AND HUMANS INFECTED MINKS

SARS-CoV-2 jumped from bats to humans without much change

PLOS

Research News

 

IMAGE: SCHEMATIC OF OUR PROPOSED EVOLUTIONARY HISTORY OF THE NCOV CLADE AND PUTATIVE EVENTS LEADING TO THE EMERGENCE OF SARS-COV-2. view more 

CREDIT: MACLEAN OA, ET AL. (2021), NATURAL SELECTION IN THE EVOLUTION OF SARS-COV-2 IN BATS CREATED A GENERALIST VIRUS AND HIGHLY CAPABLE HUMAN PATHOGEN. PLOS BIOL 19(3): E3001115. CC-BY...

How much did SARS-CoV-2 need to change in order to adapt to its new human host? In a research article published in the open access journal PLOS Biology Oscar MacLean, Spyros Lytras at the University of Glasgow, and colleagues, show that since December 2019 and for the first 11 months of the SARS-CoV-2 pandemic there has been very little 'important' genetic change observed in the hundreds of thousands of sequenced virus genomes.

The study is a collaboration between researchers in the UK, US and Belgium. The lead authors Prof David L Robertson (at the MRC-University of Glasgow Centre for Virus Research, Scotland) and Prof Sergei Pond (at the Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia) were able to turn their experience of analysing data from HIV and other viruses to SARS-CoV-2. Pond's state-of-the-art analytical framework, HyPhy, was instrumental in teasing out the signatures of evolution embedded in the virus genomes and rests on decades of theoretical knowledge on molecular evolutionary processes.

First author Dr Oscar MacLean explains, "This does not mean no changes have occurred, mutations of no evolutionary significance accumulate and 'surf' along the millions of transmission events, like they do in all viruses." Some changes can have an effect; for example, the Spike replacement D614G which has been found to enhance transmissibility and certain other tweaks of virus biology scattered over its genome. On the whole, though, 'neutral' evolutionary processes have dominated. MacLean adds, "This stasis can be attributed to the highly susceptible nature of the human population to this new pathogen, with limited pressure from population immunity, and lack of containment, leading to exponential growth making almost every virus a winner."

Pond comments, "what's been so surprising is just how transmissible SARS-CoV-2 has been from the outset. Usually viruses that jump to a new host species take some time to acquire adaptations to be as capable as SARS-CoV-2 at spreading, and most never make it past that stage, resulting in dead-end spillovers or localised outbreaks."

Studying the mutational processes of SARS-CoV-2 and related sarbecoviruses (the group of viruses SARS-CoV-2 belongs to from bats and pangolins), the authors find evidence of fairly significant change, but all before the emergence of SARS-CoV-2 in humans. This means that the 'generalist' nature of many coronaviruses and their apparent facility to jump between hosts, imbued SARS-CoV-2 with ready-made ability to infect humans and other mammals, but those properties most have probably evolved in bats prior to spillover to humans.

Joint first author and PhD student Spyros Lytras adds, "Interestingly, one of the closer bat viruses, RmYN02, has an intriguing genome structure made up of both SARS-CoV-2-like and bat-virus-like segments. Its genetic material carries both distinct composition signatures (associated with the action of host anti-viral immunity), supporting this change of evolutionary pace occurred in bats without the need for an intermediate animal species."

Robertson comments, "the reason for the 'shifting of gears' of SARS-CoV-2 in terms of its increased rate of evolution at the end of 2020, associated with more heavily mutated lineages, is because the immunological profile of the human population has changed." The virus towards the end of 2020 was increasingly coming into contact with existing host immunity as numbers of previously infected people are now high. This will select for variants that can dodge some of the host response. Coupled with the evasion of immunity in longer-term infections in chronic cases (e.g., in immunocompromised patients), these new selective pressures are increasing the number of important virus mutants.

It's important to appreciate SARS-CoV-2 still remains an acute virus, cleared by the immune response in the vast majority of infections. However, it's now moving away faster from the January 2020 variant used in all of the current vaccines to raise protective immunity. The current vaccines will continue to work against most of the circulating variants but the more time that passes, and the bigger the differential between vaccinated and not-vaccinated numbers of people, the more opportunity there will be for vaccine escape. Robertson adds, "The first race was to develop a vaccine. The race now is to get the global population vaccinated as quickly as possible."

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Research Article

Peer reviewed; Experimental study; Animals

In your coverage please use these URLs to provide access to the freely available articles in PLOS Biology: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001115

Citation: MacLean OA, Lytras S, Weaver S, Singer JB, Boni MF, Lemey P, et al. (2021) Natural selection in the evolution of SARS-CoV-2 in bats created a generalist virus and highly capable human pathogen. PLoS Biol 19(3): e3001115. https://doi.org/10.1371/journal.pbio.3001115

Funding: DLR is funded by the Medical Research Council (MC_UU_1201412) and Wellcome Trust (220977/Z/20/Z). OAM is funded by the Wellcome Trust (206369/Z/17/Z). SLKP and SW are supported in part by the National Institutes of Health (R01 AI134384 (NIH/NIAID)) and the National Science Foundation (award 2027196). PL acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS), the European Union's Horizon 2020 project MOOD (874850), the Wellcome Trust through project 206298/Z/17/Z (The Artic Network) and the Research Foundation -- Flanders (`Fonds voor Wetenschappelijk Onderzoek -- Vlaanderen', G066215N, G0D5117N and G0B9317N). MFB is funded by a grant from the Bill and Melinda Gates Foundation (INV-005517) and by NIH/NIAID Center of Excellence in Influenza Research and Surveillance contract (HHS N272201400007C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing in

An unusual creature is coming out of winter's slumber. Here's why scientists are excited.

