Culture

Wound healing in mucous tissues could ward off AIDS

image: Researchers measured changes in gene expression during SIV infection and found that activation of gene groups involved in wound healing decreased chances of progression to AIDS.

Image: 
Michael Gale, Fredrik Barrenas, Jan Komorowski et al

Wound healing events in mucous tissues during early infection by Simian Immunodeficiency Virus, or SIV, guard some primate species against developing AIDS, a recent study has learned. The research looked at why certain species can carry the virus throughout their lives, and still avoid disease progression.

SIV is closely related to the Human Immunodeficiency Virus. It is used as a laboratory model for many studies seeking AIDS and HIV cures and preventions.

Despite effective treatments to manage HIV, the virus remains a major global health threat. Approximately 37.9 million people in the world are living with an HIV infection. Each year about 770,000 people die of AIDS. As yet, there are no clinically available vaccines against HIV, or cures for the infection.

In this latest study, reported this month in Nature Communications (please see paper), scientists sought to uncover, in natural hosts, successful virus-fighting tactics that could inform the design of better antiviral drugs to treat HIV in people. They found that the biological events involved in wound healing of mucosal tissues create an environment inside the body that protects against the destructive consequences of SIV infection. (Mucosal tissues are part of the body's defense against germs.) Aspects of this wound-healing immune response could become targets for developing new therapies to prevent AIDS in people with HIV infections.

The multi-institutional study was led by Michael Gale, Jr., professor of immunology at the University of Washington School of Medicine and director of the Center for Innate Immunity and Immune Disease, and Fredrik Barrenas and Jan Komorowski of the University of Uppsala, Sweden and the Institute of Computer Sciences, Polish Academy of Sciences.

The research team combined data from their experiments and from other published studies to generate their findings.

To evaluate the virus-host interactions and immune response in the early stages of SIV and HIV infection, the researchers developed a systems biology approach - a way of representing and interpreting complex interactions - called Conserved Gene Signature Analysis. They also conducted additional types of bioinformatics analyses, which incorporate methods and tools from computer science, biology, math, statistics, information engineering and other fields.

As part of their study, the researchers compared virus host interactions and immune response to SIV, including gene expression profiles, from the African green monkey, a natural host for HIV, with those from an AIDS-susceptible species, the rhesus macaque. Similar data from human HIV infections was also evaluated.

"The use of public datasets were a key component of this research and highlights the importance of the scientific community sharing their data in public forums," Barrenas said.

The researchers explained that both HIV and SIV infect immune cells called T helper cells. These cells are abundant in the intestine and in specialized tissues elsewhere in the body. The HIV infection provokes an immune response that injures tissues surrounding the intestine. This injury allows the bacteria that normally reside in the gut to penetrate the tissue and invade other sites in the body. This causes further inflammation and damage.

The situation attracts more immune cells, some of which get infected with HIV. Others undergo a program of spontaneous cell death. Deterioration of the immune system and further decline of infection-fighting T cells can follow. If the infection progresses to AIDS, the syndrome lowers the ability to resist opportunistic pathogens and fend off cancer.

The researchers found that, in contrast, African green monkeys in the early stages of SIV infection quickly activate and maintain regenerative wound healing mechanism in their mucosal tissue. For example, in the monkeys, a white-cell mediated remodeling of tissue occurs. Some of the repair mechanisms, the researchers say, are evolutionarily conserved. One biological pathway, for instance, is roughly reminiscent of one observed in a salamander that can regenerate certain lost parts.

The green monkey's ability to activate mucous tissue wound healing, the research team found, interrupts the course of the disease such that the onset of AIDS is avoided.

"We think the regenerative wound healing process likely preserves the tissue integrity," said Gale, "and could prevent the inflammatory insults that underlie immune exhaustion, cell death and AIDS that happen due to SIV or HIV infection."

Gale added, "This maintenance of tissue integrity would be a valuable therapeutic strategy to avoid systemic immune activation and progression to AIDS. Our findings indicate that the use of therapies that stimulate the wound healing response during early infection could have a protective effect against disease from HIV infection."

Credit: 
University of Washington School of Medicine/UW Medicine

New Alzheimer risk gene discovered

A new paper in the Journal of Neuropathology & Experimental Neurology finds a gene that may help explain a large part of the genetic risk for developing Alzheimer disease.

Late-onset Alzheimer disease, the most common form of the illness, is a devastating neurological condition with aspects of heritable risk that are incompletely understood. Unfortunately, the complexity of the human genome and shortcomings of earlier research are limiting factors, so that some genetic phenomena were not surveyed completely in prior studies. For example, there are many incompletely mapped genomic regions, and areas with repetitive sequences, that could not be studied previously.

Although Alzheimer's is known to be largely heritable, a substantial proportion of the actual genetic risk for the disease has remained unexplained, despite extensive studies. This knowledge gap is known to researchers are the "missing (or hidden) heritability" problem. For example, while heritability explained 79% of late-onset Alzheimer disease risk in a Swedish twin study, common risk variants identified by pervious genetic studies explained only 20% to 50% of late-onset Alzheimer disease. In other words, a relatively large amount of genetic influence on late-onset Alzheimer disease risk was not explained by prior genetic studies.

Recent advances in sequencing technologies have enabled more comprehensive studies. Such developments allow for more precise and accurate identification of genetic material than was available in earlier gene variant studies.

In the present study, researchers analyzed Alzheimer's Disease Sequencing Project data derived from over 10,000 people (research volunteers who agreed to have their genetic data evaluated in combination with their disease status), with the goal of identifying genetic variation associated with late-onset Alzheimer disease.

Preliminary results found evidence of late-onset Alzheimer disease -linked genetic variation within a segment of a gene called Mucin 6. Although the underlying mechanisms are mostly still unknown, researchers here believe that it's possible to draw credible and testable hypotheses based on these results. For example, the genetic variant that was associated with Alzheimer's disease risk may implicate a biochemical pathway in the brain that then represents a potential therapeutic target, a topic for future studies.

