‘Metabolic switch’ may pave way for obesity, cancer treatments

Researchers have discovered a method for modifying the function of an enzyme crucial to fat production.

The find could lead to more effective treatments for childhood obesity and cancer.

While the research was in fruit fly larvae, being able to speed up or slow down lipid metabolism could have significant implications for human health, says Hua Bai, an associate professor of genetics, development and cell biology at Iowa State University.

“We’ve identified what’s basically a metabolic switch. It’s like the accelerator on a car,” he says.

The focus of Bai’s research lab is the cellular and molecular mechanisms that cause animals to age. That was the initial intent of studying fatty acid synthase, an enzyme that plays a role in de novo lipogenesis, which is the process of turning excess dietary carbohydrates into fat. Typically, levels of fatty acid synthase rise and fall based on an animal’s cellular needs and diet.

Surprisingly, the researchers noticed that early in a fruit fly’s development, de novo lipogenesis increases without an accompanying boost in the expression of fatty acid synthase. That suggested there must be some other factor at play, Bai says.

After proteins such as fatty acid synthase are created based on genetic code, their function can be altered by one of several different types of post-translational modification. Bai’s team found one of those processes, acetylation, affected one of the 2,540 amino acids that combine to make fatty acid synthase, changing how effective it was at producing fat.

The research appears in the Proceedings of the National Academy of Sciences.

In addition to its role in obesity, elevated levels of de novo lipogenesis are linked to cancer, so controlling it through a single amino acid could lead to highly targeted treatments, Bai says.

“Fine tuning the acetylation levels of fatty acid synthase would be a much more precise treatment than blocking the entire protein,” he says.

It’s not certain that the processes Bai’s team studied will work the same in humans, but the two species’ genomes are similar, which is part of the reason fruit flies are a common research subject. Still, capitalizing on the discovery to treat human disease is many years away, he says.

“The potential is high, but further testing is needed in other animals,” he says.

Source: Iowa State University

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Early life tastes tied to adult food preferences

There’s a strong relationship between diet in early life and food preferences in adulthood, research with mice finds.

The study in Science Advances highlights the importance of early exposure to a variety of tastes and identifies the neural basis regulating preferences for favorite foods, providing important new information about the relationship between nutrition and brain function.

Previous investigations of human infants hinted at the effect of early taste experience on food preference later in life. However, no previous study examined the neural bases of this phenomenon. This study looks at the neural bases of taste preference and provides findings that could form a basis to understanding the neural processes involved in taste preference.

The biology of the gustatory system is similar across all mammals. By using a rodent model, researchers from the Renaissance School of Medicine at Stony Brook University exposed groups of mice to a variety of taste solutions for one week. They exposed groups as either weanlings (early exposure) or as adults (late exposure). After the one week experiencing a variety of tastes, they returned the groups to their regular diet, which contained balanced nutrients but was not rich in taste. For comparison, a control group of mice was raised only on the regular, blander diet.

“Our research is directed at assessing whether and how the gustatory experience and diet influence brain development. This study shows that the gustatory experience has fundamental effects on the brain. The next steps will be to determine how different diets such as a high fat, or a high sugar or high salt, may influence taste preferences and neural activity,” explains Arianna Maffei, senior author and professor in the department of neurobiology and behavior.

Food preferences

Maffei, lead author Hillary Schiff, and colleagues increased taste variety in the healthy diets of mice and found that the development of neural circuits and taste preference are influenced by all aspects of the gustatory experience: sensations in the mouth, smell, and gut-brain relations.

Several weeks after exposing the groups to the one-week taste variety, the investigators measured preference for a sweet solution compared to water. Mice who experienced taste variety early in life had a stronger preference for sweet tastes in adulthood compared to the control group. This change preference depended on a combination of taste, smell, and gut-to-brain signals, and was specific to early exposure taste. Mice exposed to taste variety as adults did not show different sweet preferences from their age-matched control group.

These results indicate that taste experience influences preference, but only if given within a restricted time window.

The gustatory cortex

The researchers also recorded the activity of neurons in the gustatory cortex of all the subjects. This part of the brain is involved in taste perception and decisions about ingesting or rejecting foods. The recorded activity showed that the shift in sweet preference was associated with differences in the activity of inhibitory neurons of adult mice.

This led to the question of whether manipulating these inhibitory neurons in adulthood can re-open the window of sensitivity to the taste experience.

To answer this question, the research team injected a substance into the gustatory cortex that breaks down perineuronal nets, which are webs of proteins that accumulate around inhibitory neurons early in life. Once established, these nets play a key role in limiting plasticity—the ability to change in response to stimuli at inhibitory synapses.

When adult mice without perineuronal nets in the gustatory cortex were exposed to the taste variety, they showed a similar change in sweet preference as the group exposed earlier in life. This manipulation “rejuvenated” inhibitory synapses in the gustatory cortex and restored plasticity in response to taste experience, which confirmed the importance of maturation and plasticity in inhibitory circuits for the development of taste preference in the experimental model.

