The key to battling a pathogen hides in its genome

Many of the answers for effectively responding to a pathogen lie in its genome. Understanding the genetic code of a pathogen like Ebola or the virus that causes COVID-19 allows scientists to track its movement, predict future behavior, identify the source of the outbreak and, most importantly, develop effective vaccines and treatments. This technology was critical during the pandemic, and it will be even more so with future outbreaks.
That makes the continued development of genomic sequencing one of the most important takeaways from the pandemic, argue biologists Jason Ladner and Jason Sahl in an essay published in PLOS Biology. Genomic sequencing had a huge impact in the global response to COVID-19, and the technology improved as more researchers put it to use. To better respond to the next pandemic, we need to build on that knowledge, they write, while also recognizing the gaps in our capabilities that remain.
“The COVID-19 pandemic in many ways represented the culmination of sequencing and analysis that had been building for years,” Sahl said. “We wanted to highlight that although interest in the pandemic has waned, other threats still exist, and maintaining our momentum while also building new infrastructure will be vital for improving public health responses to existing and emerging threats.”
Why the history matters to the present and future
Ladner and Sahl, associate professors in the Department of Biological Sciences at Northern Arizona University, and their colleagues in the Pathogen & Microbiome Institute, are on the front lines of applying and analyzing cutting-edge genomic technology in the study of pathogens, and have worked with various infectious agents, including Ebola, Zika, Yersinia pestis (which causes plague), anthrax and Burkholderia pseudomallei (which causes melioidosis).
In the essay, they focus on the history of pathogens and genomic sequencing to help readers understand that the patterns we see now aren’t new. In the 1960s, scientists thought they had infectious disease resolved with the development of vaccines, antibiotics, personal hygiene and sanitation norms and more.
“What we did not fully appreciate at the time, however, was the incredible diversity of human pathogens, their capacity for rapid evolution and the dynamic nature of interactions between pathogens and their hosts,” Ladner and Sahl write. “Combined, these factors have substantially complicated our attempts to mitigate the impacts of infectious disease.”
Sixty years later, pathogens remain complicated. The biologists provide a roadmap for various stakeholders in preparation for the next pandemic: highlighting deficits in research for scientists to address; pointing out the critical need for collaboration and investment for policymakers; and explaining the history of pathogen genomic sequencing to public health officials, media, philanthropists and others so they can understand the full potential of pathogen sequencing for public health.

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Study raises possibility of immunotherapy treatment for ALS

New research reveals a type of monoclonal antibody already tested in certain forms of cancer may be a promising treatment in stopping the progression of amyotrophic lateral sclerosis, or ALS, a fatal neurodegenerative disease.
The study, led by scientists at Oregon Health & Science University, published today in the Proceedings of the National Academy of Sciences.
The study, involving a mouse model and confirmed in the tissue of human brains affected by ALS and donated after death, revealed for the first time that modulating immune cells can slow the progression of the disease. Previous research suggested a role for immune cells in ALS, but researchers this time used a high-throughput screening technique to identify a particular type of protein expressed on immune cells in the brain and spinal cord in people with ALS.
Researchers implicated the protein, known as alpha-5 integrin.
“When we blocked its expression in mice, we were able to slow down the disease,” said senior author Bahareh Ajami, Ph.D., assistant professor of molecular microbiology and immunology and behavioral neuroscience in the OHSU School of Medicine. “We hope that it will get to the clinic very soon.”
The team used a monoclonal antibody targeting a5 integrin, which had already been developed and used in treating certain forms of cancer. This means that it’s already undergone extensive safety studies to achieve approval through the Food and Drug Administration.
“Hopefully, it could be repurposed,” she said.

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Score, then rank: Researchers propose an integrated approach to grant review assessments

