respondents reported that, as compared to before the pandemic, they were thinking substantially more during the pandemic about death and dying — including their own mortality and that of their family members, making wills and where they intended to be buried, for example.
  • People said they felt greater appreciation for their family and for elderly people during the pandemic than before.
  • While study participants said they were more focused than before on having enough money to cover basic needs like food and shelter, people were generally less focused on the goal of becoming rich.
  • Respondents reported an increase in the amount of time they spent on activities with other members of the household — shared meals and conversations.

Conducting the study in California and Rhode Island was beneficial because, beyond their differences in size and population, the states offer other useful contrasts: Rhode Island’s population is much less diverse than California’s, and at the time of the survey, Rhode Island’s COVID-19 mortality rate was five times higher than California’s.

The study’s results provide significant new evidence to support Greenfield’s long-held theory of social change, cultural evolution and human development, which was published in 2009 in the journal Developmental Psychology. The theory holds that when people are particularly concerned with their own survival and their social lives narrow to their own households, their activities, values, relationships and parenting expectations tend to shift to resemble those typical of small rural communities with low life expectancy. (When Greenfield began studying the Mayan village in Mexico, for example, approximately 35% of children there died before age 4.)

Greenfield said the theory was borne out during 2020 and 2021, even as the COVID-19 pandemic added two new elements — increased mortality and stay-at-home mandates — to the conditions she had previously taken into account.

“The experience of respondents in both states confirmed all of the predicted shifts,” Greenfield said. “The basic human responses to survival threat and limited contact with strangers have been conserved throughout human history and cultural evolution. This suggests that such reactions could be universal human responses that will be similar everywhere in response to the pandemic.”

To evaluate that idea, the researchers are now testing whether the findings from their U.S. studies also hold true in four other nations: Indonesia, Japan, Mexico and Turkey.

The study’s co-authors are Genavee Brown, a psychology lecturer at Northumbria University in England, and Han Du, a UCLA assistant professor of psychology. The research is being published as part of a journal special issue on the ecological and social psychology of the pandemic.



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Does an ally against climate change lie beneath our feet?

Does an ally against climate change lie beneath our feet?

By enhancing soil’s ability to store carbon, the ground we walk on could play an essential role in keeping carbon dioxide out of the air.

If we’re going to fight the effects of climate change, we’re going to have to get our hands dirty.

‘With a huge potential to act as a carbon sink, the soil that sits right under our feet could be at the front lines of climate change,’ said Dr Dragutin Protic, CEO of GILab, a company dedicated to developing solutions based on ICT and geoinformatics.

A carbon sink is a reservoir capable of accumulating and storing carbon for an indefinite period. In doing so, it lowers the concentration of carbon dioxide (CO2) from the atmosphere.

According to Dr Protic, who cited some recent scientific research, soil has the potential to remove an estimated 1.09 gigatonnes of CO2 per year.

From carbon sink to carbon emitter

Even though soil carbon sequestration appears to be a natural, no-regret solution to mitigating climate change, after decades of poor land management, Europe’s soils have been significantly degraded. ‘Soil degradation leads to a reduction in soil organic matter (SOM), which is where carbon is stored,’ explained Dr Protic. ‘In fact, according to recently published scientific research, nearly half of EU soils now have less than 2% SOM.’

As a result, instead of capturing carbon, soil is releasing carbon into the air, setting the scene for a climate catastrophe.

‘Europe’s croplands are losing carbon at a rate of 0.5% per year,’ warned Jean-Francois Soussana, a researcher and vice-chair at INRAE, (France’s National Research Institute for Agriculture, Food and Environment), and a member of the Mission Board on Soil Health and Food. ‘The picture is even more dire for peatlands which, as they are being rapidly drained, release huge amounts of carbon into the atmosphere.’