“It was striking to discover how long-lasting the effects of early experience with taste were in the young groups,” says Schiff. “The presence of a ‘critical period’ of the life cycle for the development of taste preference was a unique and exciting discovery. The prevailing view from other studies prior to this finding was that taste does not have a defined window of heightened sensitivity to experience like other sensory systems such as vision, hearing, and touch.”

From mice to humans

The authors maintain that while they conducted the study in mice, the results inform scientists on the fundamental biological aspects of experiences with taste that extends beyond animal models and to humans.

“The development of taste preference requires a full gustatory experience,” adds Maffei. “This includes the detection of taste in the mouth, its association with smell, and the activation of gastrointestinal sensations. All these aspects influence the activity of brain circuits, promoting their healthy development.”

Regarding humans, Maffei points out that we often favor food from our childhood, highlighting important cultural aspects of our taste experience. Additionally, in the public health realm, several neurodevelopmental and neurodegenerative disorders are often associated with hyper- or hyposensitivity to gustatory stimuli, suggesting links between taste and brain function in health and disease.

“Expanding our knowledge of the developmental neural circuits for tastes—as studies like this do—will contribute to our understanding of food choices, eating disorders, and diseases associated with brain disorders,” emphasizes Maffei.

Schiff, Maffei, and collaborators conclude that their overall experimental results establish a fundamental link between the gustatory experience, sweet preference, inhibitory plasticity, circuit function, and the importance of early life nutrition in setting taste preferences.

The research had support from the National Institute on Deafness and Other Communication Disorders and from the National Institute of Neurological Disorders and Stroke at the National Institutes of Health.

Source: Stony Brook University

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Extinct species recovery on Madagascar would take 3 million years

It would take three million years to recover the number of species that went extinct due to human activity on Madagascar, a new study shows.

The study, published in Nature Communications, also projects that if currently threatened species go extinct on Madagascar, recovering them would take more than 20 million years—much longer than what has previously been found on any other island archipelago in the world.

From unique baobab species to lemurs, the island of Madagascar is one of the world’s most important biodiversity hotspots. Approximately 90% of its species of plants and animals aren’t found anywhere else. After humans settled on the island about 2,500 years ago, Madagascar experienced many extinctions, including giant lemurs, elephant birds, and dwarf hippos.

Yet unlike most islands, Madagascar’s fauna is still relatively intact. Over two hundred species of mammals still survive on the island, including unique species such as the fossa and the ring-tailed lemur.

Alarmingly, over half of these species are threatened with extinction, primarily from habitat transformation for agriculture. How much has human activity perturbed Madagascar away from its past state, and what is at stake if environmental change continues?

A team of biologists and paleontologists from Europe, Madagascar, and the United States set out to answer this question by building an unprecedented new dataset describing the evolutionary relationships of all species of mammals that were present on Madagascar at the time that humans colonized the island.

Coauthor Liliana M. Dávalos, a PhD in the department of ecology and evolution at Stony Brook University, helped design the study, interpreted a previously published lemur phylogeny, and analyzed prospects for new species discovery in Madagascar.

The dataset includes species that have already gone extinct and are only known from fossils, as well as all living species of Malagasy mammals. The researchers identified 249 species in total, 30 of which already are extinct. Over 120 of the 219 species of mammals that remain on the island today are currently classified as threatened with extinction by the IUCN Red List, due to habitat destruction, climate change, and hunting.

Using a computer simulation model based on island biogeography theory, the team, led by Nathan Michielsen and Luis Valente from the University of Groningen and Naturalis Biodiversity Center, both in the Netherlands, found that it would take approximately three million years to regain the number of mammal species that were lost from Madagascar in the time since humans arrived.

The research team also determined through the computer simulation that if currently threatened species go extinct, it would take much longer: about 23 million years of evolution would be needed to recover the same number of species. Just in the last decade, this figure has increased by several million years, as human impact on the island continues to grow.

The amount of time it would take to recover this mammalian diversity surprised the international team of scientists.

“These staggering results highlight the importance of effective conservation efforts in Madagascar.,” says Dávalos.

“It was already known that Madagascar was a hotspot of biodiversity, but this new research puts into context just how valuable this diversity is,” Valente says. “The time it would take to recover this diversity is much longer than what previous studies have found on other islands, such as New Zealand or in the Caribbean.”

The study findings ultimately suggest that an extinction wave with deep evolutionary impact is imminent on Madagascar, unless immediate conservation actions are taken.

The good news? The computer simulation model shows that with adequate conservation action, we may still preserve over 20 million years of unique evolutionary history on the island.

Source: Stony Brook University

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Most clergy support medical care for depression

About 90% of clergy members in a recent survey had a medical understanding of depression.

About 10% said they’d counsel their congregation to address depression only through religious means.

“We consider this good news,” Mark Chaves, professor of sociology, religious studies, and divinity at Duke University, and coauthor of a paper on the survey.

“We’ve known for a while that a lot of people bring their mental health challenges to clergy,” Chaves says. “There’s been concern about what clergy have been telling them. Have they been telling them just to pray, or to see a doctor? This should allay concerns.”