Corresponding authors were Yuriko Katsumata and Peter Nelson, both from the University of Kentucky. Dr. Nelson said of this study, "Our findings were made in a group of patients that is relatively small for a genetics study--some recent studies included hundreds of thousands of research subjects! That small sample size means two things: first, we should exercise caution and we need to make sure the phenomenon can be replicated in other groups; and second, it implies that there is a very large effect size--the genetic variation is strongly associated with the disease."

Credit: 
Oxford University Press USA

New type of e-cigarette vaping injury described in CMAJ

A research case report describing lung injury related to e-cigarette use in a 17-year-old Canadian may be the first documented case of a new form of damage from vaping products. The article, published in CMAJ (Canadian Medical Association Journal) provides new evidence on forms of lung injury that can result from vaping.

Recently, several cases of "e-cigarette or vaping product use-associated lung injury" (EVALI) have been described. However, this patient presented with a new type of vaping-related injury that is similar to "popcorn lung," a condition seen in workers exposed to the chemical flavouring diacetyl, an ingredient used in microwave popcorn. If inhaled, the chemical causes bronchiolitis, which is characterized by the small airways of the lungs becoming inflamed and obstructed.

A team of authors from Lawson Health Research Institute in London, Ontario, and University Health Network (UHN) in Toronto, who were all involved in the care of the patient, report on the case of life-threatening bronchiolitis. The article describes a previously healthy 17-year-old male who initially presented for care after a week of persistent and intractable cough and was eventually hospitalized and put on life support. After ruling out other causes, the authors suspected flavoured e-liquids as the cause. The youth's family reported that he vaped daily using a variety of flavoured cartridges and used tetrahydrocannabinol (THC) regularly.

"This novel disease pattern of airway injury associated with vaping leading to chronic obstruction appears to be distinct from the alveolar injury characterizing the EVALI cases recently reported in the US, and the 7 confirmed or probable cases in Canada, highlighting the need for further research and regulation of e-cigarettes," writes lead author Dr. Karen Bosma, Associate Scientist at Lawson and Intensivist at London Health Sciences Centre (LHSC).

The CMAJ case study provides detailed medical information on the extent and type of injury as well as treatment, although the Middlesex-London Health Unit reported on the youth's condition earlier this fall to extend an early warning of the risks of vaping.

"This case of life-threatening acute bronchiolitis posed a diagnostic and therapeutic challenge," write the authors. "Given the patient's intense vaping exposure to flavoured e-liquid and negative workup for other causes of bronchiolitis, we suspected that bronchiolitis obliterans might have been developing in this patient as in microwave popcorn factory workers exposed to occupational inhalation of diacetyl."

The authors referred the patient to a lung transplant centre for further evaluation and reported the case to authorities (Government of Canada's consumer product incident report system) as an adverse reaction to a consumer product, e-cigarettes. They also alerted Health Canada for further investigation.

The youth narrowly avoided the need for a double lung transplant, but now has evidence of chronic damage to his airways. He is still recovering from his lengthy stay in the intensive care unit, and is abstaining from e-cigarettes, marijuana and tobacco.

Emerging reports indicate that e-cigarettes are causing a variety of lung illnesses and injuries. According to a 2017 report, e-cigarettes are the most commonly used nicotine products among Canadian youth, with an estimated 272,000 Canadians aged 15 to 24 years reporting e-cigarette use within the last 30 days.

"This case may represent the first direct evidence of the lung disease most expected to result from e-cigarette use," writes Dr. Matthew Stanbrook, Deputy Editor, CMAJ, in a linked editorial.

Stanbrook urges the federal government to ban these harmful substances and ignore the fear-mongering from the tobacco industry that people will revert to smoking cigarettes.

"From the start, CMAJ has called for a ban on flavourings in e-liquids, restrictions on e-cigarette advertising equivalent to those for tobacco products, and an effective standard for quality and safety to be imposed on every e-cigarette product sold. We do so again now," Dr. Stanbrook writes.

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Canadian Medical Association Journal

American University researchers sequence genome of the 'devil worm'

image: H. Mephisto (the Devil Worm). (microscopic image, magnified 200x)

Image: 
Prof. John Bracht, American University

When scientists discovered a worm deep in an aquifer nearly one mile underground, they hailed it as the discovery of the deepest-living animal ever found. Now American University researchers, reporting in Nature Communications, have sequenced the genome of the unique animal, referred to as the 'Devil Worm' for its ability to survive in harsh, subsurface conditions. The Devil Worm's genome provides clues to how an organism adapts to lethal environmental conditions. Future research into how it evolved could help humans learn lessons for how to adapt to a warming climate.

In 2008, Gaetan Borgonie from the University of Ghent and Princeton University geoscientist Tullis Onstott discovered the microscopic Devil Worm while investigating subterrestrial bacterial communities in active gold mines in South Africa. Borgonie and his team were stunned to discover the worm, a complex, multi-cellular animal thriving in an environment thought only livable for microbes, with high temperatures, little oxygen and high amounts of methane.

Researchers named the worm Halicephalobus mephisto, in honor of Mephistopheles, a subterranean demon from the medieval German legend Faust.

Evolutionary adaptation to heat

The Devil Worm is the first subterrestrial animal to have its genome sequenced. The genome offers evidence of how life can exist below Earth's surface and opens up a new way of understanding how life can survive beyond Earth, said John Bracht, assistant professor of biology at American University who led the genome sequencing project.

The sequencing revealed that the genome encodes an unusually large number of heat-shock proteins known as Hsp70, which is notable because many nematode species whose genomes are sequenced do not reveal such a large number. Hsp70 is a well-studied gene that exists in all life forms and restores cellular health due to heat damage.

