thescientist--2020-08-04--Study: Test College Students for Coronavirus Every Two Days

As colleges prepare to open—or not open—their campuses to students for the upcoming school year , scientists have come up with a scenario they say could limit the spread of the coronavirus .
Testing every student every two days and quickly isolating those with positive results should avoid widespread SARS-CoV-2 infections on college campuses , whereas only testing students with symptoms would not , according to a modeling study published Friday ( July 31 ) in JAMA Network Open .
The researchers used an initial scenario with 5,000 students on campus , 10 of whom were carrying the coronavirus .
@ @ @ @ @ @ @ infects , the frequency of testing , and the sensitivity of the tests used—that is , how often they correctly identify a person as infected .
If students were tested each day with a test with a sensitivity of 70 percent , 162 would become infected over the course of an 80-day semester , the model projected ; testing every two days would result in 243 new infections .
In contrast , weekly testing would result in 1,840 new infections .
That sensitivity is on the low end for tests , but the @ @ @ @ @ @ @ than higher-quality versions .
Study coauthor A. David Paltiel tells The Washington Post that the frequency of testing is more important than its accuracy , because testing repeatedly would eventually identify positive cases .
He also notes that deciding not to reopen campuses , and instead have students stay home for the semester , is not without risk .
“ The problem doesn ’ t go away simply because you don ’ t reopen campus , ” he says .
In remarks to UPI , Paltiel recognizes that high-frequency testing of all students @ @ @ @ @ @ @ This sets a high bar—logistically , financially and behaviorally—that may be beyond the capacity of many universities , and everything that could go wrong has to go right to avert an outbreak , ” he tells the wire service .
“ However , any school that can not meet these minimum screening standards or maintain uncompromising control over good prevention practices has to ask itself if it has any business reopening.
” See “ Saliva Tests : How They Work and What They Bring to COVID-19 ” The modeling did not uncover any @ @ @ @ @ @ @ students displayed symptoms would contain the virus , and Paltiel tells CNN that doing so would be “ like a fire department that only responds to calls once they have verifiable evidence that the house has already burned to the ground.
” In a commentary accompanying the study , other researchers suggest that frequent testing may not be necessary if students test negative before being allowed back on campus and if multiple precautions are taken to stop the virus from getting onto campus or spreading once there , such as mask wearing and @ @ @ @ @ @ @ They estimate that with such measures and testing every four weeks , their college , Vassar , would only see 79 student infections out of 2,500 people over the course of a semester .
“ Thus , before diverting resources from other interventions to testing every 2 days , we should consider a broader perspective , ” they write .
“ The best-prepared campuses will implement a set of interlocking strategies that together aim , first , to reduce the influx of COVID-19 from outside and , second , to limit its spread @ @ @ @ @ @ @ Higher Education “ I ’ m a little bit distressed by how confident Vassar is to weed out infection by re-entry and to keep the students inside that walled garden and to regulate that behavior .
As someone with an engineering background , I think often about the fact that we build bridges not to withstand the weight we expect but to withstand the weight several times we expect .
”

If students were tested each day with a test with a sensitivity of 70 percent, 162 would become infected over the course of an...
The researchers used an initial scenario with 5,000 students on campus, 10 of whom were carrying the coronavirus. They varied how many people each student infects, the frequency of testing, and the sensitivity of the tests used—that is, how often they correctly identify a person as infected.
As colleges prepare to open—or not open—their campuses to students for the upcoming school year, scientists have come up with a scenario they say could limit the spread of the coronavirus. Testing every student every two days and quickly isolating those with positive results should avoid widespread SARS-CoV-2 infections on college campuses, whereas only testing students with symptoms would not, according to a modeling study published Friday (July 31) in JAMA Network Open .
Study coauthor A. David Paltiel tells The Washington Post that the frequency of testing is more important than its accuracy, because testing repeatedly would eventually identify positive cases. He also notes that deciding not to reopen campuses, and instead have students stay home for the semester, is not without risk. “The problem doesn’t go away simply because you don’t reopen campus,” he says.
In remarks to UPI, Paltiel recognizes that high-frequency testing of all students will be challenging to implement. “This sets a high bar—logistically, financially and behaviorally—that may be beyond the capacity of many universities, and everything that could go wrong has to go right to avert an outbreak,” he tells the wire service. “However, any school that cannot meet these minimum screening standards or maintain uncompromising control over good prevention practices has to ask itself if it has any business reopening.”
The modeling did not uncover any scenarios in which waiting to act until students displayed symptoms would contain the virus, and Paltiel tells CNN that doing so would be “like a fire department that only responds to calls once they have verifiable evidence that the house has already burned to the ground.”
In a commentary accompanying the study, other researchers suggest that frequent testing may not be necessary if students test negative before being allowed back on campus and if multiple precautions are taken to stop the virus from getting onto campus or spreading once there, such as mask wearing and social distancing and erecting physical barriers. They estimate that with such measures and testing every four weeks, their college, Vassar, would only see 79 student infections out of 2,500 people over the course of a semester. “Thus, before diverting resources from other interventions to testing every 2 days, we should consider a broader perspective,” they write. “The best-prepared campuses will implement a set of interlocking strategies that together aim, first, to reduce the influx of COVID-19 from outside and, second, to limit its spread once on campus.”


thescientist--2020-08-04--Most Members of Federal Fetal Tissue Ethics Panel Oppose Abortion

More than a year after the Department of Health and Human Services announced the creation of the National Institutes of Health Human Fetal Tissue Research Ethics Advisory Board , members of the committee convened for the first time on Friday ( July 31 ) to oversee the ethics of using fetal tissue in federally funded research .
Of the 15 committee members , appointed by President Donald Trump , 10 have a history of activism against abortion or fetal tissue use .
As Buzzfeed News reports , some researchers have voiced concerns that the panel could impair future research on @ @ @ @ @ @ @ and more .
The board ’ s purpose is to review research grant proposals that study human fetal tissue ( HFT ) and advise that they receive funding only if no adequate alternatives exist and that the acquisition and disposal of the material meet ethical guidelines .
Their recommendations will be passed along to Alex Azar , Secretary of the Department of Health and Human Services .
HFT is used to study many diseases , including HIV , diabetes , Parkinson ’ s disease , and others .
While the availability of HFT @ @ @ @ @ @ @ over the years , the Trump administration announced last summer that there would be new restrictions on obtaining biological material from abortions .
The committee chair is Paige Comstock Cunningham , an attorney with a doctorate in educational studies , Science reports .
Cunningham was the president of Americans United for Life , an anti-abortion organization , and has testified before Congress against research using fetal tissues .
Nine other members of the board have also made public anti-abortion or anti-contraceptive stances in the form of op-eds , Congressional testimonies , and drafting @ @ @ @ @ @ @ researchers , two pediatricians , an OB-GYN , an internist , and a professor of moral philosophy , according to Science .
Three of them are connected professionally to the Charlotte Lozier Institute , the research arm of the Susan B. Anthony List , which is “ an organization dedicated to electing candidates and pursuing policies that will reduce and ultimately end abortion , ” according to its website .
Four members of the board , a neonatologist and three researchers , have not opined publicly on the topic of fetal tissue research @ @ @ @ @ @ @ Restrictions on Fetal Tissue Research ” The final appointee is Lawrence Goldstein , a neuroscientist at the University of California , San Diego , who uses fetal cells in Alzheimer ’ s research and has publicly opposed undue restrictions on their use .
“ The fetal tissue that we ’ re talking about—if we don ’ t use it for research , it will be discarded , ” Goldstein told The Scientist earlier this year .
“ That ’ s the choice .
Discard the fetal tissue in the trash , or use @ @ @ @ @ @ @ for the first meeting involved 40 minutes of introductions and establishing procedures , 20 minutes of public comments , and five hours of closed-door discussions .
The long wait between the advisory board ’ s announcement and its actual creation has resulted in grant proposals growing stagnant , as the committee review became a requirement back on September 25 , 2019 .
This has already prevented some studies from occurring , Buzzfeed News reports .
Clarification ( August 4 ) : The text has been updated to reflect that the Charlotte Lozier Institute @ @ @ @ @ @ @ the Susan B. Anthony List .