The study appears in JAMA Psychiatry. Coauthor Anna Holleman, a postdoctoral research associate, says survey results largely held true across denominations.

“We couldn’t find any subset of clergy in which anything but a small minority rejected medical wisdom,” Holleman says.

Study data came from Duke’s National Survey of Religious Leaders, a nationally representative survey of clergy serving US congregations from across the religious spectrum. The survey, funded by the John Templeton Foundation, took place in 2019 and 2020—largely prior to the COVID-19 pandemic and its associated uptick in mental health challenges. The survey drew responses from 1,600 congregational leaders, 890 of whom were their congregation’s primary leader. The survey cooperation rate for primary leaders was 70%. These results use responses from those 890 primary leaders.

The new study is the first to survey a nationally representative sample of clergy specifically on the issue of depression, the authors say. The results include clergy opinions about both the causes of depression and appropriate treatments for it, Holleman says. Few clergy disputed conventional medical wisdom about either the cause or treatment of depression. At the same time, more endorsed mixing both medical and religious responses to it—combining a doctor’s treatment with prayer and church attendance—than believe in both medical and religious causes of depression.

That mixing of medical and religious responses to depression is not limited to clergy, Holleman notes.

“Even some secular mental health professionals recognize that people’s spiritual or religious activities can be assets that people already have and can draw on in beneficial ways,” she says. “We see a lot of potential here for constructive collaboration between mental health professionals and clergy.”

The small number of clergy who rejected medical advice in favor of religious options in the treatment of depression were largely leaders of Black protestant and white evangelical congregations. Even among those groups, though, only a small minority—about 15%—endorsed substituting religious for medical responses.

A divide between religious and mental health professionals has existed for at least a century, though their views about mental illness have converged somewhat in the last couple of decades as more information about biological causes of depression and the effectiveness of medication has become widely available, says Harold G. Koenig, professor of psychiatry and behavioral sciences who studies the effects of religion and spirituality on health.

Koenig, who is not connected to the clergy study, says its results are heartening.

“The majority of mental health professionals are not religious, and that’s a problem because the majority of their patients are,” Koenig says. “So it’s encouraging to see the vast majority of clergy see depression as something that is more likely to have biological or situational rather than religious causes.”

“Life is hard. Things happen,” Koenig says. “You get disappointed. You get divorced. So religion can be extremely helpful in dealing with these issues. But some folks need more than religion—they need medication,” he says. “You need treatment. You can’t pray it all away.”

Source: Duke University

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Isolation may be a dementia risk factor, but tech could help

Two new studies add to the evidence that social isolation is a substantial risk factor for dementia in community-dwelling  older adults, new research shows.

The research also identifies technology as an effective way to intervene.

Collectively, the studies don’t establish a direct cause and effect between dementia and social isolation, defined as lack of social contact and interactions with people on a regular basis. But, the researchers say, the studies strengthen observations that such isolation increases the risk of dementia, and suggest that relatively simple efforts to increase social support of older adults—such as texting and use of email—may reduce that risk.

In the United States, an estimated 1 in 4 people over age 65 experience social isolation, according to the National Institute on Aging.

Social connections matter for our cognitive health, and it is potentially easily modifiable for older adults without the use of medication,” says Thomas Cudjoe, assistant professor of medicine at the Johns Hopkins University School of Medicine and senior author of both of the new studies.

The first study, published in the Journal of the American Geriatrics Society, used data collected on a group of 5,022 Medicare beneficiaries for a long-term study known as the National Health and Aging Trends, which began in 2011. All participants were 65 or older, and were asked to complete an annual two-hour, in-person interview to assess cognitive function, health status, and overall well-being.

At the initial interview, 23% of the 5,022 participants were socially isolated and showed no signs of dementia. However, by the end of this nine-year study, 21% of the total sample of participants had developed dementia. The researchers concluded that risk of developing dementia over nine years was 27% higher among socially isolated older adults compared with older adults who were not socially isolated.

“Socially isolated older adults have smaller social networks, live alone, and have limited participation in social activities,” says Alison Huang, senior research associate at the Johns Hopkins Bloomberg School of Public Health. “One possible explanation is that having fewer opportunities to socialize with others decreases cognitive engagement as well, potentially contributing to increased risk of dementia.”

Interventions to reduce that risk are possible, according to results of the second study, published in the Journal of the American Geriatrics Society. Specifically, researchers found the use of communications technology such as telephone and email lowered the risk for social isolation.

Researchers for the second study used data from participants in the same National Health and Aging Trends study, and found that more than 70% of people age 65 and up who were not socially isolated at their initial appointment had a working cellphone and/or computer, and regularly used email or texting to initiate and respond to others.

Over the four-year research period for this second study, older adults who had access to such technology consistently showed a 31% lower risk for social isolation than the rest of the cohort.

“Basic communications technology is a great tool to combat social isolation,” says Mfon Umoh, a postdoctoral fellow in geriatric medicine at the Johns Hopkins University School of Medicine. “This study shows that access and use of simple technologies are important factors that protect older adults against social isolation, which is associated with significant health risks. This is encouraging because it means simple interventions may be meaningful.”