Many of the Hsp70 genes in the Devil Worm's genome were copies of themselves. The genome also has extra copies of AIG1 genes, known cellular survival genes in plants and animals. More research will be needed, but Bracht believes the presence of copies of the gene signifies the worm's evolutionary adaptation.

"The Devil Worm can't run away; it's underground," Bracht explained. "It has no choice but to adapt or die. We propose that when an animal cannot escape intense heat, it starts making additional copies of these two genes to survive."

By scanning other genomes, Bracht identified other cases where the same two gene families, Hsp70 and AIG1, are expanded. The animals he identified are bivalves, a group of mollusks including clams, oysters and mussels. They are heat-adapted like the Devil Worm. This suggests that the pattern identified in the Devil Worm may extend more generally to organisms unable to escape environmental heat. This work was also recently published in the Journal of Molecular Evolution with an AU Biology undergraduate first author, Megan Guerin.

'The aliens have landed at AU'

Bracht got the chance to sequence the unique worm's genome as a post-doctoral fellow at Princeton University. He carried the project over to American University when he joined the biology faculty in 2014. Two biology master's students working in his lab, Deborah Weinstein and Sarah Allen, contributed research and writing of the Nature Communications paper and are first and second authors, respectively, on the manuscript. Kathryn Walters-Conte, Ph.D., director of AU’s Master’s in Biotechnology program, also contributed to the paper.

Nearly a decade ago, the Devil Worm was unknown and living below the Earth's surface. Now it's a subject of study in science laboratories, including Bracht's. When Bracht brought Devil Worms from a laboratory in South Africa that cultures them to his laboratory at AU, he recalls saying to his students that aliens landed at AU. The metaphor isn't a stretch. NASA supports research of the Devil Worm for what it can teach scientists about the search for life beyond Earth.

"Part of this work entails looking for 'biosignatures' of life--stable chemical clues left behind by living things. We focus on a ubiquitous biosignature of organic life--genomic DNA--obtained from an animal that has adapted to an environment once considered uninhabitable to complex life: the deep terrestrial subsurface," Bracht said. "It is work that might prompt us to broaden the search for extraterrestrial life to 'uninhabitable' exoplanets' deep subterrestrial regions."

Nematodes are well suited to studies of evolutionary adaptation, Bracht said. They have adapted to a diverse set of environments and are among the most abundant animals on earth. Future work involving the Devil Worm in Bracht's lab will pinpoint Hsp70's function, such as inactivating the gene to test its response to heat stress. Other work could involve gene-transfer studies in C.elegans, a type of heat-intolerant microscopic roundworm, to see if it becomes heat-resilient.

Credit: 
American University

Excellent mental health for 2/3 of Indigenous people off reserve

Two-thirds (68%) of Indigenous people living off reserve in Canada have excellent mental health, according to a nationally representative study conducted by the University of Toronto and Algoma University.

"These findings underline the incredible strength and resiliency of Indigenous people. Most previous research has focused solely on deficits. In contrast, our findings show that despite stark economic inequalities and a history of residential schools, the majority of Indigenous people are free of addictions, suicidal thoughts and mental illness," according to co-author Rose Cameron who is an Anishinaabekwe elder and an Associate Professor and Director of the Social Work program at Algoma University in Sault Ste. Marie, Canada. "However, we know that there is still an urgent need to address poverty and support those who are struggling in order to bring the community up to parity with the wider Canadian population," in which 73.5% reported excellent mental health.

"Supportive social connections are a key to well-being; Among our Indigenous respondents, those with at least one person who provided them with a sense of emotional security and well-being were much more likely to be in excellent mental health than those without a confidant [70% vs 29%]," reported co-author Siwon Lee, a recent Master of Public Health graduate of the University of Toronto. "Interventions are needed to promote social support and to decrease social isolation and loneliness."

"Poverty was a serious impediment to mental well-being. Only 53% of Indigenous respondents whose income was in the bottom 10% had complete mental health compared to 73% of those whose income was above the Canadian average," reported lead author Esme Fuller-Thomson, Professor at the University of Toronto's Factor-Inwentash Faculty of Social Work and Director of the Institute for Life Course & Aging. "As a nation, we need a concerted effort to improve the financial situation of our most economically disadvantaged population."

"Our study found that those with post-secondary degrees were more likely to be in excellent mental health compared to their counterparts with less education. Education opens doors to better careers, higher income, better access to mental-health care and more opportunities in life. Currently, many isolated reserves do not have local high schools, which forces children as young as 14 to leave their family, home and community and move to larger towns and cities in order to study. These inequities need to be addressed if we hope to improve the high-school graduation rate of Indigenous youth in Canada," said co-author Senyo Agbeyaka, a Masters of Social Work graduate of the University of Toronto.

"This study concluded that Indigenous men were much more likely than women to be in excellent mental health. Some of the excess vulnerability is due to the fact that women had experienced more childhood adversities and chronic pain, which makes it difficult to experience mental flourishing." reported co-author Philip Baiden, a PhD graduate of the FIFSW who is now an Assistant Professor at the University of Texas at Arlington.

The definition of excellent mental health in this study had three components: 1) Respondents must report daily or almost daily happiness or life satisfaction in the past month; 2) They must report social and psychological wellbeing on an almost daily basis in the past month, and: 3) They had to be free of all mental illness, serious suicidal thoughts and substance dependence in the preceding year.

"For those who are experiencing mental-health problems, culturally adapted cognitive behavioural therapy [CBT] is a very promising intervention. It has been shown to be extremely effective in treating psychological distress among Indigenous individuals around the world," said co-author Talib M. Karamally, a recent Master of Industrial Relations and Human Resources graduate at the University of Toronto.

"In sum, there are multiple factors that are associated with optimal mental health among Indigenous people, in particular, having a university degree, social support and being free of chronic pain and insomnia. While it is encouraging that the prevalence of excellent mental health is quite high, there are many policy changes that could hasten better outcomes for Aboriginal peoples who are vulnerable." Cameron said.