The board’s purpose is to review research grant proposals that study human fetal tissue (HFT) and advise that they receive funding only if no adequate...
More than a year after the Department of Health and Human Services announced the creation of the National Institutes of Health Human Fetal Tissue Research Ethics Advisory Board , members of the committee convened for the first time on Friday (July 31) to oversee the ethics of using fetal tissue in federally funded research. Of the 15 committee members, appointed by President Donald Trump, 10 have a history of activism against abortion or fetal tissue use. As Buzzfeed News reports, some researchers have voiced concerns that the panel could impair future research on HIV, diabetes, COVID-19 vaccines, and more.
Update (August 19): The panel has rejected 13 of the 14 proposals it has considered thus far, The Washington Post reports.
More than a year after the Department of Health and Human Services announced the creation of the National Institutes of Health Human Fetal Tissue Research Ethics Advisory Board, members of the committee convened for the first time on Friday (July 31) to oversee the ethics of using fetal tissue in federally funded research. Of the 15 committee members, appointed by President Donald Trump, 10 have a history of activism against abortion or fetal tissue use. As Buzzfeed News reports, some researchers have voiced concerns that the panel could impair future research on HIV, diabetes, COVID-19 vaccines, and more.
The board’s purpose is to review research grant proposals that study human fetal tissue (HFT) and advise that they receive funding only if no adequate alternatives exist and that the acquisition and disposal of the material meet ethical guidelines. Their recommendations will be passed along to Alex Azar, Secretary of the Department of Health and Human Services.
HFT is used to study many diseases, including HIV, diabetes, Parkinson’s disease, and others. While the availability of HFT in biomedical research has waxed and waned over the years, the Trump administration announced last summer that there would be new restrictions on obtaining biological material from abortions.
The committee chair is Paige Comstock Cunningham, an attorney with a doctorate in educational studies, Science reports. Cunningham was the president of Americans United for Life, an anti-abortion organization, and has testified before Congress against research using fetal tissues.
Nine other members of the board have also made public anti-abortion or anti-contraceptive stances in the form of op-eds, Congressional testimonies, and drafting or promoting legislation. These include four researchers, two pediatricians, an OB-GYN, an internist, and a professor of moral philosophy, according to Science. Three of them are connected professionally to the Charlotte Lozier Institute, the research arm of the Susan B. Anthony List, which is “an organization dedicated to electing candidates and pursuing policies that will reduce and ultimately end abortion,” according to its website.
Four members of the board, a neonatologist and three researchers, have not opined publicly on the topic of fetal tissue research.
See “Scientists Grapple with US Restrictions on Fetal Tissue Research”
The final appointee is Lawrence Goldstein, a neuroscientist at the University of California, San Diego, who uses fetal cells in Alzheimer’s research and has publicly opposed undue restrictions on their use.
“The fetal tissue that we’re talking about—if we don’t use it for research, it will be discarded,” Goldstein told The Scientist earlier this year. “That’s the choice. Discard the fetal tissue in the trash, or use it for valuable research.”
The agenda for the first meeting involved 40 minutes of introductions and establishing procedures, 20 minutes of public comments, and five hours of closed-door discussions.
The long wait between the advisory board’s announcement and its actual creation has resulted in grant proposals growing stagnant, as the committee review became a requirement back on September 25, 2019. This has already prevented some studies from occurring, Buzzfeed News reports.
Clarification (August 4): The text has been updated to reflect that the Charlotte Lozier Institute is part of a larger organization, the Susan B. Anthony List.


thescientist--2020-08-03--The Intellifuge Rotor Calculator

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thescientist--2020-07-31--Children Often Carry More Coronavirus than Adults Do: Study

A new study is challenging the idea that younger children are somehow less susceptible to SARS-CoV-2 infection .
Children under the age of five have been found to carry just as much , if not more , coronavirus in their noses and throats than older kids or adults .
The results , published Thursday ( July 30 ) in JAMA Pediatrics , tested 145 people for evidence of the virus ’ s RNA .
After breaking their participants down into three age categories—younger children , older children , and adults—researchers found that the youngest group harbored between 10 times and @ @ @ @ @ @ @ two .
While the results can not speak to children ’ s ability to transmit the disease to others , they come at a time when schools nationwide weighing the risks of opening again in the fall .
“ The school situation is so complicated—there are many nuances beyond just the scientific one , ” Taylor Heald-Sargent , a pediatric infectious diseases expert at the Ann and Robert H. Lurie Children ’ s Hospital and the lead author on the study , tells The New York Times .
“ But one takeaway from @ @ @ @ @ @ @ assume that just because kids aren ’ t getting sick , or very sick , that they don ’ t have the virus.
” Heald-Sargent first became interested in the question of how COVID-19 affects children after receiving some strange test results—children ’ s swab samples were indicating a higher load of virus than adults , a counterintuitive observation given that kids appear far less likely to develop symptoms .
To determine the viral load in patients , doctors will take a standard nasopharyngeal swab and analyze it using a method called quantitative @ @ @ @ @ @ @ During each cycle of the qPCR , the initially small amount of viral genetic material doubles , leading to an exponential increase .
If there is more genetic material on the swab at the start , fewer cycles are needed to hit what is called a cycle threshold , or CT .
Samples collected from younger children generally had lower CTs , meaning they had more virus present in their samples from the beginning .
Heald-Sargent decided to look back over the several weeks , between late March and late April , to @ @ @ @ @ @ @ Originally , she tells the Times , “ it wasn ’ t even something we had set out to look for.
” Alongside her colleagues , Heald-Sargent analyzed samples taken from 145 people who had either visited drive-through testing sites in Chicago or visited local hospitals for any reason .
Because people with severe infections would be expected to have high viral loads , the team included only individuals with either mild or moderate symptoms .
In addition , they excluded people with asymptomatic infections , those who couldn ’ t pinpoint when @ @ @ @ @ @ @ who had experienced symptoms for more than a week before testing .
After dividing the participants into the three age groups—specifically , children under the age of five , children between five and 17 , and adults aged 18 to 65—the scientists saw that the low CT results were consistent in younger patients , while the CTs of older children and adults were more comparable to each other .
“ It definitely shows that kids do have levels of virus similar to and maybe even higher than adults , ” Heald-Sargent tells the @ @ @ @ @ @ @ with similar small studies from other countries .
In Germany , 47 children between one and 11 were found to have viral loads as high as those in adults .
Among 438 children in France , CT scores were similar between asymptomatic children and those with obvious symptoms , supporting the idea that children can harbor high amounts of the virus without becoming visibly ill. Alpana Waghmare , a specialist in pediatric infectious diseases at Seattle Children ’ s , says the results of this latest study are a welcome addition .
“ @ @ @ @ @ @ @ as robust as adults with Covid-19 so it ’ s really nice to have additional virologic data in pediatric patients , ” she tells CNN .
“ It ’ s not surprising to find higher viral loads in children .
I think the question of what that exactly means for transmission is still not clear.
” Researchers in South Korea recently published a study looking at disease transmission in children and young adults , finding that those between 10 and 19 years old transmitted the disease just as frequently as adults , although @ @ @ @ @ @ @ COVID-19 less frequently , CNN reports .
Scientists have also been turning to other diseases to assess how likely children are to transmit the coronavirus , but evidence is still lacking .
Rick Malley , a senior physician in pediatrics at Boston Children ’ s Hospital , tells NBC News “ we don ’ t have the evidence that children will play the same role with this virus as they do , say , with the flu virus , where it ’ s pretty clear that kids with flu are main drivers of @ @ @ @ @ @ @ likely the same could be true with COVID-19 .
“ Any grade-school teacher or pediatrician will tell you , [ young children ] are pretty effective little vectors of virus transmission , because we get sick a lot in the winter from these kids , ” she says to CNN .
“ I think looking at other viruses that are similar .
.
.
it would seem more likely that kids will be transmitting ” COVID-19 as well , she says , adding that further research will be needed to confirm it .

The results, published Thursday (July 30) in JAMA Pediatrics , tested 145 people for evidence of the virus’s RNA. After breaking their participants down into three age categories—younger children, older children, and adults—researchers found that the youngest group harbored between 10 times and 100 times more virus than the other two. While the results cannot speak to children’s ability to transmit the disease to others, they come at a time when schools nationwide weighing the risks of opening again in the fall.
A new study is challenging the idea that younger children are somehow less susceptible to SARS-CoV-2 infection. Children under the age of five have been found to carry just as much, if not more, coronavirus in their noses and throats than older kids or adults.
Heald-Sargent first became interested in the question of how COVID-19 affects children after receiving some strange test results—children’s swab samples were indicating a higher load of virus than adults, a counterintuitive observation given that kids appear far less likely to develop symptoms. To determine the viral load in patients, doctors will take a standard nasopharyngeal swab and analyze it using a method called quantitative polymerase chain reaction (qPCR). During each cycle of the qPCR, the initially small amount of viral genetic material doubles, leading to an exponential increase. If there is more genetic material on the swab at the start, fewer cycles are needed to hit what is called a cycle threshold, or CT.
Samples collected from younger children generally had lower CTs, meaning they had more virus present in their samples from the beginning. Heald-Sargent decided to look back over the several weeks, between late March and late April, to see how common this result was. Originally, she tells the Times, “it wasn’t even something we had set out to look for.”
Alongside her colleagues, Heald-Sargent analyzed samples taken from 145 people who had either visited drive-through testing sites in Chicago or visited local hospitals for any reason. Because people with severe infections would be expected to have high viral loads, the team included only individuals with either mild or moderate symptoms. In addition, they excluded people with asymptomatic infections, those who couldn’t pinpoint when their symptoms had started, and people who had experienced symptoms for more than a week before testing.
After dividing the participants into the three age groups—specifically, children under the age of five, children between five and 17, and adults aged 18 to 65—the scientists saw that the low CT results were consistent in younger patients, while the CTs of older children and adults were more comparable to each other. “It definitely shows that kids do have levels of virus similar to and maybe even higher than adults,” Heald-Sargent tells the Times.
The results are in line with similar small studies from other countries. In Germany, 47 children between one and 11 were found to have viral loads as high as those in adults. Among 438 children in France, CT scores were similar between asymptomatic children and those with obvious symptoms, supporting the idea that children can harbor high amounts of the virus without becoming visibly ill.
Alpana Waghmare, a specialist in pediatric infectious diseases at Seattle Children’s, says the results of this latest study are a welcome addition. “The data in pediatrics has not been as robust as adults with Covid-19 so it’s really nice to have additional virologic data in pediatric patients,” she tells CNN. “It’s not surprising to find higher viral loads in children. I think the question of what that exactly means for transmission is still not clear.”
Researchers in South Korea recently published a study looking at disease transmission in children and young adults, finding that those between 10 and 19 years old transmitted the disease just as frequently as adults, although children under nine were found to transmit COVID-19 less frequently, CNN reports.
Scientists have also been turning to other diseases to assess how likely children are to transmit the coronavirus, but evidence is still lacking. Rick Malley, a senior physician in pediatrics at Boston Children’s Hospital, tells NBC News , “we don’t have the evidence that children will play the same role with this virus as they do, say, with the flu virus, where it’s pretty clear that kids with flu are main drivers of spread.”
Heald-Sargent says it’s likely the same could be true with COVID-19. “Any grade-school teacher or pediatrician will tell you, [young children] are pretty effective little vectors of virus transmission, because we get sick a lot in the winter from these kids,” she says to CNN. “I think looking at other viruses that are similar . . . it would seem more likely that kids will be transmitting” COVID-19 as well, she says, adding that further research will be needed to confirm it.