Social isolation has gained significant attention in the past decade, especially due to restrictions implemented for the COVID-19 pandemic, but more work needs to be done to identify at-risk populations and create tools for providers and caregivers to minimize risk, the researchers say. Future research in this area should focus on increased risks based on biological sex, physical limitations, race, and income level.

Funding for the studies came from the Caryl & George Bernstein Human Aging Project, the Johns Hopkins University Center for Innovative Medicine, the National Center for Advancing Translational Sciences, the National Institute on Aging, the Secunda Family Foundation, the Patient-Centered Care for Older Adults with Multiple Chronic Conditions, and the National Institute on Minority Health and Health Disparities.

The authors have no conflicts of interest to report.

Source: Johns Hopkins University

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Baby poop shows vaxxed moms’ breast milk offers COVID protection

New research provides more evidence that the breast milk of people vaccinated against COVID-19 protects infants too young to receive the vaccine.

For the study, which follows up on findings published in 2021 that showed the breast milk of vaccinated people contained antibodies against SARS-CoV-2, the virus that causes COVID-19, researchers analyzed the stool of infants that consumed this breast milk and found SARS-CoV-2 antibodies there as well.

“Our first study showed there were SARS-CoV-2 antibodies in the breast milk, but we couldn’t say if those antibodies were getting through the babies’ gastrointestinal tract and possibly providing protection there,” says Joseph Larkin III, an associate professor in the department of microbiology and cell science at the University of Florida and senior author of the study published in the Journal of Perinatology.

Using a technique called a neutralization assay, the researchers showed that the antibodies found in the infants’ stool offered protection against the virus.

The assay begins by isolating antibodies from the stool and adding them to a special line of cells that have the kind of receptors the SARS-CoV-2 virus uses to enter the cell. The researchers then introduce a SARS-CoV-2 pseudovirus, which acts like the virus that causes COVID-19 but is safer to use in the lab. The pseudovirus is fluorescent, so when it binds to a cell, the cell lights up.

“We saw that when the antibodies were present, there were fewer fluorescent cells compared to our controls where no antibodies were present,” says Lauren Stafford, a doctoral student in Larkin’s lab and a first author of the study.

“The antibodies run interference and don’t let the virus get to the cells,” Larkin adds.

While the virus that causes COVID-19 is often thought of as mainly affecting the lungs, it can also invade the gut, which is why finding antibodies there is significant, the researchers say.

“The antibodies ingested through breast milk may provide a protective coating in the infants’ mouths and gastrointestinal tract,” says Vivian Valcarce Luaces, the study’s other first author and a postdoctoral fellowship trainee in neonatology.

The study also measured and tested antibodies found in the mothers’ blood plasma and breast milk soon after vaccination and then again about six months later. The researchers found that the antibodies in the plasma and milk of vaccinated people were better able to neutralize the virus, though they also observed that antibody levels decreased at the six-month mark, which other vaccine studies have found as well.

Coauthor Josef Neu, a professor in the UF College of Medicine department of pediatrics, division of neonatology, says the first and second studies together give a more complete picture of how vaccinating against COVID-19 during pregnancy and breastfeeding may be protective for parent and child.

“In our research, we’re following the journey of the antibodies, from the time they are produced in mom after vaccination and now through the baby’s digestive system. The next question is whether those babies are less likely to get COVID-19,” Neu says.

The researchers say larger studies are needed to answer that question, as this latest study included 37 mothers and 25 infants, a relatively small number of participants.

However, the study adds to a growing body of research revealing how vaccination against COVID-19 during pregnancy and breastfeeding may protect newborns, the researchers say. Currently children under sixth months of age cannot receive the vaccine, so breast milk may be the only avenue for providing immunity.

The Centers for Disease Control and Prevention recommends COVID-19 vaccination for people who are pregnant, breastfeeding, trying to get pregnant, or who may become pregnant in the future. According to the CDC, as of late November 2022, just over 70% of pregnant people in the United States had completed the primary series of COVID-19 vaccines, though only 14% had received the bivalent booster.

Grants from the Children’s Miracle Network and The Gerber Foundation funded the work.

Source: University of Florida

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EU needs major investment to hit emissions target

If Europe fails to invest 302 billion euros in climate-relevant infrastructure over the next two years, it will not reach its target of net-zero greenhouse gas emissions by 2050, researchers report.

Both the European Union and Switzerland have set themselves the goal of becoming climate neutral by 2050 and of reducing their greenhouse gas emissions to net zero.

To achieve this target, major investments in power generation from renewable energies, electricity grids, storage capacities, and other climate-relevant infrastructure are required.

However, it has been unclear until now just how much investment will be necessary over the next 15 years and which areas are the most important.

A new meta-study published in Nature Climate Change fills this gap in knowledge.

“Investment in green infrastructure needs to urgently increase by 87 billion euros per year compared with the levels of recent years. This is an increase of more than one third,” says first author Lena Klaaßen, a doctoral student at ETH Zurich’s Climate Finance and Policy Group.