In an effort to reverse this trend, both Dr Protic and Soussana are leading efforts to preserve and enhance soil’s carbon sequestration capabilities. ‘Increasing carbon sequestration in soil enhances its resilience to the rapidly changing climate,’ said Soussana. ‘It also improves the quality and fertility of agricultural soils, as well as contributing to food security.’

Empowering soil sequestration smart farmers

As both researchers point out, storing carbon in soil organic matter requires healthy plants, high-quality soils and, most importantly, smart farmers. ‘It seems crucial to empower farmers and other stakeholders through effective knowledge creation and sharing,’ remarked Soussana.

One initiative helping to facilitate this knowledge exchange is the AgriCapture project. Led by Dr Protic, the project is developing a platform that uses Earth Observation to help farmers and public authorities explore opportunities in regenerative agriculture – a method of producing food that has a positive impact on the environment.

Earth Observation uses remote sensing technologies, such as the EU’s Copernicus satellite system, along with various ground-based techniques, to gather information about the Earth’s physical, chemical and biological systems. Using this data, the platform will map soil carbon and monitor soil carbon sequestration across Europe.

‘This will allow farmers to visually see how implementing regenerative agriculture practices could increase both carbon sequestration and farm profitability,’ explained Dr Protic. ‘It will also allow farmers to monitor their carbon release/capture ratio to ensure that all carbon offsetting goals are being met.’

The AgriCapture project is also working to verify and support the implementation of regenerative agricultural practices that, if successful, would result in the certification and generation of ‘carbon credits’.

‘Considering soil’s significant potential to act as a carbon sink, regenerative agriculture is a powerful tool for mitigating climate change,’ said Dr Protic.

Putting farmers at the vanguard of carbon sequestration

Another initiative using data to drive soil carbon sequestration is CIRCASA. Led by INRAE, the initiative is working to build an integrated soil carbon balance monitoring system and foster international research cooperation on soil carbon.

According to Dr Soussana, who leads the initiative, by bringing together data from satellites, soil surveys, long-term experiments and CO2 flux measurements, the system will empower farmers to be at the vanguard of soil carbon sequestration.

Beyond simply enabling farmers to monitor soil organic carbon, Soussana says the system can help teach us to create healthy soil by supporting nature-based carbon sequestration. ‘By ensuring that farmers know exactly how much carbon is being stored in their soil, they will be well positioned to make informed decisions that will lead to both healthy yields and a healthy planet,’ said Dr Soussana.

Rehabilitating the carbon sink

Through initiatives like AgriCapture and CIRCASA, Dr Soussana is confident that Europe will be able to enhance its soils’ carbon sequestration levels, thus ensuring that soil remains a carbon sink and not a carbon emitter.

‘We really do not have a choice, and we have to act now,’ stated Soussana. ‘Without carbon sequestration and the conservation of soils, I don’t see a viable route to staying within the +2°C by 2030 as proposed by the Paris Climate Agreement or to achieving the ambitious goals of the European Green Deal.’

Laying the foundation for a common EU framework to preserve, protect and restore soil, the Commission is adopting a new Soil Strategy this year. In addition, a Horizon Europe mission will lead the transition towards healthy soils for people, nature and the climate by 2030.

This article is part of our Monthly Focus titled Bringing Europe’s soils back to life. The research in this article was funded by the EU. If you liked this article, please consider sharing it on social media.



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Faces of ancient mummies revealed via DNA

Faces of ancient mummies revealed via DNA

At the 32nd International Symposium on Human Identification (ISHI), being held this week in Orlando, FL, Parabon NanoLabs will unveil for the first time the predicted faces of three ancient mummies from an ancient Nile community in Egypt known as the Abusir el-Meleq. The mummy samples, estimated to be between 2,023 and 2,797 years old, were processed by researchers from the Max Planck Institute for the Science of Human History and the University of Tubingen in Germany (Schuenemann et al. 2017).1 Enzymatic damage repair was performed on each sample, after which they were sequenced with a capture assay targeting 1.24 million single nucleotide polymorphisms (SNPs) and aligned to the human reference genome. Parabon used the resulting whole-genome sequencing data, which is publicly available in the European Nucleotide Archive (ENA), and selected three samples with the highest quality data to analyze. The company believes this is the first time comprehensive DNA phenotyping has been performed on human DNA of this age, and the results are being presented to the forensic community in ISHI poster #51.Learn More About Snapshot DNA Analysis »