thescientist--2020-07-31--Regulator of Mysterious Gut Antibodies Identified

ABOVE : Even in the absence of T cells , mice have antibody-producing plasma cells ( green ) in the walls of their intestines .
GRASSET ET AL.
, SCI IMMUNOL , 5 : EAAT7117 , 2020 In the gut wall , activated B cells ( also known as plasma cells ) are continuously making antibodies against intestinal microbes .
They do this with and without the help of T cells and , while much is understood about the T cell–dependent antibody production pathway , how the T cell–independent process is regulated was unclear .
Now , researchers have discovered @ @ @ @ @ @ @ production , reporting the finding in Science Immunology today ( July 31 ) .
However , the role of these antibodies in regulating the gut microbiome or host health remains elusive .
“ It 's an elegant scientific observation .
They nailed the pathway .
.
.
[ and ] their conclusions are pretty firm , ” says clinical immunologist Balfour Sartor of the University of North Carolina who was not involved in the research “ But the question is , what does it mean , what ’ s the biologic importance [ @ @ @ @ @ @ @ ” The lumen of the gut contains a multitude of food and microbial antigens that the host immune system continuously surveys to balance nutrient absorbance , tolerance of commensal bacteria , and protection against pathogens .
An essential feature of this surveillance is the continuous production , by gut-wall plasma cells , of immunoglobulin A ( IgA ) antibodies , which bind the assorted antigens and contribute to the appropriate response .
While the production of some of these antibodies requires T cells—which are primed by the antigens before activating the B cells—some @ @ @ @ @ @ @ , says clinical immunologist Emilie Grasset of Mount Sinai School of Medicine in New York who led the study .
In mice , she explains , “ even without T cells the antibodies are able to bind the bacteria.
” Such T cell–independent antibody production has been observed systemically in mice where it was found to require a B cell receptor called transmembrane activator and CAML interactor , or TACI ( pronounced tah-see , not tah-key ) that binds cytokines produced in response to foreign antigens and leads to activation of the B @ @ @ @ @ @ @ regulate T cell–independent antibody production in the gut , Grasset and colleagues studied mice genetically engineered to lack either TACI , T cells , or both TACI and T cells , as well as wildtype animals .
In the colons and small intestines of mice that lacked T cells , antibody-producing plasma cells “ were still there , ” says Grasset .
However , in the mice lacking both T cells and TACI , “ the cells were missing.
” Moreover , she explains , the abundance of immunoglobulin-bound bacteria was significantly reduced @ @ @ @ @ @ @ cells and TACI compared with those that lacked only T cells .
Together , these results confirm T cell–independent antibodies are produced in the gut , bind to bacteria , and their production requires TACI .
“ They have definitively shown a receptor that is important for the antibody responses in a T cell–independent fashion , [ which ] is something that the field has wondered about for a long time , ” says commensal bacteria researcher June Round of the University of Utah who was not involved in the work .
But @ @ @ @ @ @ @ , is , “ why do we have a T cell–independent response ?
” In attempts to answer that question , Grasset and colleagues searched for differences between TACI-lacking and TACI-sufficient mice .
They examined the sequences of the antibodies that the animals produced , the taxonomical composition of their gut microbiota , and the ability of their gut microbes to penetrate their gut walls .
But , in short , they found no significant differences in any of these aspects between the animals with and without TACI .
“ I was a @ @ @ @ @ @ @ deletion of the receptor ] didn ’ t change the types of microbes that live in the gut , ” says Round .
It ’ s possible that differences in antibody production , or immune response , may become apparent between mice with and without TACI if the animals were , for example , challenged with pathogenic bacteria , or made germ-free and then given specific commensal microbes , says Round .
She also suggests that transcriptome analysis of the gut bacteria taken from mice with and without TACI might reveal differences in @ @ @ @ @ @ @ –independent antibody interactions .
For now , though , the function of T cell–independent antibodies “ is an open question , ” says Grasset , “ we know they bind [ bacteria ] for sure , so they must be doing something , ” E.K .
Grasset et al.
, “ Gut T cell–independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells.
” Sci Immunol , 5 : eaat7117 , 2020 .
Correction ( August 3 ) : A quote from Grasset in the third paragraph incorrectly @ @ @ @ @ @ @ ’ t need T cells , rather , some antibodies don ’ t require T cells for production .
The Scientist regrets the error .

“It's an elegant scientific observation. They nailed the pathway . . . [and] their conclusions are pretty firm,” says clinical immunologist Balfour Sartor of the University of North Carolina who was not involved in...
In the gut wall, activated B cells (also known as plasma cells) are continuously making antibodies against intestinal microbes. They do this with and without the help of T cells and, while much is understood about the T cell–dependent antibody production pathway, how the T cell–independent process is regulated was unclear. Now, researchers have discovered a master controller of T cell–independent antibody production, reporting the finding in Science Immunology today (July 31). However, the role of these antibodies in regulating the gut microbiome or host health remains elusive.
ABOVE: Even in the absence of T cells, mice have antibody-producing plasma cells (green) in the walls of their intestines. GRASSET ET AL., SCI IMMUNOL, 5:EAAT7117, 2020
The lumen of the gut contains a multitude of food and microbial antigens that the host immune system continuously surveys to balance nutrient absorbance, tolerance of commensal bacteria, and protection against pathogens. An essential feature of this surveillance is the continuous production, by gut-wall plasma cells, of immunoglobulin A (IgA) antibodies, which bind the assorted antigens and contribute to the appropriate response. While the production of some of these antibodies requires T cells—which are primed by the antigens before activating the B cells—some antibodies don’t need T cells, says clinical immunologist Emilie Grasset of Mount Sinai School of Medicine in New York who led the study. In mice, she explains, “even without T cells the antibodies are able to bind the bacteria.”
Such T cell–independent antibody production has been observed systemically in mice where it was found to require a B cell receptor called transmembrane activator and CAML interactor, or TACI (pronounced tah-see, not tah-key) that binds cytokines produced in response to foreign antigens and leads to activation of the B cell.
Hypothesizing that TACI might also regulate T cell–independent antibody production in the gut, Grasset and colleagues studied mice genetically engineered to lack either TACI, T cells, or both TACI and T cells, as well as wildtype animals.
In the colons and small intestines of mice that lacked T cells, antibody-producing plasma cells “were still there,” says Grasset. However, in the mice lacking both T cells and TACI, “the cells were missing.” Moreover, she explains, the abundance of immunoglobulin-bound bacteria was significantly reduced in the mice that lacked both T cells and TACI compared with those that lacked only T cells. Together, these results confirm T cell–independent antibodies are produced in the gut, bind to bacteria, and their production requires TACI.
“They have definitively shown a receptor that is important for the antibody responses in a T cell–independent fashion, [which] is something that the field has wondered about for a long time,” says commensal bacteria researcher June Round of the University of Utah who was not involved in the work. But the other big question, she says, is, “why do we have a T cell–independent response?”
In attempts to answer that question, Grasset and colleagues searched for differences between TACI-lacking and TACI-sufficient mice. They examined the sequences of the antibodies that the animals produced, the taxonomical composition of their gut microbiota, and the ability of their gut microbes to penetrate their gut walls. But, in short, they found no significant differences in any of these aspects between the animals with and without TACI.
“I was a little surprised, actually, that [deletion of the receptor] didn’t change the types of microbes that live in the gut,” says Round.
It’s possible that differences in antibody production, or immune response, may become apparent between mice with and without TACI if the animals were, for example, challenged with pathogenic bacteria, or made germ-free and then given specific commensal microbes, says Round. She also suggests that transcriptome analysis of the gut bacteria taken from mice with and without TACI might reveal differences in the effects of the T cell–dependent and –independent antibody interactions.
For now, though, the function of T cell–independent antibodies “is an open question,” says Grasset, “we know they bind [bacteria] for sure, so they must be doing something,”
E.K. Grasset et al., “Gut T cell–independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells.” Sci Immunol, 5:eaat7117, 2020.
Correction (August 3): A quote from Grasset in the third paragraph incorrectly stated that a majority of antibodies don’t need T cells, rather, some antibodies don’t require T cells for production. The Scientist regrets the error.


thescientist--2020-07-31--How Our Exhalations Help Spread Pathogens Such as SARS-CoV-2