Credit: 
University of Toronto

Cybershoppers make better buying decisions on PCs than phones -- Ben-Gurion U. researchers

BEER-SHEVA, Israel...November 21, 2019 - This holiday shopping season, consumers may make better shopping decisions using their PCs rather than smart phones or other mobile devices, according to new research from Ben-Gurion University of the Negev.

"The issue is not actually screen size," says Prof. Lior Fink, head of the Mobile Behavior Lab and a member of the BGU Department of Industrial Engineering and Management. "It is actually the fact that sites adjusted for mobile viewing reduce the information offered on the results page and require more digging around in the site for information. Sites adjusted for PC viewing give more information right up front."

This is the first study that differentiates between screen size and information reduction, which are often mixed up. The findings will be presented next month at the International Conference on Information Systems, the top academic conference in the field.

In 2018, phones accounted for 47% of traffic to online stores and 36% of sales according to Adobe Analytics. Last Black Friday was the first during which there were more than $2 billion in online U.S. sales via phones.

"Most e-commerce providers use 'responsive web design' to adapt the presentation of information to the device used." Fink explains. "While mobile friendly presentation improves visibility, it reduces the amount of information and causes consumers to make decisions that are less consistent with their preferences."

From a pure decision-making perspective, the study shows it is better to simply present the same information irrespective of the device used. Consumers will find the information more difficult to view on mobile devices, but their decisions will be more accurate.

Prof. Fink and his master's student Daniele Papismedov conducted two experiments in the Mobile Behavior Lab focused on choosing a fictitious hotel room among 11 room options. Participants viewed the information either on a PC or on a mobile device. They viewed eight informational features about each room option on the PC display and only three on a mobile display. While all the information was available in both displays, it was more readily available on the PC display. The assignments to a specific device and to a specific display were independent of each other.

The experiments showed that when the same information was presented on both screens right up front, equally accurate decisions were made. As a result, the research showed that participants made decisions that were less accurate and less aligned with their preferences as a consequence of the mobile display but not as a consequence of the mobile device.

Whether it is selecting a hotel room, a new outfit or a new television, the researchers believe that shoppers will have a more accurate shopping experience in line with their preferences using a PC rather than a mobile friendly format.

Credit: 
American Associates, Ben-Gurion University of the Negev

Menopause isn't the only reason for low libido in older women

PITTSBURGH, Nov. 20, 2019 - A qualitative study by researchers at the University of Pittsburgh School of Medicine found that women in their 60s report various reasons behind why they lack libido.

The study, published today in Menopause, distilled interviews with dozens of women about their lack of desire for sex into several major themes -- including sexual dysfunction in their partners.

"If a woman is having sexual problems, what's going on with her partner may be contributing. Sex doesn't occur in a vacuum," said lead author Holly Thomas, M.D., M.S., assistant professor of medicine at Pitt.

Up to 40% of women over age 60 have low libido, and about 10% of them report feeling bothered by it.

To understand what's causing these women to have lower libido than they'd like, Thomas and her team conducted three 12-woman focus groups and interviewed 15 other women privately, depending on which setting the participant preferred.

Through these conversations, five major themes emerged:

Postmenopausal vaginal symptoms.

Erectile dysfunction in partner.

Fatigue or bodily pain.

Life stressors.

Body image.

The most surprising thread here, Thomas said, was that so many women identified sexual dysfunction in their male partners as a major contributor to their own lack of desire for sex.

"Some women find workarounds, but others get stonewalled by their partner because he feels defensive," Thomas said. "As women we're encouraged to be accommodating, so we learn to tamp down our own needs and desires, and prioritize those of others."

Another revelation was that for some women, despite having retired from their jobs and successfully ejected their adult children from their houses, they were still too stressed to view sex as a priority.

For instance, one woman bemoaned the emotional burden of caring for her ailing mother while simultaneously supporting her daughter through recovery from a substance use disorder.

There were several limitations of this study, most notably the small, racially homogeneous sample and the lack of quantitative data.

Still, since most of the research on low libido in older women has focused on hormones, Thomas said, hearing detailed accounts from the women themselves produces novel ideas that may not come out of a large survey.

Credit: 
University of Pittsburgh

Estimating the environmental impact of Bitcoin mining

As an alternative to government-issued money, the cryptocurrency Bitcoin offers relative anonymity, no sales tax and freedom from bank and government interference. But some people argue that these benefits have an enormous environmental impact, particularly with regard to Bitcoin mining -- the process used to secure the cryptocurrency. Now, researchers reporting in ACS' Environmental Science & Technology have estimated that past and future environmental impacts of Bitcoin mining could be lower than previously thought.

In contrast to traditional banks, which keep records of balances and transactions at a centralized location, in Bitcoin all transactions are stored digitally as "blocks" in a chain that is kept by a network of peers. Using special computers, Bitcoin miners in this network compete to solve a mathematical puzzle. The winner, who earns the right to add the next block of data to the chain, is rewarded with new Bitcoin currency. This mining requires substantial electricity to power the special computers, but current estimates of the impact associated with this energy use suffer from a lack of accurate data. Susanne Köhler and Massimo Pizzol wanted to conduct a life cycle assessment to better understand the total environmental impact of Bitcoin mining.

The researchers estimated the electricity consumption and carbon dioxide emissions in 2018 for each stage of Bitcoin mining, from the extraction of raw materials to make the equipment to its production, use and recycling. They calculated that the Bitcoin network consumed 31.3 Terawatt-hours of electricity and generated 17.3 megatons of carbon dioxide equivalents in 2018, which were lower than previous estimates. About 99% of the environmental impact came from the use of the mining equipment, with minimal contributions from production and recycling. The location of the miners had the largest impact on the environment, with areas that use mostly fossil fuels for electricity, such as Inner Mongolia, China, contributing more to the carbon footprint than regions using renewable resources, such as Sichuan, China. The analysis also predicted that the environmental impact per miner will shrink if mining equipment becomes more efficient, use of renewable energy sources increases, or miners relocate to cooler climates, where less energy is needed to cool the computers. However, the overall number of miners is likely to continue increasing, at least in the short term, the researchers say.