The public funding of science is responsible for many of the biomedical and other scientific breakthroughs on which our lives depend. However, the process through which funding decisions are made, the peer review of grant proposals, has been historically understudied, and current approaches can lead to undesirable outcomes. Writing in Research Integrity and Peer Review, Stephen A. Gallo, then affiliated with the American Institute of Biological Sciences, and Michael Pearce, Carole J. Lee, and Elena A. Erosheva from the University of Washington highlight problems related to proposal rating in grant review and propose a protocol to ameliorate them.
In many review programs, say the authors, proposals are funded primarily on the basis of reviewer ratings and summary statistics derived from them that represent reviewers’ assessment of proposal quality. Relying solely on ratings, however, can pose problems for establishing funding priorities, “especially when distinguishing between similarly rated proposals, especially for projects of high quality, where only a few minor weaknesses can make the difference between a funded project and a rejection.” Furthermore, say Gallo and colleagues, the use of ratings rubrics “often forces reviewers to penalize a project based on a series of identified but minor weaknesses, despite the fact that they may find the application overall to be potentially significant.”
To address these concerns, the authors suggest adding rankings to the traditional rating approach and describe an innovative methodology called the Mallows-Binomial, which can then produce integrated proposal scores, as well as an induced preference ordering. In so doing, the approach allows funders to consider reviewers’ scores alongside their opinions about how well the proposals stack up against one another. Pearce states that the inclusion of ranking will “more accurately distill reviewer opinion into a useful output to make an informed funding decision.”
For research funders, the authors suggest clear benefits of the Mallows-Binomial protocol in comparison with ratings-only approaches. These include “providing a ranked priority list with confidence metrics, a higher degree of discrimination between similarly rated proposals, and a robustness to outliers and reviewer inconsistencies,” features that will be important in distilling reviewer opinion “into a useful output to make the best, most informed decision” for funding crucial research.

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Sweet smell of success: Simple fragrance method produces major memory boost

When a fragrance wafted through the bedrooms of older adults for two hours every night for six months, memories skyrocketed. Participants in this study by University of California, Irvine neuroscientists reaped a 226% increase in cognitive capacity compared to the control group. The researchers say the finding transforms the long-known tie between smell and memory into an easy, non-invasive technique for strengthening memory and potentially deterring dementia.
The team’s study appears in Frontiers in Neuroscience.
The project was conducted through the UCI Center for the Neurobiology of Learning & Memory. It involved men and women aged 60 to 85 without memory impairment. All were given a diffuser and seven cartridges, each containing a single and different natural oil. People in the enriched group received full-strength cartridges. Control group participants were given the oils in tiny amounts. Participants put a different cartridge into their diffuser each evening prior to going to bed, and it activated for two hours as they slept.
People in the enriched group showed a 226% increase in cognitive performance compared to the control group, as measured by a word list test commonly used to evaluate memory. Imaging revealed better integrity in the brain pathway called the left uncinate fasciculus. This pathway, which connects the medial temporal lobe to the decision-making prefrontal cortex, becomes less robust with age. Participants also reported sleeping more soundly.
Scientists have long known that the loss of olfactory capacity, or ability to smell, can predict development of nearly 70 neurological and psychiatric diseases. These include Alzheimer’s and other dementias, Parkinson’s, schizophrenia and alcoholism. Evidence is emerging about a link between smell loss due to COVID and ensuing cognitive decrease. Researchers have previously found that exposing people with moderate dementia to up to 40 different odors twice a day over a period of time boosted their memories and language skills, eased depression and improved their olfactory capacities. The UCI team decided to try turning this knowledge into an easy and non-invasive dementia-fighting tool.
“The reality is that over the age of 60, the olfactory sense and cognition starts to fall off a cliff,” said Michael Leon, professor of neurobiology & behavior and a CNLM fellow. “But it’s not realistic to think people with cognitive impairment could open, sniff and close 80 odorant bottles daily. This would be difficult even for those without dementia.”
The study’s first author, project scientist Cynthia Woo, said: “That’s why we reduced the number of scents to just seven, exposing participants to just one each time, rather than the multiple aromas used simultaneously in previous research projects. By making it possible for people to experience the odors while sleeping, we eliminated the need to set aside time for this during waking hours every day.”
The researchers say the results from their study bear out what scientists learned about the connection between smell and memory.

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Scientists develop breath test that rapidly detects COVID-19 virus