Investments in solar and wind

Although the money is readily available—given the size of the European equity and bond markets—the main challenge is to put the necessary political policies in place quickly enough to ensure that capital flows into the right projects.

The researchers built on 56 relevant technology and investment studies from academia, industry, and the public sector. They focused on the countries of the EU, but also took into account data on the UK, Norway, and Switzerland. The overall European trends are therefore also relevant for Switzerland.

The most dramatic increase in the need for investment is in power generation from renewable energies.

“In order to drive forward the decarbonization of all areas of life, around 75 billion euros needs to be invested in solar and wind power plants in the coming years. This is 24 billion euros more per year than in the recent past,” says professor Bjarne Steffen.

The situation is similar in the expansion of distribution networks and the railway. In these areas, too, 40 to 60% additional financial flows are required compared to the 2016–2020 period in order to expand electrification and to shift

The war in Ukraine is reinforcing these trends further, the researchers say.

“In order to import as little gas as possible from Russia, Europe would have to invest around 10 billion euros more per year in solar energy and wind power. In comparison, significantly less investment—around 1.5 billion euros per year—is needed in additional natural gas infrastructure such as LNG terminals,” Steffen says.

Carbon storage investments

According to the study, fossil fuels such as coal, oil, and gas are likely to tie up less capital in future in Europe. The investment required in conventional power plants in particular is set to fall by 70% within the space of a few years.

What can policymakers do to expedite the increase in capital made available for the expansion of green infrastructure?

“Political measures should be tailored to funding in those sectors where there is the greatest need for investment,” explains Klaaßen.

This is not a matter of course today, she says. For example, existing regulations in the EU focus on identifying sustainable securities, despite the fact that important climate-relevant infrastructure is not at all financed via the equity markets.

The expansion of renewable energies, in contrast, is often made possible by private investors such as pension funds and banks. The public sector should minimize their risk through revenue guarantees and by making approval procedures as quick and predictable as possible. Public investment in new technologies such as CO2 storage can also help to encourage private investors to venture into these areas.

Source: Christoph Elhardt for ETH Zurich

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Electric vehicles would benefit 90% of US households

More than 90% of vehicle-owning households in the United States would see a reduction in the percentage of income they spend on transportation energy if they switched to electric vehicles, research finds.

And more than 90% of households that replace gas-powered vehicles with EVs would also reduce the amount of climate-warming greenhouse gases they generate, the findings show.

However, more than half of the lowest-income US households (an estimated 8.3 million households) would continue to experience high transportation energy burdens, defined in this study as spending more than 4% of household income on filling the tank or charging up.

US map color-codes transportation energy burden by location, with most benefits for households on West Coast, South, Mid-Atlantic and New England. Central portion of country lower, and lowest of all in Alaska.
Map of percentage change in transportation energy burden from current on-road vehicle stock to a new battery-electric vehicle. Negative percentages indicate energy cost savings for EVs compared to gasoline powered vehicles. Areas with the greatest savings, shown in green, include the West Coast states and parts of the East and South. Transportation energy burden is the percentage of household income spent on fueling with gasoline or charging with electricity. (Credit: Adapted from Vega-Perkins et al. in Environmental Research Letters, January 2023.

“Our results confirm the potential for widespread benefits from EV adoption,” says corresponding author of the study Joshua Newell, an urban geographer at the University of Michigan Center for Sustainable Systems, part of the School for Environment and Sustainability.

“However, EV ownership in the US has thus far been dominated by households with higher incomes and education levels, leaving the most vulnerable populations behind. Policy interventions are needed to increase EV accessibility so that all Americans can benefit from the EV transition.”

The new study appears in the journal Environmental Research Letters. It is the first study to consider the spatial variation of both EV energy costs and greenhouse gas emissions across the country.

It’s also the first study to examine EV energy costs through the lens of distributive justice by calculating the EV energy burden (percentage of income spent on EV charging) for the entire United States. Distributive justice concerns the fair distribution of benefits and burdens.

EVs currently account for about 1% of the cars, SUVs, and pickups on American roads. If all those vehicles were replaced with new EVs, the transportation energy burdens and associated greenhouse gas emissions would vary widely from place to place, according to the new study.

Reductions in both transportation energy burden and GHG emissions would be especially pronounced on the West Coast and in parts of the Northeast, due largely to cleaner energy grids and lower electricity prices.

Households in some locations could reduce their annual transportation-energy costs by $600 or more, and cut their annual carbon footprint by more than 4.1 metric tons of carbon dioxide equivalents, by buying a new EV.

But lower-income households in other parts of the country wouldn’t fare as well, Newell says.

Very high EV transportation energy burdens, ranging from 10% to 64%, would persist for the lowest-income households and would be concentrated in the Midwest and in the two states with the highest electricity prices: Hawaii and Alaska.

Of US households, 8% (an estimated 9.6 million) would see low savings in both transportation energy burden and greenhouse gas emissions by choosing an EV. “Both low” households are scattered across the country, with about half of them in Midwest states.