Duke Lemur Center recreates the seasonal swings of native habitat, helping to unlock the secrets of hibernation.

DUKE UNIVERSITY

Research News

 

IMAGE: RESEARCHERS AT THE DUKE LEMUR CENTER HAVE BEEN CHANGING UP THEIR CARE TO MORE CLOSELY MATCH THE SEASONAL FLUCTUATIONS THEY EXPERIENCE IN THE WILD. view more 

CREDIT: PHOTO BY DAVID HARING, DUKE LEMUR CENTER

DURHAM, N.C. -- If you binged on high-calorie snacks and then spent the winter crashed on the couch in a months-long food coma, you'd likely wake up worse for wear. Unless you happen to be a fat-tailed dwarf lemur.

This squirrel-sized primate lives in the forests of Madagascar, where it spends up to seven months each year mostly motionless and chilling, using the minimum energy necessary to withstand the winter. While zonked, it lives off of fat stored in its tail.

Animals that hibernate in the wild rarely do so in zoos and sanctuaries, with their climate controls and year-round access to food. But now our closest hibernating relative has gone into true, deep hibernation in captivity for the first time at the Duke Lemur Center.

"They did not disappoint," said research scientist Marina Blanco, who led the project. "Indeed, our dwarf lemurs hibernated just like their wild kin do in western Madagascar."

The researchers say recreating some of the seasonal fluctuations of the lemurs' native habitat might be good for the well-being of a species hardwired for hibernation, and also may yield insights into metabolic disorders in humans.

"Hibernation is literally in their DNA," Blanco said.

Blanco has studied dwarf lemurs for 15 years in Madagascar, fitting them with tracking collars to locate them when they are hibernating in their tree holes or underground burrows. But what she and others observed in the wild didn't square with how the animals behaved when cared for in captivity.

Captive dwarf lemurs are fed extra during the summer so they can bulk up like they do in the wild, and then they'll hunker down and let their heart rate and temperature drop for short bouts -- a physiological condition known as torpor. But they rarely stay in this suspended state for longer than 24 hours. Which got Blanco to wondering: After years in captivity, do dwarf lemurs still have what it takes to survive seasonal swings like their wild counterparts do? And what can these animals teach us about how to safely put the human body on pause too, slowing the body's processes long enough for, say, life-saving surgery or even space travel?

To find out, Duke Lemur Center staff teamed up to build fake tree hollows out of wooden boxes and placed them in the dwarf lemurs' indoor enclosures, as a haven for them to wait out the winter. To mimic the seasonal changes the lemurs experience over the course of the year in Madagascar, the team also gradually adjusted the lights from 12 hours a day to a more "winter-like" 9.5 hours, and lowered the thermostat from 77 degrees Fahrenheit to the low 50s.

The animals were offered food if they were awake and active, and weighed every two weeks, but otherwise they were left to lie.

It worked. In the March 11 issue of the journal Scientific Reports, the researchers show for the first time that fat-tailed dwarf lemurs can hibernate quite well in captivity.

For four months, the eight lemurs in the study spent some 70% of their time in metabolic slow-motion: curled up, cool to the touch, barely moving or breathing for up to 11 days at a stretch, showing little interest in food -- akin to their wild counterparts.

Now that spring is afoot in North Carolina and the temperatures are warming, the lemurs are waking up. Their first physical exams after they emerged showed them to be 22% to 35% lighter than they were at the start but otherwise healthy. Their heart rates are back up from just eight beats per minute to about 200, and their appetites have returned.

"We've been able to replicate their wild conditions well enough to get them to replicate their natural patterns," said Erin Ehmke, who directs research at the center.

Females were the hibernation champs, out-stuporing the males and maintaining more of their winter weight. They need what's left of their fat stores for the months of pregnancy and lactation that typically follow after they wake up, Blanco said.

Study co-author Lydia Greene says the next step is to use non-invasive research techniques such as metabolite analysis and sensors in their enclosures to better understand what dwarf lemurs do to prepare their bodies and eventually bounce back from months of standby mode -- work that could lead to new treatments for heart attacks, strokes, and other life-threatening conditions in humans.

Blanco suspects the impressive energy-saving capabilities of these lemurs may also relate to another trait they possess: longevity. The oldest dwarf lemur on record, Jonas, died at the Duke Lemur Center at the age of 29. The fact that dwarf lemurs live longer than non-hibernating species their size suggests that something intrinsic to their biological machinery may protect against aging.

"But until now, if you wanted to study hibernation in these primates, you needed to go to Madagascar to find them in the act," Blanco said. "Now we can study hibernation here and do more close monitoring."

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This research was supported by the Duke Lemur Center.

CITATION: "On the Modulation and Maintenance of Hibernation in Captive Dwarf Lemurs," Marina B. Blanco, Lydia K. Greene, Robert Schopler, Cathy V. Williams, Danielle Lynch, Jenna Browning, Kay Welser, Melanie Simmons, Peter H. Klopfer, Erin E. Ehmke. Scientific Reports, March 11, 2021. DOI: 10.1038/s41598-021-84727-3.

AND ONCE THE FAT TAILED DWARF LEMUR WAKES UP THEY ARE WOKE!

Farm-level study shows rising temperatures hurt rice yields

NORTH CAROLINA STATE UNIVERSITY

Research News

 

A study of the relationship between temperature and yields of various rice varieties, based on 50 years of weather and rice-yield data from farms in the Philippines, suggests that warming temperatures negatively affect rice yields.