Credit: 
American Chemical Society

UK Study: Lack of economic support hinders cognitive abilities of children of single mothers

Over the last 60 years, the percentage of children in the United Kingdom living in homes headed by a single mother has risen steadily. A new study examined how the impact of single motherhood on children's verbal cognitive abilities has changed and how the age of children when their parents separate affects those abilities. The study concluded that children who lived with a single mother before age 11 had lower verbal cognitive ability even after considering mothers' education and their age at the time of the child's birth.

The study was done by researchers at the University of Bristol, Universidad de Alcalá, and the University of Bath. It is published in Child Development, a journal of the Society for Research in Child Development.

"Our study shows that almost all of the relationships between single motherhood and negative consequences for children's cognitive attainment can be explained by families' reduced economic circumstances," explains Susan Harkness, professor of public policy at the University of Bristol, who led the study. "Although single motherhood has become much more common in the U.K., deficits associated with parenting--as opposed to reduced economic circumstances--have all but disappeared over the last 40 years."

Researchers used data from three large, nationally representative studies of British children born in 1958, 1970, and 2000; each study included more than 10,000 children and measured children's verbal ability on standardized tests at age 10 (1970 study) or 11 (1958 and 2000 studies). The studies also collected information on economic and family characteristics, as well as family members' health and well-being.

Prior studies, which used data from children born in the 1940s to the 1970s, compared children of single mothers with children in families that are otherwise similar but not headed by a single mother, so the indirect effect of single motherhood on children's outcomes is not well understood. In this study, researchers sought to determine how the family environment is affected by single motherhood, specifically, to what extent the economic and parenting resources of children in single- and two-parent families differ. They then assessed how children in single-mother families might have done had their parents not separated, and how economic resources and differences in parenting affected children's attainment.

The study examined how being born to a single mother, having parents separate after birth but before age 7, and having parents separate between ages 7 and 11 affected children's verbal ability at age 11. It also assessed how single motherhood affected economic resources and parenting, and the impact that this in turn had on children's verbal ability. Children's cognitive ability is strongly related to a range of later life outcomes, including the likelihood of dropping out of school, earnings, occupational attainment, crime, substance abuse, and mental health.

The study found that:

Children who lived with a single mother before age 11 had lower verbal cognitive attainment than children whose parents stayed together.

For children born in 2000, the age at which their parents separated mattered to their attainment: Those whose parents separated before they were 7 had less optimal cognitive outcomes than those whose parents separated when they were between 7 and 11; the study saw no statistically significant effects for the latter group. This pattern differs from that of children born in 1958 or 1970; for these children, the age at which their parents separated had little effect on their attainment.

Few differences were identified in the parenting behavior of single- and two-parent families, and this contributed little to the observed differences in attainment, leading the researchers to conclude that lower attainment is largely due to single-mother families' lower economic resources.

"Overall, our findings suggest two policy responses in the U.K.: supporting the incomes of single-parent families, particularly those with very young children, and addressing the growing gap in attainment between all children whose parents have adverse economic characteristics, whether partnered or not," said Paul Gregg, professor of public policy at the University of Bath, who coauthored the study.

Credit: 
Society for Research in Child Development

Emissions from electricity generation lead to premature deaths for some racial groups

image: University of Washington researchers have found that air pollution from electricity generation emissions in 2014 led to about 16,000 premature deaths in the continental U.S. In many states, the majority of the health impacts came from emissions originating in other states. Shown here is a map of the U.S. where the states are colored according to the number of premature deaths per 100,000 people in that state. Darker colors represent more deaths. For an interactive version of this map, please visit: https://public.tableau.com/views/air-pollution-deaths-electricity/Dashbo...

Image: 
Rebecca Gourley/ University of Washington

Air pollution doesn't just come from cars on the road, generating electricity from fossil fuels also releases fine particulate matter into the air.

In general, fine particulate matter can lead to heart attacks, strokes, lung cancer and other diseases, and is responsible for more than 100,000 deaths each year in the United States.

Now University of Washington researchers have found that air pollution from electricity generation emissions in 2014 led to about 16,000 premature deaths in the continental U.S. In many states, the majority of the health impacts came from emissions originating in other states. The team also found that exposures were higher for black and white non-Latino Americans than for other groups, and that this disparity held even after accounting for differences in income.

The researchers published their results Nov. 20 in the journal Environmental Science & Technology.

"Our data show that even if states take measures to change their own electricity production methods, what happens across state lines could dramatically affect their population," said senior author Julian Marshall, a UW professor of civil and environmental engineering.

The team first examined how emissions from electricity generation plants could move across the continental U.S.

"We looked at emissions from different types of power plants -- including coal, natural gas, diesel and oil power plants -- and modeled how the pollutants would travel based on things like wind patterns or rain. We also consider how emissions can react in the atmosphere to form fine particle air pollution," said lead author Maninder Thind, a UW civil and environmental engineering doctoral student. "That gave us a map of pollution concentrations across the country. Then we overlaid that map with data from the census to get an estimate of where people live and how this pollution results in health impacts."

Then, using mortality data from the National Center for Health Statistics, the team estimated premature deaths due to electricity generation emissions. In 2014, there were about 16,000 premature deaths. The researchers estimate that 91% of premature deaths were the result of emissions from coal-fired power plants. The number of deaths in each state varied, with Pennsylvania having the highest number -- about 2,000 -- and Montana and Idaho having the lowest number, with fewer than 10 deaths each.

Emissions from electricity generation don't stop at state lines -- many states "imported" or "exported" pollution. In 36 states, more than half of premature deaths were the result of emissions from other states.