Lydia Bourouiba first began thinking about how pathogens travel during the global SARS outbreak that began in November 2002 .
SARS , a close viral cousin of SARS-CoV-2 , the virus causing the current COVID-19 pandemic , leapt from person to person via contaminated surfaces , but even then there was discussion among epidemiologists that airborne transmission may be an understudied mechanism contributing to the spread of the virus .
As a physical mathematician with an interest in fluid dynamics and public health , Bourouiba knew that pathogens exist in fluids—in the body , in water , or in air—and @ @ @ @ @ @ @ fluids move through the world .
Despite what she calls the “ many gaps in our understanding ” of how diseases pass from person to person , these two points made her curious enough to pivot from a career in mathematics and physics to one in epidemiology .
Now , as director of the fluid dynamics of disease transmission laboratory at MIT , Bourouiba and her colleagues merge fluid dynamics and epidemiology to study the transmission of SARS-CoV-2 and other pathogens that dwell in respiratory fluids .
With more than 17 million COVID-19 @ @ @ @ @ @ @ , understanding how SARS-CoV-2 and other pathogens spread is critical .
Scientists around the world recently petitioned agencies such as the World Health Organization to acknowledge airborne transmission in the current pandemic , prompting the agency to admit that , at least indoors , it “ can not be ruled out.
” In her lab , Bourouiba uses a combination of theoretical approaches and experimental tools , such as flow visualization , high-speed imaging , and microscopy , to build a more holistic view of the air we exhale as dynamic and complex @ @ @ @ @ @ @ travel more than 20 feet from where we ’ re standing .
Her findings break away from the traditional study of airborne emissions as a dichotomy between large droplets and small aerosols .
Instead , she says , our coughs and sneezes project “ a continuum of droplet sizes , ” a fact that has important implications for modeling and assessing disease transmission .
The Scientist spoke with Bourouiba about the importance of studying pathogens transmitted through the air and how her work might inform our public health decisions during the COVID-19 pandemic @ @ @ @ @ @ @ physics of coughs and sneezes play into the transmission of diseases such as COVID-19 ?
Lydia Bourouiba : Right now , we believe [ SARS-CoV-2 is ] transmitted mostly through the respiratory tract .
The infection occurs in the respiratory tract and emissions from the tract are the propulsion mechanism of the virus into the environment and toward others .
It ’ s very important , therefore , to understand not only the distances but also the timescales of exposures .
The virus is never emitted in the air on its own .
@ @ @ @ @ @ @ secretion that is emitted from either breathing out , coughing , or sneezing .
In all cases , you ’ re creating a cloud , but the drop-size distribution and the energy of the gas will be different .
TS : What happens with our fluids when we do something like sneeze or cough ?
LB : The exhalation is very much like a cloud .
.
.
but it ’ s a [ cloud ] with a much higher momentum for coughs and sneezes .
It .
.
.
is moving around @ @ @ @ @ @ @ on top of a pot .
And it also contains this payload of droplets , like real clouds outside , [ with ] swelling and motion and turbulence inside .
The difference between different events [ e.g.
, talking , sneezing , coughing ] is simply the volumes [ of the clouds ] that are emitted , the timescales over which they ’ re emitted , and therefore also the energy or momentum that they have .
That momentum is what is driving the contamination range and exposures of others .
TS : @ @ @ @ @ @ @ being properly addressed during the pandemic ?
LB : Yes and no .
It has been discussed , and the paper that I published in the JAMA in March [ outlining the need for better models to track airborne transmission of COVID-19 ] has also generated a lot of discussion .
But I think that there ’ s still a very fragmented landscape of research and views about the topic that at this point really should be unified but are still not .
And it ’ s because the research hasn ’ t @ @ @ @ @ @ @ of pandemics , there ’ s a lot of different fields looking at these questions , and although cooperation and information transfer should be our goal , there hasn ’ t always been a dropping of the barriers between areas of research or even awareness of each other .
I don ’ t think we are at the point yet where we ’ ve seen a unified thrust forward that could bring all this together .
TS : Why is it so hard to study airborne diseases in particular ?
LB : A @ @ @ @ @ @ @ a time of crisis in a very rudimentary way .
Historically , there have been a lot of times where the questions should continue to be the focus after the pandemic to prepare for the next one [ but that often doesn ’ t happen ] .
It always leaves us in this vulnerable position of being in a reactive mode during a pandemic , which is not ideal to get down to the mechanisms of problems .
Research done in a rush is never really going to lead to deep insights .
@ @ @ @ @ @ @ protect ourselves and others from the risks associated with COVID-19 ?
LB : Wearing a mask , even if they ’ re not the hybrid respirators , is critical to minimize the range of that emission from one individual and to provide some level of protection to others .
But that does not necessarily replace the fact that we need to be careful about how close we are to others , how long we are in that space , how many individuals are in that space , and how the maintenance and protocols @ @ @ @ @ @ @ surfaces are being deployed .
Instead of thinking about one aspect , we really need to think holistically .
Editor ’ s note : The interview was edited for brevity .

Lydia Bourouiba first began thinking about how pathogens travel during the global SARS outbreak that began in November 2002. SARS, a close viral cousin of SARS-CoV-2, the virus causing the current COVID-19 pandemic, leapt from person to person via contaminated surfaces, but even then there was discussion among epidemiologists that airborne transmission may be an understudied mechanism contributing to the spread of the virus. As a physical mathematician with an interest in fluid dynamics and public health, Bourouiba knew that pathogens exist in fluids—in the body, in water, or in air—and she also knew a bit about how fluids move through the world. Despite what she calls the “many gaps in our understanding” of how diseases pass from person to person, these two points made her curious enough to pivot from a career in mathematics and physics to one in epidemiology.
Lydia Bourouiba LILLIE PAQUETTE, MIT SCHOOL OF ENGINEERING
In her lab, Bourouiba uses a combination of theoretical approaches and experimental tools, such as flow visualization, high-speed imaging, and microscopy, to build a more holistic view of the air we exhale as dynamic and complex “clouds” of droplets that can travel more than 20 feet from where we’re standing. Her findings break away from the traditional study of airborne emissions as a dichotomy between large droplets and small aerosols. Instead, she says, our coughs and sneezes project “a continuum of droplet sizes,” a fact that has important implications for modeling and assessing disease transmission.
The Scientist spoke with Bourouiba about the importance of studying pathogens transmitted through the air and how her work might inform our public health decisions during the COVID-19 pandemic.
The Scientist: How does the physics of coughs and sneezes play into the transmission of diseases such as COVID-19?
Lydia Bourouiba: Right now, we believe [SARS-CoV-2 is] transmitted mostly through the respiratory tract. The infection occurs in the respiratory tract and emissions from the tract are the propulsion mechanism of the virus into the environment and toward others. It’s very important, therefore, to understand not only the distances but also the timescales of exposures. The virus is never emitted in the air on its own. It’s always in the mucosalivary secretion that is emitted from either breathing out, coughing, or sneezing. In all cases, you’re creating a cloud, but the drop-size distribution and the energy of the gas will be different.
TS: What happens with our fluids when we do something like sneeze or cough?
LB: The exhalation is very much like a cloud . . . but it’s a [cloud] with a much higher momentum for coughs and sneezes. It . . . is moving around like you see when you have condensation on top of a pot. And it also contains this payload of droplets, like real clouds outside, [with] swelling and motion and turbulence inside.
See “Gesundheit”
The difference between different events [e.g., talking, sneezing, coughing] is simply the volumes [of the clouds] that are emitted, the timescales over which they’re emitted, and therefore also the energy or momentum that they have. That momentum is what is driving the contamination range and exposures of others.
TS: Do you feel that airborne transmission is being properly addressed during the pandemic?
LB: Yes and no. It has been discussed, and the paper that I published in the JAMA in March [outlining the need for better models to track airborne transmission of COVID-19] has also generated a lot of discussion. But I think that there’s still a very fragmented landscape of research and views about the topic that at this point really should be unified but are still not.
And it’s because the research hasn’t been done consistently. Particularly in terms of pandemics, there’s a lot of different fields looking at these questions, and although cooperation and information transfer should be our goal, there hasn’t always been a dropping of the barriers between areas of research or even awareness of each other. I don’t think we are at the point yet where we’ve seen a unified thrust forward that could bring all this together.
TS: Why is it so hard to study airborne diseases in particular?
LB: A lot of the information is gathered during a time of crisis in a very rudimentary way. Historically, there have been a lot of times where the questions should continue to be the focus after the pandemic to prepare for the next one [but that often doesn’t happen]. It always leaves us in this vulnerable position of being in a reactive mode during a pandemic, which is not ideal to get down to the mechanisms of problems. Research done in a rush is never really going to lead to deep insights.
TS: What can we do to protect ourselves and others from the risks associated with COVID-19?
LB: Wearing a mask, even if they’re not the hybrid respirators, is critical to minimize the range of that emission from one individual and to provide some level of protection to others. But that does not necessarily replace the fact that we need to be careful about how close we are to others, how long we are in that space, how many individuals are in that space, and how the maintenance and protocols of contamination for both the air and surfaces are being deployed. Instead of thinking about one aspect, we really need to think holistically.
Editor’s note: The interview was edited for brevity.


Gesundheit!

MIT ’ s Lydia Bourouiba used a high speed camera to record coughs and sneezes at a rate of up @ @ @ @ @ .
While previous work has described exhalations in terms of either large , fast-falling droplets @ @ @ @ @ , the videos reveal that sneezes are dynamic and turbulent clouds containing both air and @ @ @ @ @ .
These coughs and sneezes can travel up to 26 feet , far beyond the @ @ @ @ @ the Centers for Disease Control and Prevention .