Recent varieties of rice, bred for environmental stresses like heat, showed better yields than both traditional rice varieties and modern varieties of rice that were not specifically bred to withstand warmer temperatures. But the study found that warming adversely affected crop yields even for those varieties best suited to the heat. Overall, the advantage of varieties bred to withstand increased heat was too small to be statistically significant.

One of the top 10 countries globally in rice production, the Philippines is also a top-10 rice importer, as domestic supply cannot meet demand.

Roderick Rejesus, a professor and extension specialist of agricultural and resource economics at North Carolina State University and the corresponding author of a paper that describes the study, says that teasing out the effects of temperature on rice yields is important to understand whether rice-breeding efforts have helped address the environmental challenges faced by modern society, such as global warming.

The study examined rice yields and atmospheric conditions from 1966 to 2016 in Central Luzon, the major rice-growing region of the Philippines. Rejesus and study colleagues were able to utilize farm-level data of rice yields and area weather conditions in four-to-five-year increments over the 50-year period, a rare data trove that allowed the researchers to painstakingly examine the relationship between rice yield and temperature in actual farm environments.

"This rich data set allowed us to see what was actually happening at the farm level, rather than only observing behavior at higher levels of aggregation like in provinces or districts," Rejesus said.

The study examined three general rice varieties planted during those 50 years: traditional rice varieties; "early modern varieties" planted after the onset of the Green Revolution, which were bred for higher yields; and "recent modern varieties" bred for particular characteristics, like heat or pest resistance, for example.

Perhaps as expected, the study showed that, in the presence of warming, recent modern varieties had the best yields when compared with the early modern and traditional varieties, and that early modern varieties outperformed traditional varieties. Interestingly, some of the early modern varieties may have also mitigated heat challenges given their smaller "semi-dwarf" plant architecture, even though they were not bred to specifically resist heat.

"Taken all together, there are two main implications here," Rejesus said. "The first is that, at the farm level, there appears to be a 'yield gap' between how rice performs in breeding trials and on farms, with farm performance of recent varieties bred to be more tolerant to environmental stresses not being statistically different relative to the older varieties.

"The second is that rice breeding efforts may not have reached their full potential such that it may be possible to produce new varieties that will statistically perform better than older varieties in a farm setting."

Rejesus also acknowledged that the study's modest sample size may have contributed to the inability to find statistical significance in the differences in warming impacts between rice varietal yields.

"This paper has implications for other rice-breeding countries, like Vietnam, because the timing of the release of various rice varieties is somewhat similar to that of the Philippines," Rejesus said. "Plant-breeding institutions can learn from this type of analysis, too. It provides guidance as to where research funding may be allocated by policymakers to further improve the high temperature tolerance of rice varieties available to farmers."

Rejesus plans to further study other agricultural practices and innovations that affect crop yields, including an examination of cover crops, or plants grown on cropland in the off season that aim to keep soils healthy, to gauge whether they can mitigate the adverse impacts of a changing climate.

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The paper appears in the American Journal of Agricultural Economics. Former NC State Ph.D. student Ruixue Wang is the paper's first author. Jesse B. Tack from Kansas State University, Joseph V. Balagtas of Purdue University and Andy D. Nelson of the University of Twente are other paper co-authors. Support for the work was provided in part by the U.S. Department of Agriculture's NIFA Hatch Project No. NC02696.

- kulikowski -

Note to editors: An abstract of the paper follows.

Quantifying the Yield Sensitivity of Modern Rice Varieties to Warming Temperatures: Evidence from the Philippines

Authors: Ruixue Wang and Roderick Rejesus, North Carolina State University; Jesse B. Tack, Kansas State University; Joseph V. Balagtas, Purdue University; and Andy D. Nelson, University of Twente

Published: March 4, 2021 in American Journal of Agricultural Economics

DOI: 10.1111/ajae.12210

Abstract: This study examines the relationship between yields of modern rice varieties and warming temperatures. Data from a long-running farm-level survey in the Philippines, with rich information on planted rice varieties, allow us to estimate fixed effect econometric models of rice yields. We find that increases in temperature, especially minimum temperatures, have statistically significant negative impacts on rice yields. Point estimates of the marginal effect of higher temperatures on rice yields indicate that early modern varieties bred primarily for higher yields, pest resistance, and/or grain quality traits (i.e., not necessarily abiotic stress tolerance) tend to be more resilient to heat events than traditional rice varieties. Moreover, the marginal effect point estimates also suggest that more recent rice varieties bred for better tolerance to abiotic stresses are likely more resilient to warming than both traditional varieties and early modern varieties. Notwithstanding the heat resilience pattern suggested by these point estimates, we are unable to find statistically significant differences in the marginal yield response to warming across these three rice varietal groups. These results provide suggestive evidence that rice breeding efforts have improved resilience to warming temperatures and point to several interesting future research directions.

WAGES FOR HOUSEWORK

School closures 'sideline' working mothers

In states where elementary schools primarily offered remote instruction, the gender gap between parents in workforce surpassed 23 percentage points in 2020

"Now, more than ever, it is crucial that federal and state governments invest in expanding the public care infrastructure for children of all ages."

WASHINGTON UNIVERSITY IN ST. LOUIS

Research News

 

Decades of feminist gains in the workforce have been undermined by the COVID-19 pandemic, which has upended public education across the United States, a critical infrastructure of care that parents -- especially mothers -- depend on to work, according to new research from Washington University in St. Louis.

The research, published in Gender & Society, draws on new data from the Elementary School Operating Status (ESOS) database to show that the gender gap between mothers and fathers in the labor force has grown significantly since the onset of the pandemic in states where schools primarily offered remote instruction.

And if these circumstances continue, it could deliver a long-lasting blow to mothers' lifetime earnings and occupational trajectories.