Overall, the team found that emissions affected black Americans the most, leading to about seven premature deaths per 100,000 people in that group. White non-Latino Americans were the second most affected group with about six premature deaths per 100,000 people. Other groups averaged about four premature deaths per 100,000 people.

"A lot of people may expect that the disparity we see for race or ethnicity comes from an underlying difference in income. But that's not what we see," said co-author Christopher Tessum, a research scientist in the UW's civil and environmental engineering department. "We find that differences by race or ethnicity tend to be larger than differences by income group."

While the researchers found that overall, lower-income households experienced more exposure to emissions, the disparities they saw between race groups still held when they accounted for income.

The amount of power plant pollution that people breathe can vary by where they live. These disparities may be influenced by societal trends. For example, where people live often reflects segregation or other conditions from decades earlier.

These trends don't always hold when looking at individual areas. For example, exposures for Native Americans are lower than other groups overall, but in Kansas and Oklahoma, this group is the most exposed. The state with the largest disparities by race is Kentucky, where black people are the most exposed.

"We've seen in our previous research that our society is more segregated by race than by income, and now it's showing up again with air pollution from electricity generation emissions," Marshall said. "These results can help local, state or national governments make more informed decisions that will improve everyone's air quality and quality of life."

Inês Azevedo, a professor of energy resources engineering at Stanford University, is also a co-author on this paper. This publication was developed as part of the Center for Air, Climate, and Energy Solutions, which was supported under an Assistance Agreement awarded by the U.S. Environmental Protection Agency.

Credit: 
University of Washington

Mount Sinai researchers uncover new molecular drivers of Parkinson's disease

Scientists at the Icahn School of Medicine at Mount Sinai have uncovered new molecular drivers of Parkinson's disease using a sophisticated statistical technique called multiscale gene network analysis (MGNA). The team was also able to determine how these molecular drivers impact the functions of genes involved in the disease. The results, which may point to potential new treatments, were published today in Nature Communications.

Some cases of Parkinson's are directly caused by genetic mutations, but these cases are rare. Approximately 80 percent of cases have no known cause, and though there are some genes that may slightly increase an individual's risk of developing the disease, the biological impacts of these genes remain unclear.

"This study offers a novel approach to understanding the majority of cases of Parkinson's," said Bin Zhang, PhD, Professor of Genetics and Genomic Sciences at the Icahn Institute for Data Science and Genomic Technology and Director of the Mount Sinai Center for Transformative Disease Modeling at the Icahn School of Medicine at Mount Sinai. "The strategy not only reveals new drivers, but it also elucidates the functional context of the known Parkinson's disease risk factor genes."

Dr. Zhang and his team originally developed the MGNA method to research the molecular mechanisms of Alzheimer's disease. Since that study was published about six years ago, they have significantly improved the technique through funding from the National Institutes of Health (NIH)/National Institute on Aging (NIA) Accelerating Medicines Partnership - Alzheimer's Disease (https://www.nia.nih.gov/research/amp-ad) (AMP-AD) program and have applied it to a variety of complex diseases from Alzheimer's to cancer. The strategy takes into account genetic, epigenetic, transcriptomic, pathological, and clinical data from a large pool of tissue samples and identifies links between them.

"This multiscale network analysis approach is a powerful way to dissect the molecular mechanisms of complex diseases like Alzheimer's," said Suzana Petanceska, PhD, program director of the AMP-AD Target Discovery program at the NIA, which co-funded the study. "It is exciting to see that AMP-AD can provide new mechanistic insights to Parkinson's disease that could lead to new therapeutic opportunities."

Unfortunately, there are no gene expression data sets based on a sufficiently large number of informative brain samples from Parkinson's patients for the powerful MGNA to be effective. Instead, the researchers combined data from eight different studies that included postmortem analyses of the substantia nigra--the part of the brain most affected by Parkinson's disease. This gave the team a larger dataset from a total of 83 patients, which they then compared to 70 controls who did not have Parkinson's.

Applying MGNA to the combined data set, the scientists identified a number of key regulators of the gene networks that had never before been associated with the disease.

Next, they teamed up with Zhenyu Yue, PhD, Professor of Neurology and Neuroscience at the Icahn School of Medicine and the Director of Basic and Translational Research in Movement Disorders, whose work is supported by NIH Udall Centers of Excellence for Parkinson's Disease Research, to experimentally validate the findings in mice. They chose to test the effects of STMN2, a gene that the analysis identified as a key regulator of the Parkinson's molecular network. The gene is normally expressed in neurons that produce dopamine, a neurotransmitter that is depleted in the substantia nigra of Parkinson's patients.

To test its influence on Parkinson's disease, Dr. Yue and his team knocked down the STMN2 gene in the substantia nigra of the mice. RNA sequencing showed that reduction of STMN2 led to upregulation of nine genes that had previously been associated with the disease. The mice developed Parkinson's-like pathologies such as degeneration of dopaminergic neurons in the substantia nigra and an increase in the concentration of the toxic, modified α-synuclein protein, both of which are considered hallmarks of the disease. Additionally, the mice struggled with motor tasks such as maintaining balance on a rod, indicative of the disruption of their motor function control.

Despite the fact that the team was able to create a large enough sample size to apply the multiscale network analysis, the researchers emphasized that 83 patients is still a relatively small number and the results should be validated in larger studies. Still, "The work opens up a new avenue for studying the disease," said Dr. Yue. "The new genes we identified suggest that new pathways should be considered as potential targets for drug development, particularly for idiopathic Parkinson's cases."

Credit: 
The Mount Sinai Hospital / Mount Sinai School of Medicine

The ever-changing brain: Shining a light on synaptic plasticity

image: In the membrane outside the synapse, the AMPA receptor subunit concentrations are low; subunits mainly exist as individuals or form pairs. Within the synapse, the AMPA receptor subunit concentrations are high, and tetramers form. Tetramers lifetimes are about 0.2 seconds.