VIDEO COURTESY OF PROF BOUROUIBA , MIT/JAMA NETWORK
MIT’s Lydia Bourouiba used a high speed camera to record coughs and sneezes at a rate of up to 2,000 frames per second. While previous work has described exhalations in terms of either large, fast-falling droplets or small, drifting aerosols, the videos reveal that sneezes are dynamic and turbulent clouds containing both air and mucosalivary droplets of many sizes. These coughs and sneezes can travel up to 26 feet, far beyond the 6-foot distancing rule recommended by the Centers for Disease Control and Prevention.
Read the full story.


thescientist--2020-07-30--For Mates to Fuse Bodies, Some Anglerfish Have Lost Immune Genes

ABOVE : A 75-mm-long Melanocetus johnsonii female with a 23.5-mm-long male attached to her belly EDITH A. WIDDER Krøyer ’ s deep-sea anglerfish , Ceratias holboelli , does not spawn , copulate , or do anything a fish would ordinarily do to mate .
Instead , the male—just a few inches long—clasps onto the comparatively gigantic female ’ s body and never lets go .
Slowly , his body morphs into hers , his cells becoming hers , including his testicles , which are used to make offspring .
As he vanishes , two individuals become one—taking the concept of @ @ @ @ @ @ @ sub-order of deep-sea anglerfish , composed of nearly 170 known species , arguably displays the most dramatic mating habits in the animal kingdom .
In some species , males only temporarily attach to females and then part ways .
In others , such as C. holboelli , males permanently “ fuse ” with females , or females absorb multiple males—in some cases up to eight at a time .
Among the many mysteries surrounding these deep-sea rendezvous—they were only captured on camera for the first time in 2018—is an immunological one .
In @ @ @ @ @ @ @ tissue from one individual into another would provoke a powerful immune response attacking the foreign cells .
Why don ’ t the female anglerfish , immunologically speaking , reject these parasitic males ?
A new genomic analysis of 13 anglerfish species published today ( July 30 ) in Science provides some clues .
The genomes of species that temporarily or permanently fuse with their mates have undergone radical alterations of key genes that underpin adaptive immunity—a branch of the immune system responsible for the rejection of foreign tissue—making some of them the first @ @ @ @ @ @ @ an adaptive immune system .
Over the course of evolution , changes in genes involved in antibody production and cytotoxic T cell responses may have paved the way for the animals ’ strange reproductive habits , while for scientists it raises questions about how the fish defend themselves against pathogens in the deep sea .
“ It ’ s quite shocking , ” remarks geneticist Elizabeth Murchison of the University of Cambridge who wasn ’ t involved in the study .
“ I suppose we shouldn ’ t have too many preconceptions about @ @ @ @ @ @ @ in nature .
Evolution produces all sorts of wacky outcomes , and this is one of them.
” Immunologist Thomas Boehm and his colleagues at the Max Planck Institute of Immunology and Epigenetics in Germany long wanted to know how some anglerfish species can form bodily fusions between individuals , and set out to do an analysis of the animals ’ genomes .
Biological samples from the deep sea are hard to come by , but with the help of ichthyologist Theodore Pietsch , an expert on deep-sea anglerfishes at the University of @ @ @ @ @ @ @ obtain tissue samples from several specimen collections .
Boehm and his colleagues sequenced the DNA from 31 specimens , representing 13 species of deep-sea anglerfish .
That included four species that mate by temporary attachment and six species that form permanent fusions—three of them in a one-to-one fashion , and three that have multiple males fuse with a single female .
The team also included three control species from other anglerfish groups in which males never attach to females .
The team examined a handful of well-characterized genes known to be key players @ @ @ @ @ @ @ , they looked at genes that encode the fishes ’ major histocompatibility complex ( MHC ) class I and II proteins , cell surface molecules that differ between individuals and enable T cells to distinguish the body ’ s own cells from foreign ones .
It ’ s the MHC class I receptors that drive cytotoxic T cells to attack foreign cells in tissue transplant settings .
Interestingly , the six permanently attaching species all showed unusual , significant alterations to their MHC genes , which were even more severe in the three @ @ @ @ @ @ @ each female .
The researchers also found alterations in the genes encoding receptors of the cytotoxic T cells that interact with the MHC class I proteins .
In all six permanent attachers , for instance , two genes that encode such receptors were entirely missing , suggesting that dismantling the cytotoxic reactivity of T cells might be necessary to allow different anglerfish individuals to mate .
Because antibodies directed against foreign tissue are also known to cause complications in patients during tissue transplants , the team also looked at certain genes that underpin @ @ @ @ @ @ @ genes seemed to be intact in most of the anglerfish species , they found that aicda , which plays an important role in creating specific antibodies , was effectively absent in all 10 species that form temporary or permanent attachments , whereas it was intact in the three control species .
Certain rag genes , which are also involved in antibody formation , had amassed deleterious mutations in species that mate as groups of males , whereas those genes were relatively intact in species that pair in a one-to-one fashion such as C. @ @ @ @ @ @ @ attachment between mates , the more extreme the changes to adaptive immunity genes appeared to be , the team notes .
While temporary attachment only seemed to require reduced antibody responses , permanent one-to-one fusions seemed to be associated also with the curtailing of cytotoxic T cell function .
In the case of multiple mates , this was marked by even more changes , such as the blunting of antibody responses , and the loss of rag genes .
To University College London immunologist and virologist Ariberto Fassati , who wasn ’ t @ @ @ @ @ @ @ are astonishing .
Many scientists assume that the immune system , once established , would evolve only in one direction , “ towards becoming more adaptive and more specific , ” Fassati says .
“ But this looks like you can actually lose arms of the adaptive immune system .
.
.
if evolutionary pressures are justified.
” To his knowledge , the deep-sea anglerfish species are the first instances of vertebrates having lost such a huge branch of their adaptive immunity .
In many other vertebrates , removing parts of the adaptive @ @ @ @ @ @ @ born with mutations in the rag gene , for instance , are severely sick or die quickly if they don ’ t receive treatment through a bone marrow transplantation , Boehm notes .
One reason why the adaptive immune system is thought to be so crucial is because many pathogens and parasites have learned to outsmart the less-specific , front-line innate immune defense , Fassati says .
For instance , many viruses , including the culprit of the ongoing COVID-19 pandemic , SARS-CoV-2 , can stem the body ’ s production of inflammation-driving @ @ @ @ @ @ @ innate immune defense , he adds .
The fact that some anglerfish are apparently getting along fine without a fully intact adaptive immune system is “ quite remarkable.
” This discovery raises the question of how they do manage to defend themselves from pathogens in the deep sea .
Boehm speculates that either the fish must have evolved some other immune system entirely , or perhaps they ’ ve found ways to ramp up their innate immune machinery to compensate for the lack of an adaptive immune response .
Maybe they could achieve @ @ @ @ @ @ @ speculates , placing their bodies on constant alert and making it harder for viruses and other pathogens to establish infections .
To prove that , he ’ d need fresh tissue where he could examine gene expression .
“ I ’ m desperately looking forward to obtaining animals where I could extract RNA and look for expression levels of these .
.
.
interferon-related genes , ” he says .
Finding out how some anglerfish do cope after losing adaptive immunity could be useful in finding treatments for immunodeficient patients , he adds @ @ @ @ @ @ @ pose a chicken-or-egg dilemma : which came first , the modifications to the genetic architecture underpinning adaptive immunity or the fusion mating strategy ?
One of the species he examined may offer a clue .
Gigantactis vanhoeffeni is thought to mate through temporary attachment , yet it shows some of the same alterations to immune genes as permanently attaching species .
Boehm says he thinks G. vanhoeffeni could possibly be “ en route to permanent attachment ” evolutionarily .
“ It seems that some changes to the immune genome have to occur before @ @ @ @ @ @ @ .
It seems that there is some as yet unknown evolutionary pressure of some sort that [ first ] causes these genes to go extinct or defunct.
” Gil Rosenthal , an evolutionary biologist at Texas A & M University , says he wonders what those evolutionary pressures could be .
Deep-sea anglerfish are extremely sexually dimorphic , he notes in an email to The Scientist .
“ Females are these nightmarish light-bearing fanged monsters , and males are tiny little things with a huge testis and a huge nose.
” The females @ @ @ @ @ @ @ , so it ’ s likely that the males spend a lot of time looking for them , he explains .
When a male finally finds a female , it would be in its interest to stick close .
If it happens that the female has conflicting interests—such as eating the males—it could set up the fish for “ sexual conflict.
” That situation could somehow lead to a genomic tug-of-war over the immune system , Rosenthal speculates .
“ I wouldn ’ t be surprised if some of the wreckage of the @ @ @ @ @ @ @ It wouldn ’ t be the first example of a trade-off between sexual behavior and immune system function , he adds , noting that in vertebrates , testosterone can depress immune system function and enhance male sexual displays .
However , “ that so much of it is shut down or remodeled in [ deep-sea anglerfish ] is just wild !
” To Rosenthal and Murchison , the results underscore how the genomics revolution has enabled researchers to venture beyond well-understood model organisms in labs and explore the different adaptations of life on @ @ @ @ @ @ @ much to be learned about not just immunity , but all of biology , by exploring evolutionarily divergent lineages , ” Murchison says .
“ And you never really know what you ’ re going to find because nature is so broad and diverse and there ’ s so much adaptation to very specialized niches .
”