At the start of the 2019-20 school year, U.S. mothers' rate of labor participation was, on average, 18 percentage points less than fathers'. By last September, the gap grew to over 23 percentage points in states where schools primarily offered remote instruction. In comparison, in states where in-person instruction was most common, the gender gap in parents' labor force participation grew by less than 1 percentage point, to 18.4%.

"Our research shows schools are a vital source of care for young children, and without full-time, in-person instruction, mothers have been sidelined from the labor force," said Caitlyn Collins, assistant professor of sociology in Arts & Sciences and co-author of the study.

"The longer these conditions remain in place, the more difficult it may be for mothers to fully recover from prolonged spells of non-employment, resulting in reduced occupational opportunities and lifetime earnings."

As the pandemic continues into the spring, states with significantly curtailed in-person learning will likely continue to see low maternal labor force participation with the potential for devastating, long-term employment effects for many women with children, Collins added.

How do school reopening plans impact working parents?

While the primary function of schools is children's education, they also provide an expansive infrastructure of care -- especially for elementary school-age children -- that parents, businesses and the economy rely upon, Collins said. COVID-19 has strained that infrastructure in unprecedented ways.

States have varied considerably in their approaches to slow the virus' spread and reopen schools, resulting in a patchwork structure of K-12 education across the United States.

Collins and co-authors -- Liana Christin Landivar at the Maryland Population Research Center; Leah Ruppanner at the University of Melbourne; and William Scarborough at the University of North Texas -- wanted to understand the nature and magnitude of school closures across states.

They used the ESOS database to measure the percentage of school districts offering in-person, remote and hybrid instruction models for elementary schools by state in September 2020. Then, they linked the data to the Current Population Survey to evaluate the association between school reopenings and parents' labor force participation rates, comparing such 2020 rates with those observed pre-pandemic in 2019.

In the paper, the authors describe results from the 26 states currently available in ESOS, and highlight three states as illustrative examples of the consequences of various reopening statuses.

Their findings illustrate the critical role schools play not only in supporting children's well-being, but also enabling parents, especially mothers, to maintain employment. Absent fathers' equal participation at home, mothers bear the brunt of responsibility for childrearing, both before and during the pandemic, according to Collins.

Maryland - where schools across the state primarily opened remotely in 2020 - experienced the largest drop in mothers' labor force participation. In 2019, Maryland mothers with elementary-age children had a 90% predicted probability of being in the labor force. When schools opened in 2020, that probability dropped to 74%, representing a 16-point drop. In comparison, Maryland fathers' predicted probability of labor force participation dropped by 5 percentage points, from 92% to 87% - a statistically insignificant change, the authors wrote.

Just 200 miles away, New York took a different approach: Nearly half of the elementary schools in the state offered hybrid programs consisting of a mix of remote and in-person education. Researchers found that mothers' labor force participation in New York declined by 7 percentage points, from 79% to 72%. Fathers' labor force participation dropped by 4 percentage points, from 96% to 92%. Neither of these drops was statistically significant.

Finally, in Texas - where more than half of school districts offered full-time, in-person education for elementary students - mothers' labor force participation dropped by 10 percentage points, from 77% to 67%, and fathers' from 96% to 93%. While this was a larger shift than observed in New York, it was still substantially smaller than the changes observed in Maryland.

Across all states, mothers' work attachment fell to a greater extent than fathers', but the gap is widest in states, like Maryland, where schooling was fully remote at the start of the school year.

Upon completion in spring 2021, the ESOS database will be made publicly available via the Open Science Framework, offering the reopening status of all elementary school districts in the country serving more than 500 students, or approximately 9,000 school districts.

'Something had to give'

One in three U.S. women who left employment since the onset of the COVID-19 pandemic cite childcare demands as a primary reason for their departure. Perhaps that's not surprising, though. Preliminary evidence suggests that gender inequality in the domestic division of labor worsened under the pandemic, Collins said.

Collins, Landivar, Ruppanner and Scarborough have been studying the impact of the pandemic on mothers' paid work since the first shutdowns in March 2020. Their early analysis found that mothers were more likely to reduce their work hours or exit the labor force altogether - even when both parents were able to telecommute. They suggest this is likely because mothers picked up a larger share of housework, childcare and homeschooling than fathers.

"Mothers have also reported greater increases in anxiety, depression and disturbed sleep compared to fathers, especially after experiencing a job loss or an increased housework or childcare load," said Ruppanner, associate professor of sociology at the University of Melbourne.

"Without more support from fathers, employers and the government, something had to give under this unsustainable pressure. What seems to be giving is mothers' employment," Collins said.

The fallout will last well beyond the pandemic When mothers are forced to choose between their families and jobs, it impacts not only their immediate financial stability, but also their psychological well-being, economic independence and lifetime occupational attainment and earnings.

As the current research illustrates, mothers have paid the price of the childcare crisis created by the COVID-19 pandemic.

"This is an injustice with long-term consequences for mothers' job prospects and economic stability," the researchers wrote.

"These are not personal problems, but deeply political issues that require policy interventions. Well-funded and evidence-based reopening plans are necessary to allow children to return to school face-to-face, and to allow parents to engage in paid work.

"Now, more than ever, it is crucial that federal and state governments invest in expanding the public care infrastructure for children of all ages."

 

Children's preventive healthcare costs dropped under ACA: BU study

BOSTON UNIVERSITY SCHOOL OF MEDICINE

Research News

 

The Affordable Care Act (ACA) dramatically increased children's preventive healthcare while reducing out-of-pocket costs, according to a new Boston University School of Public Health (BUSPH) study.

Published in JAMA Network Open, the study found that checkups with out-of-pocket costs dropped from 54.2% of visits in 2010 (the year the ACA passed) to 14.5% in 2018.