This work was made possible by recent bioinformatic advances in the field of low-coverage imputation, which allows for highly accurate determination of common SNP genotypes from low-coverage sequencing data. The sequencing coverages for the three mummy samples were only 0.13X, 0.23X, and 0.96X, respectively, meaning that each position in the genome was covered less than one time on average. Because individuals have two copies of each SNP, only 0.1%, 0.3%, and 2.8% of the SNPs, respectively, could be directly called from the data, which would not be enough information for phenotype prediction or for traditional imputation. With low-coverage imputation, however, the SNP call rates jumped to 29%, 39%, and 65%, respectively. Parabon bioinformaticist and WGS analyst, Dr. Janet Cady, who spearheaded the work, is enthusiastic about the results. “Parabon has been the leader in forensic microarray analysis for years, and with the introduction of this new imputation technology, we can now handle even the most challenging samples, ancient or forensic” she said.See All Published Police Investigations »

After the imputation step, Parabon applied its Snapshot DNA Phenotyping pipeline to each of the three mummy samples. Snapshot was designed to operate on challenging forensic samples, so it is specifically calibrated to handle missing data, some of which remains even after low-coverage imputation. Snapshot predicted each mummy’s ancestry, pigmentation, and face morphology. Interestingly, their ancestry was determined to be more similar to modern Mediterranean and Middle Eastern individuals than to modern Egyptians. Their complexions were predicted to be light brown, with dark eyes and hair and no freckles. These results are highly consistent with Schuenemann et al’s conclusions that “ancient Egyptians shared more ancestry with Near Easterners than present-day Egyptians, who received additional sub-Saharan admixture in more recent times” and that they had an allele for lighter skin. Three-dimensional face morphology was inferred by predicting the values of face principal components (PCs), which were then transformed into 3D graphical meshes. The face predictions were compared to one another, and heat maps were calculated to show the differences between the subjects. These differences were then emphasized to create caricatured faces, which were combined with the pigmentation predictions to create composites of the individuals’ likely appearance at age 25 by Parabon’s forensic artist.Read More Snapshot Success Stories »

“It’s great to see how genome sequencing and advanced bioinformatics can be applied to ancient DNA samples,” said Dr. Ellen Greytak, Parabon’s Director of Bioinformatics. “Just like in Parabon’s law enforcement casework, these techniques are revolutionizing ancient DNA analysis because they operate on fragmented DNA and have been shown to be sensitive down to only 10 picograms of DNA.”

A print-ready PDF of the scientific poster can be downloaded from Parabon’s website at https://snapshot.parabon.com/ishi2021-posterFaces of ancient mummies revealed via DNA.



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Wiggling worms suggest link between vitamin B12 and Alzheimer’s

Wiggling worms suggest link between vitamin B12 and Alzheimer's

Worms don’t wiggle when they have Alzheimer’s disease. Yet something helped worms with the disease hold onto their wiggle in Professor Jessica Tanis’s lab at the University of Delaware.

In solving the mystery, Tanis and her team have yielded new clues into the potential impact of diet on Alzheimer’s, the dreaded degenerative brain disease afflicting more than 6 million Americans.

A few years ago, Tanis and her team began investigating factors affecting the onset and progression of Alzheimer’s disease. They were doing genetic research with C. elegans, a tiny soil-dwelling worm that is the subject of numerous studies.