The sub-order of deep-sea anglerfish, composed of nearly 170 known species, arguably displays the most dramatic mating habits in the animal kingdom. In some species, males only temporarily attach to females and then part ways. In others, such as C. holboelli, males permanently “fuse” with females, or females absorb multiple males—in some cases up to eight at a time.
Krøyer’s deep-sea anglerfish, Ceratias holboelli, does not spawn, copulate, or do anything a fish would ordinarily do to mate. Instead, the male—just a few inches long—clasps onto the comparatively gigantic female’s body and never lets go. Slowly, his body morphs into hers, his cells becoming hers, including his testicles, which are used to make offspring. As he vanishes, two individuals become one—taking the concept of monogamy to a new level.
A new genomic analysis of 13 anglerfish species published today (July 30) in Science provides some clues. The genomes of species that temporarily or permanently fuse with their mates have undergone radical alterations of key genes that underpin adaptive immunity—a branch of the immune system responsible for the rejection of foreign tissue—making some of them the first known instances of vertebrates that effectively lack an adaptive immune system. Over the course of evolution, changes in genes involved in antibody production and cytotoxic T cell responses may have paved the way for the animals’ strange reproductive habits, while for scientists it raises questions about how the fish defend themselves against pathogens in the deep sea.
“It’s quite shocking,” remarks geneticist Elizabeth Murchison of the University of Cambridge who wasn’t involved in the study. “I suppose we shouldn’t have too many preconceptions about what is and isn’t possible in nature. Evolution produces all sorts of wacky outcomes, and this is one of them.”
Immunologist Thomas Boehm and his colleagues at the Max Planck Institute of Immunology and Epigenetics in Germany long wanted to know how some anglerfish species can form bodily fusions between individuals, and set out to do an analysis of the animals’ genomes. Biological samples from the deep sea are hard to come by, but with the help of ichthyologist Theodore Pietsch, an expert on deep-sea anglerfishes at the University of Washington, the team was able to obtain tissue samples from several specimen collections.
Boehm and his colleagues sequenced the DNA from 31 specimens, representing 13 species of deep-sea anglerfish. That included four species that mate by temporary attachment and six species that form permanent fusions—three of them in a one-to-one fashion, and three that have multiple males fuse with a single female. The team also included three control species from other anglerfish groups in which males never attach to females.
The team examined a handful of well-characterized genes known to be key players in the adaptive immune response. First, they looked at genes that encode the fishes’ major histocompatibility complex (MHC) class I and II proteins, cell surface molecules that differ between individuals and enable T cells to distinguish the body’s own cells from foreign ones. It’s the MHC class I receptors that drive cytotoxic T cells to attack foreign cells in tissue transplant settings.
Interestingly, the six permanently attaching species all showed unusual, significant alterations to their MHC genes, which were even more severe in the three species in which multiple males fuse with each female. The researchers also found alterations in the genes encoding receptors of the cytotoxic T cells that interact with the MHC class I proteins. In all six permanent attachers, for instance, two genes that encode such receptors were entirely missing, suggesting that dismantling the cytotoxic reactivity of T cells might be necessary to allow different anglerfish individuals to mate.
A 46-mm-long female Photocorynus spiniceps with 6.2-mm-long parasitic male fused to her back Theodore W. Pietsch, University of Washington
Because antibodies directed against foreign tissue are also known to cause complications in patients during tissue transplants, the team also looked at certain genes that underpin antibody generation. Although many of these genes seemed to be intact in most of the anglerfish species, they found that aicda, which plays an important role in creating specific antibodies, was effectively absent in all 10 species that form temporary or permanent attachments, whereas it was intact in the three control species. Certain rag genes, which are also involved in antibody formation, had amassed deleterious mutations in species that mate as groups of males, whereas those genes were relatively intact in species that pair in a one-to-one fashion such as C. holboelli.
Overall, the more extreme attachment between mates, the more extreme the changes to adaptive immunity genes appeared to be, the team notes. While temporary attachment only seemed to require reduced antibody responses, permanent one-to-one fusions seemed to be associated also with the curtailing of cytotoxic T cell function. In the case of multiple mates, this was marked by even more changes, such as the blunting of antibody responses, and the loss of rag genes.
To University College London immunologist and virologist Ariberto Fassati, who wasn’t involved in the study, the results are astonishing. Many scientists assume that the immune system, once established, would evolve only in one direction, “towards becoming more adaptive and more specific,” Fassati says. “But this looks like you can actually lose arms of the adaptive immune system . . . if evolutionary pressures are justified.” To his knowledge, the deep-sea anglerfish species are the first instances of vertebrates having lost such a huge branch of their adaptive immunity.
In many other vertebrates, removing parts of the adaptive immune system has catastrophic consequences. Babies born with mutations in the rag gene, for instance, are severely sick or die quickly if they don’t receive treatment through a bone marrow transplantation, Boehm notes.
One reason why the adaptive immune system is thought to be so crucial is because many pathogens and parasites have learned to outsmart the less-specific, front-line innate immune defense, Fassati says. For instance, many viruses, including the culprit of the ongoing COVID-19 pandemic, SARS-CoV-2, can stem the body’s production of inflammation-driving interferons, which are part of the innate immune defense, he adds. The fact that some anglerfish are apparently getting along fine without a fully intact adaptive immune system is “quite remarkable.”
This discovery raises the question of how they do manage to defend themselves from pathogens in the deep sea. Boehm speculates that either the fish must have evolved some other immune system entirely, or perhaps they’ve found ways to ramp up their innate immune machinery to compensate for the lack of an adaptive immune response. Maybe they could achieve this by continuously expressing interferons, he speculates, placing their bodies on constant alert and making it harder for viruses and other pathogens to establish infections. To prove that, he’d need fresh tissue where he could examine gene expression.
“I’m desperately looking forward to obtaining animals where I could extract RNA and look for expression levels of these . . . interferon-related genes,” he says. Finding out how some anglerfish do cope after losing adaptive immunity could be useful in finding treatments for immunodeficient patients, he adds.
To him, the results also pose a chicken-or-egg dilemma: which came first, the modifications to the genetic architecture underpinning adaptive immunity or the fusion mating strategy? One of the species he examined may offer a clue. Gigantactis vanhoeffeni is thought to mate through temporary attachment, yet it shows some of the same alterations to immune genes as permanently attaching species. Boehm says he thinks G. vanhoeffeni could possibly be “en route to permanent attachment” evolutionarily. “It seems that some changes to the immune genome have to occur before this permanent fusion can really set in. It seems that there is some as yet unknown evolutionary pressure of some sort that [first] causes these genes to go extinct or defunct.”
Gil Rosenthal, an evolutionary biologist at Texas A&M University, says he wonders what those evolutionary pressures could be. Deep-sea anglerfish are extremely sexually dimorphic, he notes in an email to The Scientist. “Females are these nightmarish light-bearing fanged monsters, and males are tiny little things with a huge testis and a huge nose.” The females are probably sparse in the deep sea, so it’s likely that the males spend a lot of time looking for them, he explains. When a male finally finds a female, it would be in its interest to stick close. If it happens that the female has conflicting interests—such as eating the males—it could set up the fish for “sexual conflict.” That situation could somehow lead to a genomic tug-of-war over the immune system, Rosenthal speculates. “I wouldn’t be surprised if some of the wreckage of the immune genome comes from sexual conflict.”
It wouldn’t be the first example of a trade-off between sexual behavior and immune system function, he adds, noting that in vertebrates, testosterone can depress immune system function and enhance male sexual displays. However, “that so much of it is shut down or remodeled in [deep-sea anglerfish] is just wild!”
To Rosenthal and Murchison, the results underscore how the genomics revolution has enabled researchers to venture beyond well-understood model organisms in labs and explore the different adaptations of life on Earth. “There’s so much to be learned about not just immunity, but all of biology, by exploring evolutionarily divergent lineages,” Murchison says. “And you never really know what you’re going to find because nature is so broad and diverse and there’s so much adaptation to very specialized niches.”
J.B. Swann, et al. “The immunogenetics of sexual parasitism,” Science, doi:10.1126/science.aaz9445, 2020.


thescientist--2020-07-30--A Ticking Time Bomb: Tracing the Origin and Spread of SARS-CoV-2

For years , virologists predicted that coronaviruses would jump from animals to humans , causing new diseases .
Unfortunately , @ @ @ @ @ and SARS-CoV-2 now spreads across the globe .
Due to the COVID-19 pandemic , research @ @ @ @ @ of coronaviruses is taking center stage .
In this webinar from The Scientist , coronavirus @ @ @ @ @ came to infect humans .
Linda Saif will give a historical overview of SARS spillovers @ @ @ @ @ and Neville Sanjana will describe recent work on a SARS-CoV-2 spike protein variant that increases @ @ @ @ @ historical overview of coronavirus spillovers from animals to humans Linda J. Saif , PhD Distinguished @ @ @ @ @ Research Program and the College of Veterinary Medicine Co-Director Virus and Emerging Pathogens Program , @ @ @ @ @ State University Neville Sanjana , PhD Core Faculty Member , New York Genome Center Assistant @ @ @ @ @ York University Assistant Professor of Neuroscience and Physiology , NYU School of Medicine