"This is a great feather in the cap of the ACA, even though there is still some work to do," says study lead author Dr. Paul Shafer, assistant professor of health law, policy & management at BUSPH.

"We found that one in seven families were still charged something for their children's well visits," he says, "and costs can be a barrier to parents keeping their kids up-to-date with preventive care."

Shafer and colleagues analyzed national health insurance claims data from 2006 through 2018 for children 0 to 17 years old.

Even before the ACA became law in 2010, the researchers saw improving trends in preventive pediatric care. The proportion of children who went to the doctor at least once per year without having a preventive checkup dropped from 39.3% in 2006 to 29.0% in 2018. The researchers also found a 60% increase in the proportion of so-called "sick" visits (for anything other than a checkup) that included one or more preventive services, such as immunizations or recommended screenings. The researchers write that this may mean pediatricians are increasingly taking advantage of any opportunity they can to provide preventive care.

"As deductibles and copays continue to rise, the promise of free preventive care has become a very popular benefit of the ACA," Shafer says. "According to our results, we are continuing to get better at delivering on that promise for children."

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About Boston University School of Public Health

Founded in 1976, Boston University School of Public Health is one of the top five ranked private schools of public health in the world. It offers master's- and doctoral-level education in public health. The faculty in six departments conduct policy-changing public health research around the world, with the mission of improving the health of populations--especially the disadvantaged, underserved, and vulnerable--locally and globally.

Study finds cancer cells may evade chemotherapy by going dormant

WEILL CORNELL MEDICINE

Research News

 

Cancer cells can dodge chemotherapy by entering a state that bears similarity to certain kinds of senescence, a type of "active hibernation" that enables them to weather the stress induced by aggressive treatments aimed at destroying them, according to a new study by scientists at Weill Cornell Medicine. These findings have implications for developing new drug combinations that could block senescence and make chemotherapy more effective.

In a study published Jan. 26 in Cancer Discovery, a journal of the American Association for Cancer Research, the investigators reported that this biologic process could help explain why cancers so often recur after treatment. The research was done in both organoids and mouse models made from patients' samples of acute myeloid leukemia (AML) tumors. The findings were also verified by looking at samples from AML patients that were collected throughout the course of treatment and relapse.

"Acute myeloid leukemia can be put into remission with chemotherapy, but it almost always comes back, and when it does it's incurable," said senior author Dr. Ari M. Melnick, the Gebroe Family Professor of Hematology and Medical Oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. "A longstanding question in the field has been, 'Why can't you get rid of all the cancer cells?' A similar question can be posed for many other types of aggressive cancer in addition to AML."

For years, cancer researchers have studied how tumors are able to rebound after they appear to be completely wiped out by chemotherapy. One theory has been that because not all cells within a tumor are the same at the genetic level--a condition called tumor heterogeneity--a small subset of cells are able to resist treatment and begin growing again. Another theory involves the idea of tumor stem cells--that some of the cells within a tumor have special properties that allow them to re-form a tumor after chemotherapy has been given.

The idea that senescence is involved does not replace these other theories. In fact, it could provide new insight into explaining these other processes, Dr. Melnick said.

In the study, the researchers found that when AML cells were exposed to chemotherapy, a subset of the cells went into a state of hibernation, or senescence, while at the same time assuming a condition that looked very much like inflammation. They looked similar to cells that have undergone an injury and need to promote wound healing--shutting down the majority of their functions while recruiting immune cells to nurse them back to health.

"These characteristics are also commonly seen in developing embryos that temporarily shut down their growth due to lack of nutrition, a state called embryonic diapause," Dr. Melnick explained. "It's not a special process, but normal biological activity that's playing out in the context of tumors."

Further research revealed that this inflammatory senescent state was induced by a protein called ATR, suggesting that blocking ATR could be a way to prevent cancer cells from adopting this condition. The investigators tested this hypothesis in the lab and confirmed that giving leukemia cells an ATR inhibitor before chemotherapy prevented them from entering senescence, thereby allowing chemotherapy to kill all of the cells.

Importantly, studies published at the same time from two other groups reported that the role of senescence is important not just for AML, but for recurrent cases of breast cancer, prostate cancer and gastrointestinal cancers as well. Dr. Melnick was a contributor to one of those other studies.

Dr. Melnick and his colleagues are now working with companies that make ATR inhibitors to find a way to translate these findings to the clinic. However, much more research is needed, because many questions remain about when and how ATR inhibitors would need to be given.

"Timing will be very critical," he said. "We still have a lot to work out in the laboratory before we can study this in patients."

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Dr. Cihangir Duy, a former postdoctoral fellow in Dr. Melnick's lab, was the study's first author. Dr. Duy now leads his own lab at Fox Chase Cancer Center in Philadelphia.

Dr. Ari Melnick has been a paid consultant for KDAC Therapeutics, Epizyme, and Constellation Pharmaceuticals.

Breast cancer: The risks of brominated flame retardants

Brominated flame retardants may lead to early mammary gland development

INSTITUT NATIONAL DE LA RECHERCHE SCIENTIFIQUE - INRS QUEBEC, CA 

Research News

 

IMAGE: MAMMARY GLAND OF A PREPUBESCENT FEMALE RAT STAINED TO SEE ITS DEVELOPMENT. view more 

CREDIT: ISABELLE PLANTE (INRS)

Brominated flame retardants (BFRs) are found in furniture, electronics, and kitchenware to slow the spread of flames in the event of a fire. However, it has been shown that these molecules may lead to early mammary gland development, which is linked to an increased risk of breast cancer. The study on the subject by Professor Isabelle Plante from the Institut national de la recherche scientifique (INRS) made the cover of the February issue of the journal Toxicological Sciences.