Image: 
OIST

Synapses - specialized structures in neurons - allow these nerve cells to communicate with one another. In the synapse, one neuron emits chemical messengers called neurotransmitters, and an apposed neuron receives them using tiny structures called receptors.

A specific type of receptor, the AMPA receptor, plays a crucial role in learning and memory processes. However, scientists don't yet fully understand how these AMPA receptors form and work.

Now, researchers in the Membrane Cooperativity Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) in Japan, in collaboration with researchers from universities across Japan, have found that AMPA receptors form and disintegrate continually, within a fraction of a second, rather than existing as stable entities. The scientists' findings, published in Nature Communications, may help clarify early stages of synaptic plasticity: neural activity that is key for learning and memory. The research may also have pharmacological applications in the treatment of epilepsy.

The changing brain

AMPA receptors are composed of four molecules, or subunits - called GluA1, 2, 3, and 4 - which unite to form structures called tetramers. Different combinations of the subunits form the tetramers; this means there are 256 possible configurations of AMPA receptor.

Scientists have long believed that these tetramers originate in the endoplasmic reticulum, the cell's "manufacturing center," before migrating to the synapses, all while retaining stable structures for hours or even days.

"This tetramer stability could actually be problematic for neurons," said Professor Akihiro Kusumi, a co-author of the study. "The synapses need AMPA receptor tetramers with different combinations of subunits as the brain learns and its neuronal circuits change. Thus, we had a gut feeling that something was terribly wrong with the accepted notion of how AMPA receptors form, migrate, and work."

Looking at AMPA receptors in motion at single-molecule resolutions

Following this intuition, the researchers put fluorescent tags on each individual subunit molecule of the AMPA receptors. Then, they tracked the molecules' movements in live cells at nanometer-precisions. They used a single-molecule fluorescence microscope and software to analyze the motion of the single molecules, a method Kusumi and his colleagues pioneered.

By studying how the AMPA receptor molecules jostled around in the membrane and bound to each other, the researchers found that the AMPA receptor subunits existed as single molecules as well as assemblies two, three, and four molecules.

Tetramers were found, but they fell apart in about 0.1 to 0.2 seconds. Then, however, the separated molecules found other partner molecules to form new assemblies of two, three, and four molecules again, continually repeating this process.

In addition, the researchers found that when the molecules formed tetramers, albeit briefly, they worked as tiny channels that opened for less than 0.1 seconds.

Since the functional tetramers are continually broken up to form new tetramers, AMPA receptor tetramers with different subunit compositions can readily be formed. This represents a novel mechanism for synaptic plasticity.

Kusumi noted that the team's findings may have medical applications. Individuals with epilepsy have an excess of glutamate, the neurotransmitter that binds to AMPA receptors in the brain. These individuals are often treated with anticonvulsants that stop glutamate from binding to AMPA receptor tetramers, but these treatments can be too overpowering, and therefore ineffective.

Kusumi believes the development of drugs that slow down the formation of tetramers with certain subunit compositions in the brain could mitigate problematic types of synaptic plasticity, thus diminishing the symptoms of epilepsy.

Credit: 
Okinawa Institute of Science and Technology (OIST) Graduate University

Skipping breakfast linked to lower GCSE grades

Students who rarely ate breakfast on school days achieved lower GCSE grades than those who ate breakfast frequently, according to a new study in Yorkshire.

Researchers, from the University of Leeds, have for the first time demonstrated a link between eating breakfast and GCSE performance for secondary school students in the UK.

Adding together all of a student's exam results, they found that students who said they rarely ate breakfast achieved nearly two grades lower than those who rarely missed their morning meal.

The research is published today in the journal Frontiers in Public Health.

Lead researcher Dr Katie Adolphus, from the University of Leeds' School of Psychology, said: "Our study suggests that secondary school students are at a disadvantage if they are not getting a morning meal to fuel their brains for the start of the school day.

"The UK has a growing problem of food poverty, with an estimated half a million children arriving at school each day too hungry to learn. Previously we have shown that eating breakfast has a positive impact on children's cognition.

"This research suggests that poor nutrition is associated with worse results at school."

The Government in England run a national, means-tested free school lunch programme accessible to all students, but there is no equivalent for breakfast.
Charities Magic Breakfast and Family Action deliver a breakfast programme funded by the Department for Education, which provides free breakfasts for more than 1,800 schools located in the most socio-economically deprived parts of England.

Separately, Magic Breakfast supports breakfast provision in a further 480 UK schools. However, this leaves many of the 24,000 state-funded schools in England without free breakfast provision for children not getting breakfast at home.

Some schools compensate by offering breakfast clubs they have to fund themselves, or funded by companies such as Kellogg's.

The Leeds researchers say their findings support the calls to expand the current limited free school breakfast programme to include every state school in England. A policy proposal from Magic Breakfast to introduce school breakfast legislation is currently being considered by politicians, which has been supported by Leeds academics.

Alex Cunningham, CEO of Magic Breakfast, said: "This study is a valuable insight, reinforcing the importance of breakfast in boosting pupils' academic attainment and removing barriers to learning. Education is crucial to a child's future life success and escaping poverty, therefore ensuring every child has access to a healthy start to the day must be a priority.

"We are grateful to the University of Leeds for highlighting this positive impact and welcome their findings, highlighting once again the importance of our work with schools."
GCSE performance

The researchers surveyed 294 students from schools and colleges in West Yorkshire in 2011, and found that 29% rarely or never ate breakfast on school days, whilst 18% ate breakfast occasionally, and 53% frequently. Their figures are similar to the latest national data for England in 2019, which found that more than 16% of secondary school children miss breakfast.

GCSE grades were converted to point scores using the Department for Education's 2012 system, where A* = 58, A = 52, B = 46, and so on. Adding up students' scores across all subjects gave students an aggregated score.

Those who rarely ate breakfast scored on average 10.25 points lower than those who frequently ate breakfast, a difference of nearly two grades, after accounting for other important factors including socio-economic status, ethnicity, age, sex and BMI.