Expression of amyloid beta, a toxic protein implicated in Alzheimer’s disease, paralyzes worms within 36 hours after they reach adulthood. While the worms in one petri dish in Tanis’s lab were rendered completely immobile, the worms of the same age in the adjacent petri dish still had their wiggle, documented as “body bends,” by the scientists.

“It was an observation my master’s student Kirsten Kervin made,” said Tanis, an assistant professor in UD’s Department of Biological Sciences. “She repeated the experiment again and again, with the same results.”

After years of research, the team finally turned up an important difference, Tanis said. While all the worms were grown on a diet of E. coli, it turns out that one strain of E. coli had higher levels of vitamin B12 than the other. Although Tanis’s work was focused on genetic factors at the time, she redirected her research to examine this vitamin and its protective role.

Learning from worms

C. elegans is a nematode, a slender, transparent worm only about a millimeter long, that lives in soil, where it eats bacteria. Since the 1970s, this worm has been viewed as a model organism, the subject of numerous studies because it is a much simpler system than us humans for studying cell biology and diseases.

“As humans, we have immense genetic diversity and such complex diets that it makes it really hard to decipher how one dietary factor is affecting the onset and progression of Alzheimer’s,” Tanis said. “That’s where the worms are amazing. The worms we use all have exactly the same genetic background, they react to amyloid beta like humans do, and we can exactly control what they eat, so we can really get down to the molecular mechanisms at work.”

In the brains of humans with Alzheimer’s, the buildup of amyloid beta over the years causes toxic effects in cells, resulting in reduced energy, fragmentation of the mitochondria — the cells’ power plants, and oxidative stress from an excess of free radicals. The same thing happens in C. elegans, Tanis said, but in a matter of hours. Amyloid beta causes paralysis in the worms.

“The read-out is black or white — the worms are either moving or they are not,” Tanis said. “When we gave vitamin B12 to the worms that were vitamin B12 deficient, paralysis occurred much more slowly, which immediately told us that B12 was beneficial. The worms with B12 also had higher energy levels and lower oxidative stress in their cells.”

The team determined that vitamin B12 relies on a specific enzyme called methionine synthase to work. Without the presence of that enzyme, B12 has no effect, Tanis said. Also, adding the vitamin to the diet only worked if the animals were deficient in B12. Giving more B12 to animals with healthy levels does not help them in any way. The team also showed that vitamin B12 had no effect on amyloid beta levels in the worms.

Tanis team power

Tanis credits her students for their hard work and contributions. The first author on the research article, Andy Lam, is pursuing a dual degree at UD — a doctorate in biological sciences and a master of business administration. He spent years working on the laboratory protocols critical to the study. He ran dozens and dozens of experiments and documented observations overnight numerous times.

A future goal is to automate these experiments using a high-throughput system at UD’s Bio-Imaging Center coupled with deep learning analysis to detect if the worms are moving or not. That would allow the team to more rapidly examine the interactions between diet and genetics.

“We’ve essentially identified this molecular pathway and we’re looking to see what else it activates,” Tanis said. “Can B12 be protective for multiple neurodegenerative diseases such as ALS and Parkinson’s? We’re looking into it.”

While Kirsten Kervin graduated from UD with her master’s degree and is now a research scientist at WuXi AppTec in Philadelphia, it was her astute observation about C. elegans that set the project into motion.

“That initial observation opened up an entirely different world,” Tanis said, “which is somehow the story of my research career here at UD. I came here thinking I would be studying one thing, but now I’m studying another. So it hasn’t been straightforward, but it has opened up an entirely new research area we are pursuing.”

That “we” working on this project now includes two graduate students, a postdoctoral research associate, three undergraduate students and collaborations with the Bio-Imaging Center and multiple UD labs.

“Right now, there is no effective treatment for Alzheimer’s disease,” Tanis said. “There are certain factors that you cannot change – you cannot change the fact that you age, and you cannot change a genetic predisposition to Alzheimer’s disease. But one thing you can control is what you eat. If people could change their diet to affect the onset of disease, that would be fantastic. That’s something my lab is excited to continue to explore.”