Part of the flame retardants are considered to be endocrine disruptors, i.e. they interfere with the hormonal system. Since they are not directly bound to the material in which they are added, the molecules escape easily. They are then found in house dust, air and food.

This exposure can cause problems for mammary glands because their development is highly regulated by hormones. "BFRs pose a significant risk, particularly during sensitive periods, from intrauterine life to puberty and during pregnancy," says Professor Plante, co-director of the Intersectoral Centre for Endocrine Disruptor Analysis and environmental toxicologist. Endocrine disruptors, such as BFRs, can mimic hormones and cause cells to respond inappropriately.

The effects of environmental exposure

In their experiments, the research team exposed female rodents to a mixture of BFRs, similar to that found in house dust, prior to mating, during gestation and during lactation. Biologists were able to observe the effects on the offspring at two stages of development and on the mothers.

In pre-pubertal rats, the team noted early development of mammary glands. For pubescent rats, the results, published in 2019, showed a deregulation of communication between cells. Similar consequences were observed in female genitors in a 2017 study. All of these effects are associated with an increased risk of breast cancer.

Professor Isabelle Plante points out that peaks in human exposure to BFRs have been observed in the early 2000s. "Young women exposed to BFRs in utero and through breastfeeding are now in the early stages of fertility. Their mothers are in their fifties, a period of increased risk for breast cancer," says Professor Plante. This is why the team is currently studying endocrine disruptors related to a predisposition to breast cancer, funded by the Breast Cancer Foundation and the Cancer Research Society.

Debate over legislation

In all three studies, most of the effects were observed when subjects were exposed to the lowest dose, from dust, and not the higher doses. This observation raises questions about the current legislation for endocrine disruptors. "To evaluate the "safe" dose, experts give an increasing dose and then, when they observe an effect, identify it as the maximum dose. With endocrine disruptors, the long-term consequences would be caused by lower doses" reports Professor Plante.

Although counter-intuitive, this observation comes from the fact that high doses trigger a toxic response in the cells. When the body is exposed to lower doses, similar to the concentration of hormones in our body, the consequences rather consist in the deregulation of the hormonal system.

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About the study

The article "In Utero and Lactational Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Induces a Premature Development of the Mammary Glands", by Rita-Josiane Gouesse, Elham Dianati, Alec McDermott, Michael G Wade, Barbara Hales, Bernard Robaire and Isabelle Plante, has been published in the journal Toxicological Sciences. The study received support from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes of Health Research (CIHR) and Health Canada.

About INRS

INRS is a university dedicated exclusively to graduate level research and training. Since its creation in 1969, INRS has played an active role in Quebec's economic, social, and cultural development and is ranked first for research intensity in Quebec and in Canada. INRS is made up of four interdisciplinary research and training centres in Quebec City, Montreal, Laval, and Varennes, with expertise in strategic sectors: Eau Terre Environnement, Énergie Matériaux Télécommunications, Urbanisation Culture Société, and Armand-Frappier Santé Biotechnologie. The INRS community includes more than 1,500 students, postdoctoral fellows, faculty members, and staff.

Source :

Audrey-Maude Vézina
Service des communications de l'INRS
418 254-2156
audrey-maude.vezina@inrs.ca

Sea-level rise drives wastewater leakage to coastal waters

UNIVERSITY OF HAWAII AT MANOA

Research News

 

IMAGE: HIGH TIDE NUISANCE FLOODING IN MĀPUNAPUNA IS A HAZARD TO VEHICULAR AND PEDESTRIAN TRAFFIC. view more 

CREDIT: TRISTA MCKENZIE

When people think of sea level rise, they usually think of coastal erosion. However, recent computer modeling studies indicate that coastal wastewater infrastructure, which includes sewer lines and cesspools, is likely to flood with groundwater as sea-level rises.

A new study, published by University of Hawai'i (UH) at Mānoa earth scientists, is the first to provide direct evidence that tidally-driven groundwater inundation of wastewater infrastructure is occurring today in urban Honolulu, Hawai'i. The study shows that higher ocean water levels are leading to wastewater entering storm drains and the coastal ocean--creating negative impacts to coastal water quality and ecological health.

The study was led by postdoctoral researcher Trista McKenzie and co-authored by UH Sea Grant coastal geologist Shellie Habel and Henrietta Dulai, advisor and associate professor in the UH Mānoa School of Ocean and Earth Science and Technology (SOEST). The team assessed coastal ocean water and storm drain water in low-lying areas during spring tides, which serve as an approximation of future sea levels.

To understand the connection between wastewater infrastructure, groundwater and the coastal ocean, the researchers used chemical tracers to detect groundwater discharge and wastewater present at each site. Radon is a naturally occurring gas that reliably indicates the presence of groundwater, while wastewater can be detected by measuring specific organic contaminants from human sources, such as caffeine and certain antibiotics.

"Our results confirm that indeed, both groundwater inundation and wastewater discharge to the coast and storm drains are occurring today and that it is tidally-influenced," said McKenzie. "While the results were predicted, I was surprised how prevalent the evidence for these processes and the scale of it."

In low-lying inland areas, storm drains can overflow every spring tide. This study demonstrated that at the same time wastewater from compromised infrastructure also discharges into storm drains. During high tides, storm drains are becoming channels for untreated wastewater to flood streets and sidewalks. In addition to impeding traffic, including access by emergency vehicles, this flooding of contaminated water also poses a risk to human health.

The team also found evidence that many of the human-derived contaminants were in concentrations that pose a high risk to aquatic organisms. This has negative consequences to coastal organisms where the groundwater and storm drains discharge.