FREE Webinar
Friday, August 14, 2020
11:00 AM - 12:30 PM, Eastern Standard Time
Register Now
For years, virologists predicted that coronaviruses would jump from animals to humans, causing new diseases. Unfortunately, those fears have been realized and SARS-CoV-2 now spreads across the globe. Due to the COVID-19 pandemic, research on the origins and spread of coronaviruses is taking center stage. In this webinar from The Scientist, coronavirus experts will describe how SARS-CoV-2 came to infect humans. Linda Saif will give a historical overview of SARS spillovers from animals to humans, and Neville Sanjana will describe recent work on a SARS-CoV-2 spike protein variant that increases human infectivity.
Topics to be covered
A historical overview of coronavirus spillovers from animals to humans
The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types
Register Now
Meet the speakers:
Linda J. Saif, PhD
Distinguished University Professor
Food Animal Health...


thescientist--2020-07-30--Initiative Seeks to CT Scan Kenya's Unexplored Fossil Trove

ABOVE : Various crocodile fossils in the paleontology collection at the Nairobi National Museum COURTESY OF JOB KIBII AND THE NATIONAL MUSEUMS OF KENYA The paleontology collection at the Nairobi National Museum is so vast that the bones of an extinct lion-like carnivore larger than a polar bear went unnoticed for three decades .
And they ’ re so old , there ’ s a chance whenever curator Job Kibii opens a drawer that the creature inside may be the earliest known of its kind .
The museum ’ s fossils , the majority of which span a time period @ @ @ @ @ @ @ million years ago , are sometimes encased in rock , which pristinely preserves details but obscures parts of specimens .
To look beneath the surface without destroying a sample , scientists typically look to high-resolution X-ray microtomography ( micro-CT ) scans , which allow them to build 3-D reconstructions of fossils at a microscopic scale .
Numerous micro-CT scanners exist in the Western world , resulting in more access than ever before to virtual reconstructions of fossils .
But there remain holes in availability of the instruments in other parts of the world @ @ @ @ @ @ @ share their scans online .
In Africa , only two micro-CT scanners—both in South Africa—are housed at academic research institutions , says Kibii .
The lack of instruments is a disparity hindering African paleontologists and isolating African fossils from researchers worldwide , adds Kibii , a senior research scientist and the head of paleontology and paleoanthropology for the National Museums of Kenya ( NMK ) , which includes the Nairobi museum .
“ Ninety-nine percent of the work we do here is just the surface , ” Kibii says .
But he intends @ @ @ @ @ @ @ study scanned data at NMK .
“ We should have the capacity to train our own people , ” he says .
Kibii is spearheading an NMK initiative to micro-CT scan Kenya ’ s fossils on a large scale for the first time .
It began in December 2015 , when Kibii partnered with the University of the Witwatersrand in South Africa , which houses one of the continent ’ s micro-CT machines , to scan a number of the museum ’ s fossils for free each year , rather than buy an @ @ @ @ @ @ @ have the resources to operate and maintain .
Micro-CT scanners can cost up to $ 1 million .
When it comes to micro-CT , African institutions accomplish more when they work together and join resources , according to one recent study .
The project ’ s goals include raising funds for a big data-storage and processing lab located in Nairobi at the National Museum , where 3-D images of the fossils will be reconstructed and shared internationally .
In addition to opening up new areas of research to Kenyans , scans preserve fossils @ @ @ @ @ @ @ can not .
When a fire ripped through Rio de Janeiro ’ s National Museum in 2018 , for example , the scientific community was devastated as hundreds of undigitized holotypes went up in smoke .
“ This is a new phase of doing research in Kenya , ” says Kibii .
“ The fossils are readily available .
The next step is to look at the insides of all those fossils and let ’ s see what they can tell us about the past .
The whole evolutionary story will be more @ @ @ @ @ @ @ different fossils.
” Since 2017 , Kibii has made two trips annually to South Africa with fossils in tow .
He ’ s carried fossil monkeys , carnivores , and even early hominids .
Each trip , he says , is as nerve wracking as the last .
“ You ’ re carrying original specimens for which you know there is no replacement if anything happens , ” says Kibii , who has to secure a government permit for each trip .
“ You panic a bit.
” Decades of losses due to @ @ @ @ @ @ @ strict laws that prevent these specimens from leaving the country unless accompanied by a Kenyan paleontologist , says Kibii .
Because there are only a handful of paleontologists in Kenya , he says , micro-CT scanning rarely happened before he began carrying them in batches to South Africa .
The paleontology collection in Nairobi began when famed 20th century paleontologists Louis and Mary Leakey first stored fossils there in the 1930s .
Since then , the collection has grown exponentially to become one of the best fossil troves in the world , documenting @ @ @ @ @ @ @ a region called the Cradle of Humanity because of the many early human ancestors discovered there , including Australopithecus anamensis and the 40-percent-complete skeleton of a Homo erectus child called Turkana Boy .
Casts of both specimens are on display in Nairobi , while the originals are stored in the hominid vault that Kibii curates .
The first indigenous African to earn a PhD from the Witwatersrand , Kibii was on the team that discovered Australopithecus sediba in 2008 in South Africa and has also found hominid specimens belonging to A. africanus .
@ @ @ @ @ @ @ in 2015 , he did so with the goal of bringing NMK ’ s historic paleontology collections into the 21st century .
“ I saw it as a good chance for me to come back to Kenya and implement some of the things I had learned in South Africa , ” he says .
Kibii ’ s project will provide cutting-edge data , moving paleontology forward in Kenya in the hands of Kenyan scientists , says paleontologist Ashley Hammond , an assistant curator of biological anthropology at the American Museum of Natural History @ @ @ @ @ @ @ NMK on hominoid fossils .
In the past , foreign researchers have gone so far as to bring their own scanners into Kenya , she says , but data held by outsiders aren ’ t always shared with NMK because the museums lacks the infrastructure to handle big data .
Kibii ’ s project will make it easier for researchers like herself to share their own data with NMK scientists and better utilize Kenyan expertise , Hammond says .
The project will also facilitate research opportunities and collaboration for scientists who would find @ @ @ @ @ @ @ paleontologist Sanaa El-Sayed , the cofounder and vice director of Mansoura University Vertebrate Paleontology Center in Egypt , writes in an email to The Scientist .
But keenly aware of the financial challenges facing African paleontology institutions , El-Sayed says the financial costs involved with NMK ’ s initiative could be a challenge for the institution , and she emphasizes that the museum will need to secure funding and training for staff to sustain it .
Kibii has reduced costs by partnering with Witwatersrand , which allows him to move forward with scanning @ @ @ @ @ @ @ for the cost of a plane ticket .
Eventually , outside researchers will be able to submit requests to Kibii ’ s team to have museum fossils scanned in South Africa for a reasonable fee .
To create a repository lab in Nairobi where micro-CT scans done in South Africa can be reconstructed into 3-D renderings and stored , paleontologist Thomas Lehmann , head of the paleomammalogy section at Senckenberg Research Institute in Germany , is preparing to apply for European grants this year to raise funds for the lab and to hire @ @ @ @ @ @ @ its operation in Kenya .
Lehman estimates the lab will cost around $ 100,000 to start up , but he ’ s confident the quality of the paleontology collection and the potential for new discoveries will draw funding .
“ If you look at Africa as a whole , there are not that many fossil collections that are as well kept as those in Kenya , except for South Africa , ” says Lehmann , who has been studying the museum ’ s paleontology collection since 2003 .
Prior to Kibii ’ s @ @ @ @ @ @ @ Lehmann had lots of ideas for studies involving the fossils there and questions about evolution and ecology , but he couldn ’ t answer them without micro-CT scans to look inside the fossils .
“ All these questions were there written down on a piece of paper .
It was getting longer and longer , ” he says .
“ Then here was Job opening the door.
” The initiative has already led to the discovery of new species , including an 18 million-year-old chameleon that may be the oldest ever found in @ @ @ @ @ @ @ years has permitted replicas of the skulls and bones of animals that were previously inaccessible and masked by matrix to be 3-D printed at the museum in Nairobi .
This new access to scans and 3-D fossil models will make paleontology more attractive to Kenyan students and could help the museum expand its outreach , Kibii says .
In April , Kibii planned to scan more fossils in South Africa , but the trip was canceled due to the COVID-19 pandemic .
He plans to scan a new assortment in December if conditions @ @ @ @ @ @ @ to examining more early human ancestors—his specialty .
“ COVID-19 has really changed the look of things , ” making micro-CT scanning even more imperative , he says .
If his vision were already fully realized , his team could send digital versions of fossils to researchers in Africa and abroad who are quarantined and face travel restrictions .
In that future world , he says , research will continue unhindered .