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Stress of COVID-19 pandemic caused irregular menstrual cycles

Stress of COVID-19 pandemic caused irregular menstrual cycles

Women who menstruate experienced irregularities in their menstrual cycle because of increased stress during the COVID-19 pandemic, a new Northwestern Medicine study has found.

This is the first U.S. study to evaluate the impact of stress on peoples’ periods.

The study surveyed more than 200 women and people who menstruate in the United States between July and August 2020 in order to better understand how stress during the COVID-19 pandemic influenced their menstrual cycles. More than half (54%) of the individuals in the study experienced changes in their menstrual cycle following the start of the COVID-19 pandemic in March 2020.

Individuals who experienced higher levels of stress during the COVID-19 pandemic were more likely to experience heavier menstrual bleeding and a longer duration of their period, compared to individuals with moderate stress levels, the study found.

The study, “Impact of Stress on Menstrual Cyclicity During the COVID-19 Pandemic: A Survey Study,” was published September 28 in the Journal of Women’s Health. It provides a better understanding of how the COVID-19 pandemic has impacted women’s mental and reproductive health, the study authors said.

“We know added stress can negatively impact our overall health and well-being, but for women and people who menstruate, stress can also disrupt normal menstrual cycle patterns and overall reproductive health,” said lead and corresponding author Nicole Woitowich, research assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine.

Prior research has found that menstrual cycle irregularities are often reported by women who experience mood disorders such as anxiety and depression, or by those who are facing acute life stressors such as natural disasters, displacement, famine or defection.

“Given the unprecedented nature of the pandemic and its significant impact on mental health, this data is unsurprising and confirms many anecdotal reports in the popular press and on social media,” Woitowich said.

Since the onset of the pandemic, social media has been one of the major platforms where women and people who menstruate could share questions or concerns about their menstrual cycles. Only recently have these concerns been addressed by the biomedical research community.

“Reproductive health should not be ignored in the context of COVID-19,” Woitowich said. “We are already seeing the ripple effects of what happens when we fail to consider this important facet of women’s health as many are now experiencing menstrual cycle irregularities as a result of the COVID-19 vaccines or COVID-19 infection.”



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Clover growth in Mars-like soils boosted by bacterial symbiosis

Clover growth in Mars-like soils boosted by bacterial symbiosis

Clover plants grown in Mars-like soils experience significantly more growth when inoculated with symbiotic nitrogen-fixing bacteria than when left uninoculated. Franklin Harris of Colorado State University, U.S., and colleagues present these findings in the open-access journal PLOS ONE on September 29, 2021.

As Earth’s population grows, researchers are studying the possibility of farming Martian soils, or “regolith.” However, regolith is lacking in some essential plant nutrients, including certain nitrogen-containing molecules that plants require to live. Therefore, agriculture on Mars will require strategies to increase the amount of these nitrogen compounds in regolith.

Harris and colleagues hypothesize that bacteria could play a cost-effective role in making Martian soils more fertile. On Earth, bacteria in soils help convert or “fix” atmospheric nitrogen into the molecules that plants need. Some of these microbes have symbiotic relationships with plants, in which they fix nitrogen within nodules found on plant roots.

To explore a possible role for symbiotic nitrogen-fixing bacteria in astroagriculture, the researchers grew clover in man-made regolith that closely matches that of Mars. They inoculated some of the plants with the microbe Sinorhizobium meliloti, which is commonly found in clover root nodules on Earth. Previous research had shown that clover can be grown in regolith, but had not explored inoculation with nitrogen- fixers.

The researchers found that the inoculated clover experienced 75% more root and shoot growth compared to the uninoculated clover. However, the regolith surrounding the inoculated plants showed no signs of elevated NH4—an essential nitrogen-containing molecule for plants—compared to the regolith surrounding uninoculated plants.