Scientists at Washington University in St. Louis have developed a breath test that quickly identifies those who are infected with the virus that causes COVID-19. The device requires only one or two breaths and provides results in less than a minute.
The study is available online in the journal ACS Sensors. The same group of researchers recently published a paper in the journal Nature Communications about an air monitor they had built to detect airborne SARS-CoV-2 — the virus that causes COVID-19 — within about five minutes in hospitals, schools and other public places.
The new study is about a breath test that could become a tool for use in doctors’ offices to quickly diagnose people infected with the virus. If and when new strains of COVID-19 or other airborne pathogenic diseases arise, such devices also could be used to screen people at public events. The researchers said the breath test also has potential to help prevent outbreaks in situations where many people live or interact in close quarters — for example aboard ships, in nursing homes, in residence halls at colleges and universities or on military bases.
“With this test, there are no nasal swabs and no waiting 15 minutes for results, as with home tests,” said co-corresponding author Rajan K. Chakrabarty, PhD, the Harold D. Jolley Career Development Associate Professor of Energy, Environment & Chemical Engineering at the McKelvey School of Engineering. “A person simply blows into a tube in the device, and an electrochemical biosensor detects whether the virus is there. Results are available in about a minute.”
The biosensor used in the device was adapted from an Alzheimer’s disease-related technology developed by scientists at Washington University School of Medicine in St. Louis to detect amyloid beta and other Alzheimer’s disease-related proteins in the brains of mice. The School of Medicine’s John R. Cirrito, PhD, a professor of neurology, and Carla M. Yuede, PhD, an associate professor of psychiatry — both also co-corresponding authors on the study — used a nanobody, an antibody from llamas, to detect the virus that causes COVID-19.
Chakrabarty and Cirrito said the breath test could be modified to simultaneously detect other viruses, including influenza and respiratory syncytial virus (RSV). They also believe they can develop a biodetector for any newly emerging pathogen within two weeks of receiving samples of it.
“It’s a bit like a breathalyzer test that an impaired driver might be given,” Cirrito said. “And, for example, if people are in line to enter a hospital, a sports arena or the White House Situation Room, 15-minute nasal swab tests aren’t practical, and PCR tests take even longer. Plus, home tests are about 60% to 70% accurate, and they produce a lot of false negatives. This device will have diagnostic accuracy.”
The researchers began working on the breath test device — made with 3D printers — after receiving a grant from the National Institutes of Health (NIH) in August 2020, during the first year of the pandemic. Since receiving the grant, they’ve tested prototypes in the laboratory and in the Washington University Infectious Diseases Clinical Research Unit. The team continues to test the device, to further improve its efficacy at detecting the virus in people.

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Study sheds new light on how animals navigate their environment

Scientists have demonstrated how mice choose between three different strategies to navigate through their surroundings towards a goal.
Their study, published today as an eLife Reviewed Preprint, provides what the editors describe as a valuable new behavioural apparatus for differentiating the strategies animals use to orient themselves in an environment.
Animals can use a number of different strategies, or a combination of them, to move through their surroundings. How they select these strategies based on the nature and familiarity of their environment is unclear.
One way of studying this is by using the Barnes maze, in which rodents explore a circular arena until they find an escape box located under one of several holes along the outskirts of the arena. Simple criteria, such as the number of visited holes, are used to classify the strategy employed by mice in each trial of the maze.
“Typical Barnes mazes work under the assumption that the same strategy is maintained across a whole trial, so it is unclear whether they accurately capture the full range of navigational strategies used by mice,” explains co-lead author Ju-Young Lee, a PhD student at the Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
To address this shortcoming, Lee and colleagues developed an automated variant of the Barnes Maze, which allowed them to randomise the start and goal positions for each individual trial, without interfering with the experiment.
“Our maze is similar to the Barnes maze in that mice explore an open arena and navigate to a goal chosen among 24 doors evenly spaced along the edge of the arena,” says co-lead author, Dahee Jung, Postdoc at the Brain Science Institute, KIST. “The difference with ours is that it features two luminous objects inside the arena as orienting cues, and the mice start at the edge, instead of the centre.”
The team monitored the trajectories of 10 male and 10 female mice completing the maze over 15 days. During this time — the acquisition phase — the mice performed 10 trials per day. Next, the team performed a probe test, in which the goal door remained closed and mice were allowed to explore the arena for two minutes. Finally, for a further four days — the reversal phase — the mice performed the same task as in the acquisition phase, but with a different goal location.

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Closure of Pittsburgh coal-processing plant tied to local health gains