Factors that contribute to those low EV savings include cold winter temperatures that affect battery performance, electrical grids that rely largely on fossil fuels, or electricity prices that are higher relative to gasoline prices.

According to the study, the lowest-income households would continue to experience the highest transportation energy burdens. Essentially all households with incomes of less than 30% of the local median would experience moderate or high EV energy burdens.

“We identified disparities that will require targeted policies to promote energy justice in lower-income communities—including the subsidizing of charging infrastructure—as well as strategies to reduce electricity costs and increase the availability of low-carbon transportation modes such as public transit, bicycling, and car sharing,” says lead author Jesse Vega-Perkins, who did the work for a master’s thesis at the University of Michigan School for Environment and Sustainability.

“Our analysis indicates that future grid decarbonization, current and future fuel prices, and charging accessibility will impact the extent to which EV benefits will be realized, including lowering transportation energy burdens for low-income households,” says senior author Greg Keoleian, director of the university’s Center for Sustainable Systems.

The study used a geospatial model to evaluate three factors associated with the EV transition: transportation energy burden, fuel costs (meaning the cost of gasoline or the electricity needed to charge an EV), and greenhouse gas emissions.

The analysis does not include vehicle purchase cost. Total cost of ownership of EVs is the focus of a current study by the Center for Sustainable Systems.

The researchers calculated transportation energy burdens and lifetime greenhouse gas emissions of new battery-electric and internal-combustion vehicles at the census tract level. Then they compared the energy burdens of the new vehicles to the energy burdens of the current on-road vehicle stock. Finally, they compared the spatial variation and extent of energy burdens and greenhouse gas emissions for EVs and internal-combustion vehicles across the US.

Transportation accounts for the largest portion of the greenhouse gases emitted in the United States, with direct emissions from passenger vehicles and light-duty trucks comprising roughly 16% of US emissions. Electrification is seen as the primary pathway to reducing those emissions.

The study had support from the university’s School for Environment and Sustainability.

Source: University of Michigan

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Machine learning maps risk to sharks from fishing lines

Researchers are using machine learning to map where sharks face the most risk from longline fishing.

The ocean can be a dangerous place, even for a shark. Despite sitting at the top of the food chain, these predators are now reeling from destructive human activities like overfishing, pollution, and climate change.

The new research used data from regional fisheries management organizations and machine learning algorithms. The findings in Frontiers in Marine Science highlight key regions where sharks can be protected with minimal impact on tuna fisheries.

Sharks take the bait

Offshore longline fisheries take an especially heavy toll on ocean life. The non-selective technique has the highest rate of shark bycatch.

“Longline fishing gear is exactly what it sounds like: a long line with lots of hooks attached to it that are baited. And they can be left in the water, waiting for fish to bite, for a very long time,” explains co-lead author Darcy Bradley, who heads the Ocean & Fisheries Program at the Environmental Markets Lab (emLab) at the University of California, Santa Barbara.

These baited hooks catch predators like tuna, but many nearby sharks will also converge on the bait.

Rather than simply report how many sharks were caught and where, the authors aimed to assess the relative risk sharks faced across different areas of the ocean.

“One of the main questions was ‘Where is the risk for catching sharks the highest, and does that overlap with fishing effort?’” says co-lead author Echelle Burns, a project scientist at emLab.

To answer this, Burns, Bradley, and coauthor Lennon Thomas (also at emLab) went hunting for data on longline fisheries. They sourced publicly available data from tuna regional fisheries management organizations. These intergovernmental institutions manage, collect data, and perform scientific assessments for tuna and tuna-like species.

The authors compiled data on shark catch from industrial longline fishing across all the world’s tuna fisheries into one comprehensive resource. This was quite a task. Each fisheries management organization operates differently, meaning their data isn’t always in the same format.

“Now anyone who’s interested in shark catches and other happenings in these global longline fisheries has access to that information,” Bradley says.

Even top predators face risks

The authors paired spatial shark catch data with environmental data like sea-surface temperature and factors correlated with food abundance. They also included economic data like ex vessel price—the price that fishers receive directly for their catch—for different shark species each year.

“Because you can’t catch a shark where it doesn’t live,” Bradley adds, “we used species distribution models to delineate where different sharks actually live in the ocean to inform our risk assessment.”

Still, there were a lot of unknowns. Not every fishing vessel has an impartial observer recording catch for the fisheries management organizations. And not every report is completely accurate.

So Burns, Bradley, and Thomas used a model to fill in the gaps, recognize trends and draw conclusions from this incomplete data. “The whole reason to use a model is because we have imperfect data,” Bradley says. “If we knew everything we wouldn’t need a model.”

This was a new approach to estimating the interactions between fisheries and marine species. Using machine learning enabled the team to extrapolate trends from their messy datasets. First, the model assessed whether a shark species was present in an area, and if so, how likely it was to be caught there. Then it looked at how many sharks of each species were caught in an area.

The authors prioritized predictive power in this study. “Our goal was to identify where sharks are at the highest risk of being caught by tuna longline fisheries,” Bradley explains. “For this study, we were not trying to understand the extent to which various factors influence this risk.”