These findings suggest that the symbiotic microbes boosted clover growth, but did not result in excess production of nitrogen compounds that other plants growing nearby could hypothetically use. The researchers also grew some clover in potting soil and noted certain differences in the symbiotic relationship when comparing the plants grown in regolith versus soil.

These findings suggest the possibility that symbiosis between plants and nitrogen-fixing bacteria could aid agriculture on Mars. Future research could continue to explore such relationships with other crops and address issues with plant toxicity in regolith.

The authors add: “This study shows that nodule forming bacteria Sinorhizobium meliloti has been shown to nodulate in Martian regolith, significantly enhancing growth of clover (Melilotus officinalis) in a greenhouse assay. This work increases our understanding of how plant and microbe interactions will help aid efforts to terraform regolith on Mars.”



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Plastic shopping bags release thousands of dissolved compounds in sunlight

Plastic shopping bags release thousands of dissolved compounds in sunlight

Although plastics are durable and strong, a little sunlight can split them apart into microscopic pieces and spur reactions, producing new molecules that can end up in the environment. But how the polymers and additives in these materials influence this process is a mystery. Now, researchers reporting in ACS’ Environmental Science & Technology show that additives in commercial shopping bags boost sunlight’s ability to convert these solid materials into thousands of dissolved compounds within days.

Once plastic pollution gets into the environment, its fate is still largely unknown, especially in aquatic ecosystems. Some of the plastic items, such as polyethylene shopping bags, float in water, which exposes them directly to the sun’s rays. Previous researchers have shown that the pure polymers commonly used to make these items produce water-soluble molecules and gases when placed in ultraviolet light, a component of sunlight. However, plastics in consumer goods aren’t pure; a variety of carbon-based organic additives and mineral additives are mixed in to give them color or make them more stable. So, Collin Ward and colleagues wanted to see exactly how the composition of single-use shopping bags influenced the dissolved compounds generated by sunlight over short periods.

With X-ray diffraction, the researchers examined four polyethylene plastic bags from big-box retailers and a pure polyethylene polymer film for mineral additives. No additives were identified in the pure polymer, but calcium carbonate and titanium dioxide were found in three of the bags, and only calcium carbonate was found in the fourth bag. Next, the researchers put pieces of the plastic bags and the polymer into separate containers with water, and then in the dark or under simulated daylight for up to a week. Some water-soluble compounds were released from the different pieces in the dark. But in sunlight, more compounds were released, ranging from 5,000 to 15,000 dissolved compounds, which equates to 1.1-fold to 50-fold increases over the number of compounds released in the dark. Of the approximately 9,000 molecules generated by the pure polymer when exposed to sunlight, only about a quarter overlapped with those from the bags. Based on these results, the researchers say that sunlight’s reactions with solid plastics can transform them into a plethora of water-soluble compounds whose levels and identities vary, depending on the additives used.

The authors acknowledge funding from The Seaver Institute, the Gerstner Family Foundation, the Woods Hole Oceanographic Institution, and the National Science Foundation’s Graduate Research Fellowship ProgramDivision of Chemistry and Division of Materials Research.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.



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Extending LIGO’s Reach Into the Cosmos

Extending LIGO's Reach Into the Cosmos

Since LIGO’s groundbreaking detection, in 2015, of gravitational waves produced by a pair of colliding black holes, the observatory, together with its European partner facility Virgo, has detected dozens of similar cosmic rumblings that send ripples through space and time.

In the future, as more and more upgrades are made to the National Science Foundation-funded LIGO observatories—one in Hanford, Washington, and the other in Livingston, Louisiana—the facilities are expected to detect increasingly large numbers of these extreme cosmic events. These observations will help solve fundamental mysteries about our universe, such as how black holes form and how the ingredients of our universe are manufactured.