Looking at performance for each individual GCSE, they found that students who rarely ate breakfast scored on average 1.20 points lower than those who frequently ate breakfast, after accounting for other factors. Each grade equates to six points, so the difference accounted for a drop of a fifth of a grade for every GCSE an individual achieved.

Nicola Dolton, Programme Manager for the National School Breakfast Programme, from Family Action, said: "The National School Breakfast Programme is delighted to see the publication of this thorough and compelling research, highlighting the impact that breakfast consumption has on a child's GCSE attainment.

"This report provides impressive evidence that eating a healthy breakfast improves a child's educational attainment, which supports our own findings of improvements in a child's concentration in class, readiness to learn, behaviour and punctuality."

Credit: 
University of Leeds

A decade after the predators have gone, Galapagos Island finches are still being spooked

image: Pictured here: Geospiza fuliginosa

Image: 
Kiyoko Gotanda

On some of the Galapagos Islands where human-introduced predators of Darwin's finches were eradicated over a decade ago, the finches are still acting as though they are in danger, according to research published today in the Journal of Animal Ecology.

The study found that the finches' fearful responses - known as antipredator behaviour - were sustained through multiple generations after the threat was gone, which could have detrimental consequences for their survival.

The work by Dr Kiyoko Gotanda, a zoologist at the University of Cambridge, is one of the first studies to look at behavioural adaptations in a species following the eradication of invasive predators. The research focused on one species of Darwin's iconic finches - the small ground finch, Geospiza fuliginosa. Given their estimated life span, today's finches are not likely to be the same birds that had originally developed the response to defend themselves from predators.

"These surprising results suggest that whatever influences this fearful behaviour is more complicated than just the presence or absence of invasive predators," said Gotanda, sole author of the paper.

The Galapagos Islands provide a natural stage to compare different predator situations. Some islands have never had invasive predators, others currently have predators like domestic cats and rats that arrived with humans, while others have had these predators in the past and they have now been eradicated.

Gotanda found that finches on islands with predators were wary, and flew away from an approaching researcher - imitating an approaching predator - at a much greater distance than the finches on pristine islands without predators. This increased antipredator behaviour has been maintained on islands where invasive predators have been successfully eradicated, even though eradication happened eight and thirteen years earlier.

"While the mechanism for the transmission of the fearful behaviour through the generations requires further study, this sustained response has consequences for evaluating conservation efforts," said Gotanda. "The time and energy finches spend spooking themselves by fleeing when they are not in danger could be better spent looking for food, mating, laying eggs, and rearing their young."

Conservation management of species of concern on islands often involves getting rid of invasive predators. Understanding how species adapt their behaviour once predators have been eradicated - and how quickly this occurs - could better inform efforts to support the recovery of a target species. Understanding the effects of human influence such as the introduction of invasive predators could help predict how species respond to rapidly changing environments.

Gotanda also looked at the effect of urbanisation on finch behaviour and found - as is generally seen in towns and cities - the birds were less fearful as they became used to the presence of humans. On some islands the urban finches were even bolder than those on islands that had never seen invasive predators at all. This could make them vulnerable to threats like invasive predators, which are present in urban areas on the Galapagos. This suggests that the effects of urbanisation on species are strong enough to counteract adaptations to other human influences such as invasive predators.

When Charles Darwin visited the Galapagos Islands during his Voyage of the Beagle in 1835, he could famously get close enough to throw his hat over the birds. The animals were so unused to humans that they did not see Darwin - a potential predator - as a threat. Since then, the arrival of both humans and invasive predators such as cats and rats on many of the islands drove the birds to develop fear, and fly away at the sight of danger. Subsequent eradication efforts have been necessary to protect the iconic finches.

Credit: 
University of Cambridge

Leadership's in the blood for tiny fish

image: Guppy

Image: 
Darren Croft

Leadership during cooperation runs in the family for tiny fish called Trinidadian guppies, new research shows.

University of Exeter researchers studied leadership in guppies by selectively breeding for fish that differed in how likely they were to lead a scouting party to examine a predator.

They created 30 breeding pairs of the males and females most likely to lead, and another 30 of those with lowest leadership.

Three generations later they tested males and females from these lines and found that there were "pronounced differences in leadership tendency" among the two groups - with the descendants of leaders more likely to be leaders themselves.

Males bred for low leadership were found to be more aggressive and less sociable than males bred for high leadership, but no such effect was seen among females.

"We wanted to know how much leadership is an inherited characteristic, and whether it's linked to other traits," said Sylvia Dimitriadou, of the University of Exeter.

"It seems leadership among guppies is partly inherited - around a third can be explained by their pedigree, with other factors such as their social and physical environment also key.

"Among males, this appears to be linked to other social traits such as lower aggression (measured by whether fish share food or try to push rivals away) and sociability (moving as part of a shoal and switching between shoals).

"In females, leadership also passed down the generations, but without observable changes to other aspects of behaviour.

"It's not clear why this is. In guppies female and male cooperative and social behaviour differs, so it's possible that certain traits co-evolve or co-develop differently among females and males."

Traits such as boldness and tendency to explore did not diverge between the two breeding lines - meaning it was only social traits that seemed to differ alongside leadership in males.

The guppies in the study were bred in the lab, and behaviour in the face of a predator was tested by presenting them with a pike cichlid - a natural predator of Trinidadian guppies - separated by a clear pane of Perspex.

When guppies are aware of a predator, an individual or a small group leaves the relative safety of the shoal to approach and inspect, before returning to the group.

When they do this in pairs or groups, research has shown that the leading guppy is at more risk than the others.

The assessments of leadership were carried out by pairing guppies with a realistic robotic guppy, Robofish, and seeing how often the real guppy either led or hung back while approaching a predator.

In humans, research suggests leadership tendencies are moderately to largely inherited, though the genes or processes behind this remain largely unknown.

Credit: 
University of Exeter