The authors used a random forest model, which combines the outputs of many decision trees. Each decision tree considers a different variable, and its outcome is a vote for the final prediction.

“The basic idea is that a bunch of poor decision-makers, the trees, can share information to ultimately make a better decision: the forest,” Bradley says. While this method doesn’t provide a clear picture of how each factor influences the system, it is very good at making sense of messy and incomplete datasets. What emerged was a map of catch risk for shark populations across the globe.

Good for sharks, good for fishers

Tunas and sharks are both predators and target similar prey, so they’re often found together. But while they may share some traits, sharks and tunas are fundamentally different types of animals. Tunas grow quickly and produce many offspring, while sharks mature relatively late and reproduce slowly.

As a result, tuna can withstand much higher fishing pressures than sharks, and even a small impact on shark numbers can affect the population of a threatened species.

Fortunately, the scientists found that hotspots for longline-shark interactions didn’t correspond with preferred fishing grounds. “This suggests that we can design management strategies that can protect vulnerable and threatened shark species without having to close the most productive tuna fishing grounds,” Bradley says. The team found this particularly heartening, since it could encourage actions that help sharks while appealing to fishers as well.

Shark catch hotspots

The difference between hotspots and good fishing grounds could stem from those differences between tuna and sharks.

“For example, we noticed that some of the shark catch hotspots overlap with areas that play a critical role in a shark’s life cycle,” Thomas says. Take the ocean off the coast of Namibia, a well-known nursery habitat and juvenile feeding ground for blue sharks.

In fact, blue sharks dominated interactions with longline fishing fleets. This common and widespread species contributed over 78% of the total shark catch reported by tuna regional fisheries management organizations between 2012 and 2020.

As a result, the majority of the paper’s findings for sharks as a whole are driven by blue shark catch in particular. This was one reason the authors investigated hotspots for 12 species individually in their supplementary materials.

The team is working on a follow-up study estimating global shark mortality due to fishing as a whole—not just longline. They also plan to assess whether regulations have helped prevent shark catch. What’s more, this paper’s random forest model can provide insights on other species threatened by overfishing.

Better data will allow the team to improve their model, but it’s already providing useful lessons. For instance, we can design management strategies to protect vulnerable and threatened shark species without disrupting prime tuna fishing grounds.

“Making small adjustments to tuna fishing regulations to avoid shark catch hotspots could make a huge difference for shark populations in the future,” Burns says, “while also ensuring that the tuna fisheries remain successful.”

Source: UC Santa Barbara

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Could ‘morning after’ nasal spray block COVID?

Pinpointing the routes that the COVID-19 virus takes in and out of the nasal cavity could make possible a “morning after” spray to prevent infection, say researchers.

Imagine someone just coughed on you on a flight, in line at the store, anywhere. If only there were a “morning after” nasal spray that could knock out respiratory viruses’ ability to colonize your nose and throat.

“Our upper airways are the launchpad not only for infection of our lungs but for transmission to others,” says Peter Jackson, a Stanford School of Medicine professor of pathology and of microbiology and immunology. Jackson is senior author of the study in Cell with Raul Andino, professor of microbiology and immunology at UC San Francisco.

Inside the nose

The nose and airway are lined with epithelial tissue consisting mainly of three cell types: basal cells, goblet cells, and multiciliated cells, which make up about 80% of all cells in the nasal epithelium. Multiciliated cells form a protective barrier to keep viruses from entering the airway.

Jackson and his colleagues zoomed in on two structures found on multiciliated epithelial cells: cilia and microvilli. Although both are well known, neither structure has previously been implicated in how the virus enters or exits the cells lining the airway.

Cilia are spaghetti-like appendages sprouting from the outward-facing surfaces of various cells. A single nasal epithelial cell may host as many as 400 of these whiplike strands on its nasal-cavity-facing surface, all continuously beating in harmony. They’re topped by a thin layer of a protein called mucin—closely related to the key protein in mucus—and, atop that, a coat of mucus.

Mucin molecules can hook up with one another to form a mesh akin to an elastic, three-dimensional chain-link fence, preventing larger viruses such as SARS-CoV-2 from getting into upper-airway cells, Jackson says. The mucus coat entraps viral particles, bacteria, environmental debris, and cell-breakdown junk and keeps underlying cells moist.

Upper-airway epithelial cilia poke through this mucus layer, their synchronized beat generating a wave that pushes the mucus and its entrapped particles along, like a slow-moving river, to where it can be expectorated or, alternatively, swallowed and digested.

Another feature common to virtually all animal cells is microvilli, smaller spikes extending from the cell surface like little fingers. Microvilli can grab and transport subcellular particles and vesicles.

Organoids with cilia

To see, close up, what happens during a nascent viral infection, Jackson and his associates used a sophisticated tissue culture method to generate what they call airway epithelial organoids, which mimic normal airways. While lacking blood vessels and immune cells, these organoids otherwise fully recapitulate the architecture of the nasal epithelium, including an intact mucus-mucin layer and well-developed multiciliated cells.