The closure in January 2016 of one of Pittsburgh’s biggest coal-processing plants led to immediate and lasting declines in emissions of fossil fuel-related air pollutants. These in turn were linked to near-instant decreases in local heart-related emergency department visits and hospitalizations for cardiovascular diseases, a new study shows. The impact of the closure persisted through at least December 2018, the last month for which data were analyzed.
Led by researchers at NYU Grossman School of Medicine, the study was designed to assess the short- and longer-term health effects of the shutdown of the Shenango Coke Works facility, which for more than 50 years produced coke, a coal-derived product needed for steelmaking. Before closing under community pressure, the plant had incurred millions of dollars in government fines for air and water pollution.
Although the study, performed in a real-life situation, did not demonstrate a cause-and-effect link between any individual’s health and the plant closure, the results of the “natural experiment” showed a strong overall statistical association between the closure and measures of improved health, such as reduced visits to the emergency department, the researchers say.
Publishing in the journal Environmental Health Research online July 31, the study showed that average daily levels of sulfur dioxide, a major toxic chemical component in air pollution and by-product of coke-making, fell by 90% at government air-monitoring stations near the plant and by 50% at another air-monitoring station roughly 10 kilometers (more than six miles) away. Arsenic in particulate matter, another coal-combustion by-product that can be inhaled, fell by 66%.
Analyses of state health records showed that average weekly visits to the local emergency departments for heart-related problems decreased by 42% immediately after the shutdown.
Similar downward trends were observed locally over the long term, with 33 fewer average yearly hospitalizations for heart disease from 2016 through 2018 compared to the three years preceding the plant closure. This included 13 fewer average yearly hospitalizations for ischemic heart disease (typically heart attack) and 12 fewer average yearly hospitalizations for cerebrovascular events (most often stroke).
By contrast, study findings showed no corresponding postclosure drop in trauma-related injuries as reported in visits to the emergency department, an indicator that the cardiovascular health gains were not due to some overall drop in population or in accidents needing emergency care.

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While resolving a key asthma challenge, researchers also create a new method to detect proteins in body fluids and other materials

Based on decades of work to uncover the underlying mechanisms of asthma and other respiratory conditions, researchers at McMaster University and St. Joseph’s Healthcare Hamilton have produced a simple, rapid test that can identify the presence of a key driver of severe asthma.
John Brennan, director of McMaster’s Biointerfaces Institute, and Parameswaran Nair, a respirologist at the St. Joseph’s-based Firestone Institute for Respiratory Health, led the creation of a new rapid test that can quickly and accurately identify white blood cells known as eosinophils, even when they are present in complex biological samples such as sputum, by tracking their protein signatures.
Having access to quick and reliable information about the presence of eosinophils can guide physicians in making important decisions about patient care.
The test looks similar to the familiar COVID-19 home test, which makes it readily adaptable to mass manufacturing once it is approved for clinical use.
To create the new test, the researchers developed and deployed a protein-targeting element known as a DNAzyme and modified it for use in the rapid test.
First isolated in 1994, DNAzymes have primarily been generated for detection of metals or bacterial targets. Until now, no one had succeeded in using DNAzymes to target specific protein markers in any context.
Now that the team has overcome this obstacle, Brennan believes the new test platform could be adapted to identify any material of biological origin by detecting its protein signature.

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Canada launches warning labels on each cigarette

Published16 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Health CanadaBy Chloe KimBBC NewsCanada will be the first nation to start printing warnings directly onto individual cigarettes in a bid to deter young people from starting smoking and encourage others to quit. The warnings, which will be in English and French, will include phrases like “Cigarettes cause cancer” and “Poison in every puff”.The new regulations go into effect on Tuesday.Starting next year, Canadians will begin to see the new warning labels.By July 2024 manufacturers will have to ensure the warnings are on all king-size cigarettes sold, and by April 2025 all regular-size cigarettes and little cigars with tipping paper and tubes must include the warnings. The phrases will appear by the filter, including warnings about harming children, damaging organs and causing impotence and leukaemia.In May, Health Canada said the new regulations “will make it virtually impossible to avoid health warnings” on tobacco products.A second set of six phrases is expected to be printed on cigarettes in 2026.The move is part of Canada’s effort to reduce tobacco use to less than 5% by 2035 and follows a 75-day public consultation period that was launched last year.Canada has required the printing of warning labels on cigarette packages since 1989 and in 2000 the country adopted pictorial warning requirements for tobacco product packages.Health Canada said it plans to expand on warnings by printing additional warning labels inside the packages themselves, and introducing a new external warning messages.Dr Robert Schwartz, of the University of Toronto, told BBC News it was good news that Canada was “moving forward with this innovation”. “Health warnings on individual cigarettes will likely push some people who smoke to make a quit attempt and may prevent some young people from starting to smoke,” he said.He also pointed to New Zealand, which has introduced very low nicotine cigarettes, as a leader in limiting the use of tobacco. Mr Schwartz added: “These are the kinds of measures needed if we are serious about decreasing tobacco use.”Tobacco use continues to kill 48,000 Canadians each year.”Tobacco use continues to be one of Canada’s most significant public health problems, and is the country’s leading preventable cause of disease and premature death in Canada,” Public Services Minister Jean-Yves Duclos has previously said.The Canadian Cancer Society, Canada’s Heart and Stroke Foundation and the Canadian Lung Association have all praised the warning labels, saying they hope the measures will deter people, especially young people, from taking up smoking in the first place.Cigarette smoking is widely regarded as a risk factor for lung cancer, heart disease and stroke.In Canada, the rate of smokers aged 15 years or older is around 10%, according to a national 2021 Tobacco and Nicotine survey but electronic cigarette use has been on the rise. More on this storyEvery Canadian cigarette to carry health warningPublished31 MayWho are the smokers that haven’t quit?Published24 July 2019Why US lags behind on graphic cigarette warningsPublished16 August 2019