"Many people may think of sea-level rise as a future problem, but in fact, we are already seeing the effects today," said McKenzie. "Further, these threats to human health, ocean ecosystems and the wastewater infrastructure are expected to occur with even greater frequency and magnitude in the future."

This project demonstrates that actions to mitigate the impact from sea-level rise to coastal wastewater infrastructure in Honolulu are no longer proactive but are instead critical to addressing current issues. Through its multi-partner effort, the Hawai'i State Climate Commission also raises awareness around the variety of impacts of sea level rise, including those highlighted by this study.

"Coastal municipalities should pursue mitigation strategies that account for increased connectivity between wastewater infrastructure and recreational and drinking water resources," said McKenzie. "We need to consider infrastructure that minimizes flooding opportunities and contact with contaminated water; and decreases the number of contaminant sources, such as installation of one-way valves for storm drains, decommissioning cesspools, monitoring defective sewer lines, and construction of raised walkways and streets."

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This study led to McKenzie being awarded the L&O Letters Early Career Publication Honor, given in recognition of the high quality of research conducted by excellent early career scientists.

BYE BYE BOLSONARO
For Brazil's Bolsonaro, Lula's return a double-edged sword

AFP 

3/12/2021

There were whispers when Brazilian leftist Luiz Inacio Lula da Silva made his political comeback this week that President Jair Bolsonaro was licking his chops, seeing an easy foil for his reelection bid.

© Miguel SCHINCARIOL Brazilian former president (2003-2011) Luiz Inacio Lula da Silva, waves as he arrives for a press conference in Sao Bernardo do Campo, in metropolitan Sao Paulo, Brazil, on March 10, 2021

But it only took two days for the far-right leader to start looking worried at the prospect of a heavyweight showdown years in the making: Bolsonaro vs. Lula in 2022.

The first sign of concern in the president's camp was an extremely rare sighting: Bolsonaro, who has regularly flouted expert advice on Covid-19, dutifully wearing a face mask Wednesday.

Speaking at an official ceremony, he defended his handling of the pandemic, which has claimed 273,000 lives in hard-hit Brazil.

"This is a government of seriousness and responsibility," Bolsonaro said, signing a bill to accelerate vaccine purchases -- the same vaccines he had vowed not to take himself and joked could "turn you into an alligator."

© EVARISTO SA Brazilian President Jair Bolsonaro coughs at the Planalto Palace in Brasilia, on March 10, 2021

The about-face came hours after Lula tore into Bolsonaro's record on the pandemic.

"Brazil has no government," he said, attacking Bolsonaro's "imbecile" handling of Covid-19 in a speech marking his return to politics.

Lula, the alternately revered and reviled leftist who led Brazil through an economic boom from 2003 to 2010, regained the right to run for office Monday when a Supreme Court judge annulled his corruption convictions on procedural grounds, sending them to another court.

That put the charismatic steelworker-turned-president back in the political game for the first time since 2018, when he was jailed for taking bribes from companies seeking juicy contracts with state oil giant Petrobras.

He spent 18 months in prison and was barred from the 2018 presidential election, in which he had been the front-runner -- and which Bolsonaro ultimately won, riding a wave of outrage with Lula and his Workers' Party (PT).

Lula, who claims he is innocent, wasted no time making what looked very much like a stump speech -- though he stopped short of formally announcing his candidacy for October 2022.

A key question now for Latin America's most-populous country and largest economy is how its president will play the new political gameboard.

- Battle of extremes? -

On the one hand, Lula's return to politics looks like fuel to the fire for Bolsonaro, the divisive polemicist dubbed the "Tropical Trump."

"Bolsonaro is a politician forged in the flames of confrontation. He has to have an enemy. He was dreaming of Lula's return to the ring," said political scientist Marcio Coimbra of the Mackenzie School in Brasilia.

Many Brazilians are fearing a campaign of polarizing extremes, at a time when the deeply divided country is already suffering from the pandemic and its economic fallout.

Bolsonaro, 65, let fly some of his trademark invective Thursday, calling Lula, 75, a "convict" and "piece of decaying meat" in a live Facebook video.

But if his first reactions are any indication, Lula's return could force Bolsonaro to move toward the center.

More than halfway into his term, Bolsonaro's hardline, polarizing style has given him few concrete achievements to boast.

And like Trump, his political role model, he will no longer be able to run as the outsider arriving to drain the swamp.

"Bolsonaro isn't a novelty any more," said law professor Michael Mohallem of the Getulio Vargas Foundation.

If the race goes to a Bolsonaro-Lula runoff, voters in the middle -- many of whom dislike both -- would likely lean Lula if the elections were today, he said.

"Bolsonaro is the one who looks like a radical," he told AFP.

Lula, who presented himself as a market-friendly, Covid-concerned moderate in Wednesday's speech, "looks like a mature, relatively reasonable politician by comparison," Mohallem said.

Bolsonaro's future handling of the pandemic could be a weathervane.

Sensitive to complaints from the business sector about the economic cost of Brazil's badly delayed immunization campaign, he looks poised to abandon his anti-vaccine rhetoric.

His senator son, Flavio, sought to rally Bolsonaro supporters on social media this week to republish a picture of the president with the caption, "the vaccine is our weapon."

"You don't win votes by being against the vaccine," said Mohallem.

"It might be easier for (Bolsonaro) to look like a flip-flopper than to pay the political price of that."

- Desperate for 'middle way' -

The latest twist has left some Brazilians longing for a third option -- and less-polarized politics.

Newspaper Estado de Sao Paulo called in an editorial for political, business and civil society leaders to settle on a candidate that "can speak to voters who are tired of both Lula's corruption and Bolsonaro's craziness."