The scientists inoculated the cultures by incubating them in the same dish with SARS-CoV-2. With light and electron microscopy and immunochemical staining, they monitored the epithelial cells for viral entry, replication and exit.

Only ciliated cells became infected. Electron microscopy showed that the virus initially attaches only to cilia. Six hours after organoids were incubated with SARS-CoV-2, many virus particles were dotting the cilia’s sides from the tips down. Even 24 hours after inoculation, the virus was replicating only in a few cells. It took 48 hours for massive replication to occur.

SARS-CoV-2 needs a full day or two to start replicating full-tilt in real life, too.

Depleting the cilia, by knocking down levels of a protein critical to cilia formation in nasal epithelial cells, severely slowed down SARS-CoV-2 infection.

“It’s clear that human ciliated nasal epithelial cells are the primary entry site for SARS-CoV-2 in nasal epithelial tissue,” Jackson says.

Suspecting that the delay in infection is due to the airway mucus-mucin barrier the virus has to cross, the researchers treated the airway organoids with a mucin-selective enzyme that breaks down the mucin-network mesh. It sped up virus entry at 24 hours from “barely detectable to easily detectable,” says Jackson, who concludes that eliminating mucin from this mesh prevented the mesh from blocking SARS-CoV-2 infection of the organoids.

In patients with a very rare disease called primary ciliary dyskinesia, whose ciliary beating capability is compromised or is no longer in sync, mucus flow loses its directionality.

In airway organoids generated from these patients, viral attachment to cilia resembled that seen in normal cells. At 24 hours post-inoculation, cell-infection rates were also similar to those of normal infected cells. Normal-looking microvilli bristled on cell surfaces.

But at 48 hours, SARS-CoV-2 was infecting far fewer cells overall—it could infect only the immediately surrounding cells—suggesting that once SARS-CoV-2 has started replicating within infected cells, the virus relies on adequate mucus flow to help it spread throughout the upper airways.

A May 2020 Nature Communications study, of which Jackson is a coauthor, showed that ACE2—the classic SARS-CoV-2-binding cell-surface molecule, or receptor—concentrates on the cilia of nasal epithelial cells. The new Cell study shows that SARS-CoV-2 bound to epithelial cilia via this receptor.

From there, Jackson says, the virus might slip past the mucus-mucin barrier in one of two ways: either by skipping down the side of cilia, hopscotch-style, from one ACE2 molecule to the next until it reaches the cell’s main body, fusing with the cell membrane there and climbing in; or by wedging its way into the cilium and riding an internal freight elevator down to the cell body.

“Once the virus gets through that barrier,” he says, “it can replicate freely in underlying cells.”

The researchers also find that SARS-CoV-2, once inside the cell, induces activity on the part of intracellular enzymes that causes microvilli to enlarge and branch, like crazy cactus plants, until their tips poke out above the mucus barrier. Their numbers increase. As soon as 24 hours post-inoculation, many altered microvilli, ordinarily less than half the length of cilia, have turned into huge, branching, tree-like structures the size of cilia or larger, and they’re decorated with attached viral particles that can shove off into the mucus-mucin layer, where they can float down the mucus river and infect other, more-distant cells.

The researchers pinpointed enzymes in the cell, massively switched on by SARS-CoV-2 infection, that were causing the microvilli’s transformation. Inhibiting these enzymes ground that aberration to a halt and greatly diminished the virus’s spread to other cells.

A ‘morning after’ spray?

Jackson and his colleagues had similar results when they incubated airway organoids with either of two other respiratory viruses—the now-surging respiratory syncytial virus and the less-common parainfluenza virus—as well as with BA.1, a variant of the omicron strain.

Omicron is more contagious, and, as expected, it infected airway-organoid multiciliated cells more quickly than the older strain used for the other SARS-CoV-2 experiments. But inhibiting viral entry or exit in airway cells still proved effective, even for this highly infectious variant.

These viral entry mechanisms may be a general property of many respiratory viruses, Jackson says.

The findings identify new targets for a nasally applied drug that, by impeding ciliary motion or microvilli gigantism, could prevent even unknown respiratory viruses—the kind you meet, say, at a pandemic—from making themselves at home in your nose or throat.

Jackson says substances used in these experiments could perhaps be optimized for use in, say, nasal sprays soon after a respiratory viral exposure, or as prophylactics.

“Delaying viral entry, exit or spread with a locally applied, short-duration drug would help our immune systems catch up and arrive in time to stop full-blown infection and hopefully limit future pandemics,” he says.

Other researchers from UCSF, the Jikei University School of Medicine in Tokyo, and the Texas Biomedical Research Institute contributed to the work.

The study had funding from the National Institutes of Health, the Stanford Diabetes Research Center, Fast Grant, the Bill and Melinda Gates Foundation, Defense Advanced Research Project Agency, the California Institute for Regenerative Medicine, Stanford Respond Innovate Scale Empower, and the Stanford Maternal and Child Health Research Institute.

Source: Stanford University

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