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Henrietta Lacks’s Family Settles with Company That Used Her Cells

Ms. Lacks’s family had accused Thermo Fisher Scientific of profiting from her cells, which have contributed to revolutionary advances in medicine, without seeking their permission.The family of Henrietta Lacks, the Black woman whose cancer cells were taken without consent and used to pioneer numerous medical discoveries, reached a settlement on Monday with a biotechnology company that had used the cells.In a lawsuit filed in October 2021, descendants of Ms. Lacks, who died in 1951, accused the company, Thermo Fisher Scientific, of selling the cells and trying to secure intellectual property rights on the products the cells were used to help develop without compensating the family or seeking their permission or approval.The terms of the settlement are confidential, lawyers for both parties said in a statement.Thermo Fisher, a Massachusetts-based biotechnology company, and the legal team for Ms. Lacks’s family released identical statements announcing the settlement.“The parties are pleased that they were able to find a way to resolve this matter outside of Court and will have no further comment,” the statements said.Ms. Lacks was being treated for cervical cancer at Johns Hopkins Hospital in Baltimore in 1951 when a sample of her cells were taken without her knowledge. The cell line named for her, HeLa, became the cornerstone of many medical and scientific innovations, including vaccines for polio and the coronavirus. But Ms. Lacks died that same year, and her family did not know about her contribution to medical science for more than two decades.On Tuesday, which would have been Ms. Lacks’s 103rd birthday, members of her family gathered at a news conference to celebrate the settlement.A grandson, Alfred Lacks Carter Jr., said, “it could not have been a more fitting day for her to have justice and for her family to have relief.”“It was a long fight, over 70 years, and Henrietta Lacks gets her day,” he said.One of the family’s lawyers, Chris Ayers, suggested that similar lawsuits would follow.“The fight against those who profit, and chose to profit, off the deeply unethical and unlawful history and origins of the HeLa cells will continue,” he said.Ms. Lacks, a mother of five, died in October 1951. She was 31.Eight months earlier, she had learned she had cervical cancer after being admitted to a racially segregated ward at Johns Hopkins Hospital in Baltimore. Doctors removed a sample of cells from the tumor in her cervix without her knowledge or consent and gave them to a medical researcher at Johns Hopkins University. The researcher found that her cells were the first to reproduce in a laboratory, outside the body.Most cells die within days, but because Ms. Lacks’s cells continued to multiply, researchers and scientists could use them to do things such as test how the polio virus infects cells and causes disease.Research using the HeLa cells has led to the development of vaccines for polio and the coronavirus, and to treatments for diseases including cancer, Parkinson’s and the flu.The cells have been used by researchers around the world and have been cited in more than 110,000 scientific publications, according to the National Institutes of Health.Ms. Lacks’s family was not told about the world-changing discovery and did not find out about the cell line until 1973, according to “The Immortal Life of Henrietta Lacks,” a book by Rebecca Skloot that was turned into a movie featuring Oprah Winfrey as Ms. Lacks’s daughter Deborah.Ms. Lacks’s descendants have said they are proud of her contribution, but angry about how she was treated by the medical establishment. These frustrations have been made worse with the commercialization of her cells, they said.The family’s lawsuit against Thermo Fisher said the company had “made staggering profits by using the HeLa cell line — all while Ms. Lacks’ Estate and family haven’t seen a dime.”“Thermo Fisher Scientific’s choice to continue selling HeLa cells in spite of the cell lines’ origin and the concrete harms it inflicts on the Lacks family can only be understood as a choice to embrace a legacy of racial injustice embedded in the U.S. research and medical systems,” the lawsuit said.Thermo Fisher tried to dismiss the case, arguing that the lawsuit was filed after the statute of had limitations expired, The Baltimore Sun reported. Lawyers for the family said the limit should not apply because the company continued to benefit financially from the cells.

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