One important factor in increasing the sensitivity of the observatories involves the coatings on the glass mirrors that lie at the heart of the instruments. Each 40-kilogram (88-pound) mirror (there are four in each detector at the two LIGO observatories) is coated with reflective materials that essentially turn the glass into mirrors. The mirrors reflect laser beams that are sensitive to passing gravitational waves.

Generally, the more reflective the mirrors the more sensitive the instrument, but there is a catch: The coatings that make the mirrors reflective also can lead to background noise in the instrument—noise that masks gravitational-wave signals of interest.

Now, a new study by the LIGO team describes a new type of mirror coating made of titanium oxide and germanium oxide and outlines how it can reduce background noise in LIGO’s mirrors by a factor of two, thereby increasing the volume of space that LIGO can probe by a factor of eight.

“We wanted to find a material at the edge of what is possible today,” says Gabriele Vajente, a LIGO senior research scientist at Caltech and lead author of a paper about the work that appears in the journal Physical Review Letters. “Our ability to study the astronomically large scale of the universe is limited by what happens in this very tiny microscopic space.”

“With these new coatings, we expect to be able to increase the detection rate of gravitational waves from once a week to once a day or more,” says David Reitze, executive director of LIGO Laboratory at Caltech.

The research, which may have future applications in the fields of telecommunications and semiconductors, was a collaboration between Caltech; Colorado State University; the University of Montreal; and Stanford University, whose synchrotron at the SLAC National Accelerator Laboratory was used in the characterization of the coatings.

LIGO detects ripples in space-time using detectors called interferometers. In this setup, a powerful laser beam is split into two: each beam travels down one arm of a large L-shaped vacuum enclosure toward mirrors 4 kilometers away. The mirrors reflect the laser beams back to the source from which they originated. When gravitational waves pass by, they will stretch and squeezes space by nearly imperceptible and yet detectable amounts (much less than the width of a proton). The perturbations change the timing of the arrival of the two laser beams back at the source.

Any jiggling in the mirrors themselves—even the microscopic thermal vibrations of the atoms in the mirrors’ coatings—can affect the timing of the laser beams’ arrival and make it hard to isolate the gravitational-wave signals.

“Every time light passes between two different materials, a fraction of that light is reflected,” says Vajente. “This is the same thing that happens in your windows: you can see your faint reflection in the glass. By adding multiple layers of different materials, we can reinforce each reflection and make our mirrors up to 99.999 percent reflective.”

“What’s important about this work is that we developed a new way to better test the materials,” says Vajente. “We can now test the properties of a new material in about eight hours, completely automated, when before it took almost a week. This allowed us to explore the periodic table by trying a lot of different materials and a lot of combinations. Some of the materials we tried didn’t work, but this gave us insights into what properties might be important.”

In the end, the scientists discovered that a coating material made from a combination of titanium oxide and germanium oxide dissipated the least energy (the equivalent of reducing thermal vibrations).

“We tailored the fabrication process to meet the stringent demands in optical quality and reduced thermal noise of the mirror coatings,” says Carmen Menoni, professor at Colorado State University and member of the LIGO Scientific Collaboration. Menoni and her colleagues at Colorado State used a method called ion beam sputtering to coat the mirrors. In this process, atoms of titanium and germanium are peeled away from a source, combined with oxygen, and then deposited onto the glass to create thin layers of atoms.

The new coating may be used for LIGO’s fifth observing run, which will begin in the middle of the decade as part of the Advanced LIGO Plus program. Meanwhile, LIGO’s fourth observing run, the last in the Advanced LIGO campaign, is expected to commence in the summer of 2022.

“This is a game changer for Advanced LIGO Plus,” says Reitze. “And this is a great example of how LIGO relies heavily on cutting-edge optics and materials science research and development. This is the biggest advance in precision optical coating development for LIGO in the past 20 years.”

The study, titled, “Low Mechanical Loss TiO2:GeO2 Coatings for Reduced Thermal Noise in Gravitational Wave Interferometers,” was funded by the NSF and the Gordon and Betty Moore Foundation.



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