But with more than a half-dozen lesser-known candidates jockeying for the centrist vote, for now Brazil 2022 is looking like a clash of the titans.

Barring a new surprise from the judiciary, of course.

jhb/mdl

Test drilling for oil in Namibia’s Okavango region poses toxic risk

The Canadian oil and gas company ReconAfrica began exploratory drilling in Namibia upstream of the wildlife-rich Okavango Delta in January. 

According to the company’s aerial imagery and an independent review, they don’t appear to have taken what experts say is an environmentally responsible measure to protect the local water supply from contamination.

© Photograph by Danita Delimont, Alamy Stock Photo Botswana. Okavango Delta. Khwai concession. Pack of African wild dogs (Lycaon pictus) looking out for prey.

Jeffrey Barbee 

3/12/2021

Namibia is a water-scarce country, and when news of the company’s project became more widespread, communities expressed concern that contaminants from drilling would seep into shallow aquifers that supply drinking water and irrigation for crops.

Conservationists also worry that contamination from the test drilling could affect wildlife in the vicinity—elephants, Temminck’s ground pangolins, African wild dogs, martial eagles—and in the UNESCO-recognized Okavango Delta some 160 miles downstream.

A large waste, or reserve, pit next to the first test well appears in a video that ReconAfrica posted on its website on January 10. Such pits are for storing the mud, fluids, and other materials—which may contain dangerous chemicals or be hypersaline—that come up when drilling for oil or natural gas. In British Columbia, Canada, where ReconAfrica is based, it’s standard industry practice to line these pits with an impermeable barrier that prevents chemicals from seeping into the earth and groundwater.\

© Photograph by John Grobler tktk

ReconAfrica spokesperson Claire Preece told National Geographic in October 2020 that drill cuttings would “be managed in lined pits.” She also said that “ReconAfrica follows Namibian regulations and policies as well as international best practices.” According to Namibian law, the company must “control the flow and prevent the waste, escape or spilling” of petroleum, drilling fluid, water or any other substance from the well.

In the company’s video, no lining is visible.

Namibian journalist John Grobler, who visited the site on January 23, confirmed to National Geographic that the reserve pit was unlined and had liquid pooling in it.

“From an environmental aspect this is grossly unacceptable, and from a social aspect [it] is reckless and disgraceful,” says Jan Arkert, a consulting engineering geologist based in Uniondale, South Africa, who has worked for decades on drilling-related projects. “The communities are totally dependent on groundwater for domestic and agricultural purposes, and any contamination to the aquifer will be all but impossible to contain and clean up.

Arkert says that if the company chose to line the pit now, after drilling has started, it would be complicated. It would involve multiple steps, including removing the waste already there and disposing of it at a suitable facility, preparing the underlying gravel layer to ensure it won’t puncture the liner, and then installing the liner itself, which might have to be imported. Each step, Arkert says, is time consuming and likely would take at least three to four weeks.

“It looks to me like drilling fluids from the rig are being discharged into the unlined reserve pit,” says Matt Totten, Jr., a former exploration geologist for the oil and gas industry who has worked on projects in the United States, after he examined ReconAfrica’s video and still images. “Notice the dark brown discolored areas in the pond next to the rig where drilling fluids would be discharged.”

After reviewing another aerial video from drill site published by the German news program VOX on March 4, Totten confirmed that the now very full pit still “appears unlined and likely filled with a mixture of rainwater and drilling fluids.”

ReconAfrica did not respond to multiple requests for comment about its reserve pit.

To get permission from the Namibian government to drill exploratory wells, ReconAfrica had to do an assessment of their environmental impacts. The company’s resulting report referred to a waste “pond” and noted that it would “scrape all waste that has collected in the pond and dispose of these and the pond lining at a suitable site.”

Arkert, who joined a Zoom conference on oil and gas development in Africa on February 17 hosted by the European Association of Geoscientists and Engineers, asked Scot Evans, the CEO of ReconAfrica, why the company didn’t line the pit.

Evans didn’t answer the question directly but said that in Canada the fluid “is used as fertilizer.” He added, “We are going to have a little experiment when we are done with the local [agriculture] people to introduce fertilizers to the community.”

According to Arkert, that answer “can only be described as bizarre,” because Evans is referring only to the drill fluid. But what’s particularly dangerous are naturally occurring compounds such as benzene, ethylene, toluene, and zylene, as well as radioactive water, which come to the surface if petroleum is discovered. The “brew that is stored in the unlined containment pond will be a cocktail of toxic liquid waste, fit only for disposal in a hazardous landfill site,” Arkert says.

Other experts agree. Water coming up the well when drilling into oil and gas formations “is typically saline, contains oil and grease, and can contain toxic organic and inorganic compounds, and naturally occurring radioactive materials,” says Surina Esterhuyse, a geohydrologist with the University of the Free State, in Bloemfontein, South Africa. Some of those chemicals have been proven to cause cancer, birth defects, and reproductive disorders in people, according to a 2016 study in the journal Environmental Health Perspectives.

According to a 2009 U.S. Fish and Wildlife Service report, reserve pits can contaminate farmland, streams, and drinking water sources and “can entrap and kill migratory birds and other wildlife.”

It is unclear what protocols ReconAfrica has followed for its first Namibian test well reserve pit to protect the area’s fragile ecosystem.


Wildlife Watch is an investigative reporting project between National Geographic Society and National Geographic Partners focusing on wildlife crime and exploitation. Read more Wildlife Watch stories here, and learn more about National Geographic Society’s nonprofit mission at nationalgeographic.org. Send tips, feedback, and story ideas to NGP.WildlifeWatch@natgeo.com.