The museum’s fossils, the majority of which span a time period from recent times to more than 25 million years ago, are sometimes encased in rock, which pristinely preserves details but obscures parts of specimens. To look beneath the surface without destroying a sample, scientists typically look to high-resolution X-ray microtomography (micro-CT) scans, which allow them to build 3-D reconstructions of fossils at a microscopic scale.
The paleontology collection at the Nairobi National Museum is so vast that the bones of an extinct lion-like carnivore larger than a polar bear went unnoticed for three decades. And they’re so old, there’s a chance whenever curator Job Kibii opens a drawer that the creature inside may be the earliest known of its kind.
ABOVE: Various crocodile fossils in the paleontology collection at the Nairobi National Museum COURTESY OF JOB KIBII AND THE NATIONAL MUSEUMS OF KENYA
“Ninety-nine percent of the work we do here is just the surface,” Kibii says. But he intends to train Kenyans to work with and study scanned data at NMK. “We should have the capacity to train our own people,” he says.
Decades of losses due to theft or damage of fossils resulted in strict laws that prevent these specimens from leaving the country unless accompanied by a Kenyan paleontologist.
Kibii is spearheading an NMK initiative to micro-CT scan Kenya’s fossils on a large scale for the first time. It began in December 2015, when Kibii partnered with the University of the Witwatersrand in South Africa, which houses one of the continent’s micro-CT machines, to scan a number of the museum’s fossils for free each year, rather than buy an instrument that the museum wouldn’t have the resources to operate and maintain. Micro-CT scanners can cost up to $1 million. When it comes to micro-CT, African institutions accomplish more when they work together and join resources, according to one recent study. The project’s goals include raising funds for a big data-storage and processing lab located in Nairobi at the National Museum, where 3-D images of the fossils will be reconstructed and shared internationally.
In addition to opening up new areas of research to Kenyans, scans preserve fossils permanently in a way that physical museums cannot. When a fire ripped through Rio de Janeiro’s National Museum in 2018, for example, the scientific community was devastated as hundreds of undigitized holotypes went up in smoke.
“This is a new phase of doing research in Kenya,” says Kibii. “The fossils are readily available. The next step is to look at the insides of all those fossils and let’s see what they can tell us about the past. The whole evolutionary story will be more complete as we get more scans of different fossils.”
Since 2017, Kibii has made two trips annually to South Africa with fossils in tow. He’s carried fossil monkeys, carnivores, and even early hominids. Each trip, he says, is as nerve wracking as the last.
“You’re carrying original specimens for which you know there is no replacement if anything happens,” says Kibii, who has to secure a government permit for each trip. “You panic a bit.”
Decades of losses due to theft or damage of fossils resulted in strict laws that prevent these specimens from leaving the country unless accompanied by a Kenyan paleontologist, says Kibii. Because there are only a handful of paleontologists in Kenya, he says, micro-CT scanning rarely happened before he began carrying them in batches to South Africa.
Job Kibii, head of the National Museums of Kenya’s paleontology department, uses a total station to measure distances during a dig site survey. Courtesy of Job Kibii and the National Museums of Kenya
The paleontology collection in Nairobi began when famed 20th century paleontologists Louis and Mary Leakey first stored fossils there in the 1930s. Since then, the collection has grown exponentially to become one of the best fossil troves in the world, documenting the evolutionary history of East Africa, a region called the Cradle of Humanity because of the many early human ancestors discovered there, including Australopithecus anamensis and the 40-percent-complete skeleton of a Homo erectus child called Turkana Boy. Casts of both specimens are on display in Nairobi, while the originals are stored in the hominid vault that Kibii curates.
The first indigenous African to earn a PhD from the Witwatersrand, Kibii was on the team that discovered Australopithecus sediba in 2008 in South Africa and has also found hominid specimens belonging to A. africanus. When he returned to his native Kenya in 2015, he did so with the goal of bringing NMK’s historic paleontology collections into the 21st century.
“I saw it as a good chance for me to come back to Kenya and implement some of the things I had learned in South Africa,” he says.
Kibii’s project will provide cutting-edge data, moving paleontology forward in Kenya in the hands of Kenyan scientists, says paleontologist Ashley Hammond, an assistant curator of biological anthropology at the American Museum of Natural History whose research involves working with researchers at NMK on hominoid fossils. In the past, foreign researchers have gone so far as to bring their own scanners into Kenya, she says, but data held by outsiders aren’t always shared with NMK because the museums lacks the infrastructure to handle big data. Kibii’s project will make it easier for researchers like herself to share their own data with NMK scientists and better utilize Kenyan expertise, Hammond says.
The project will also facilitate research opportunities and collaboration for scientists who would find it difficult to visit Kenya, vertebrate paleontologist Sanaa El-Sayed, the cofounder and vice director of Mansoura University Vertebrate Paleontology Center in Egypt, writes in an email to The Scientist. But keenly aware of the financial challenges facing African paleontology institutions, El-Sayed says the financial costs involved with NMK’s initiative could be a challenge for the institution, and she emphasizes that the museum will need to secure funding and training for staff to sustain it.
Kibii has reduced costs by partnering with Witwatersrand, which allows him to move forward with scanning a limited number of fossils in batches for the cost of a plane ticket. Eventually, outside researchers will be able to submit requests to Kibii’s team to have museum fossils scanned in South Africa for a reasonable fee.
To create a repository lab in Nairobi where micro-CT scans done in South Africa can be reconstructed into 3-D renderings and stored, paleontologist Thomas Lehmann, head of the paleomammalogy section at Senckenberg Research Institute in Germany, is preparing to apply for European grants this year to raise funds for the lab and to hire and train a Kenyan technician to manage its operation in Kenya. Lehman estimates the lab will cost around $100,000 to start up, but he’s confident the quality of the paleontology collection and the potential for new discoveries will draw funding.
The initiative has already led to the discovery of new species, including an 18 million-year-old chameleon that may be the oldest ever found in Africa.
“If you look at Africa as a whole, there are not that many fossil collections that are as well kept as those in Kenya, except for South Africa,” says Lehmann, who has been studying the museum’s paleontology collection since 2003.
Prior to Kibii’s arrival at the museum in 2015, Lehmann had lots of ideas for studies involving the fossils there and questions about evolution and ecology, but he couldn’t answer them without micro-CT scans to look inside the fossils. “All these questions were there written down on a piece of paper. It was getting longer and longer,” he says. “Then here was Job opening the door.”
The initiative has already led to the discovery of new species, including an 18 million-year-old chameleon that may be the oldest ever found in Africa. Scanning over the last few years has permitted replicas of the skulls and bones of animals that were previously inaccessible and masked by matrix to be 3-D printed at the museum in Nairobi. This new access to scans and 3-D fossil models will make paleontology more attractive to Kenyan students and could help the museum expand its outreach, Kibii says.
In April, Kibii planned to scan more fossils in South Africa, but the trip was canceled due to the COVID-19 pandemic. He plans to scan a new assortment in December if conditions allow, and says he looks forward to examining more early human ancestors—his specialty.
“COVID-19 has really changed the look of things,” making micro-CT scanning even more imperative, he says. If his vision were already fully realized, his team could send digital versions of fossils to researchers in Africa and abroad who are quarantined and face travel restrictions. In that future world, he says, research will continue unhindered.


thescientist--2020-07-29--Experimental Blood Test Could Flag Alzheimer's

Three studies presented at the Alzheimer ’ s Association International Conference this week describe the performance of blood tests used to diagnose , and even predict , Alzheimer ’ s disease using circulating levels of a form of tau protein called p-tau217 .
The largest assessment of this approach , which included 1,402 participants , showed that circulating p-tau217 levels worked just as well at detecting Alzheimer ’ s as standard PET scans and tests of cerebrospinal fluid .
“ This blood test very , very accurately predicts who ’ s got Alzheimer ’ s disease in their brain , @ @ @ @ @ @ @ , ” Michael Weiner , an Alzheimer ’ s disease researcher at the University of California , San Francisco , who was not involved in the study , tells The New York Times .
“ It ’ s not a cure , it ’ s not a treatment , but you can ’ t treat the disease without being able to diagnose it .
And accurate , low-cost diagnosis is really exciting , so it ’ s a breakthrough.
” A blood test could help identify people on track to develop Alzheimer ’ @ @ @ @ @ @ @ in drug trials aimed at finding an effective treatment for the disease .
Scientists have pursued a number of potential circulating biomarkers , such as amyloid-β , to find those that can reliably diagnose Alzheimer ’ s disease or predict its development , but to date none have come to market .
See “ The Hunt for a Blood Test for Alzheimer ’ s Disease ” High levels of tau or its phosphorylated form , p-tau , have emerged as promising biomarker candidates because they may indicate the presence of damaging structures known @ @ @ @ @ @ @ The large study on one type of p-tau , p-tau217 , published in JAMA July 28 to coincide with the presentation at the meeting , was a collection of three experiments using a blood test developed by Eli Lilly ( some of the coauthors work for the company ) .
In one assessment of several hundred Swedes , the test accurately distinguished patients who had Alzheimer ’ s from those with other forms of dementia with 89–98 percent accuracy .
“ That ’ s pretty good .
We ’ ve never seen that @ @ @ @ @ @ @ the Alzheimer ’ s Association ’ s chief science officer , tells the Associated Press .
In another assessment of the Eli Lilly test , which included hundreds of related individuals , some of whom have a gene that causes Alzheimer ’ s , p-tau217 levels in the blood aligned with the genetics , even decades before cognitive impairment is likely to begin .
Another study presented at the conference found a p-tau217 blood test could accurately distinguish Alzheimer ’ s patients from those with frontotemporal lobar degeneration , according to a conference @ @ @ @ @ @ @ of a study by Suzanne Schindler of Washington University in St. Louis and her colleagues reported that circulating p-tau217 was superior to another form that ’ s been studied as a potential biomarker , p-tau181 , as a proxy for amyloid accumulation in the brain .
“ I personally find it very reassuring that these different groups are using different types of assays and getting the same result , ” Schindler tells the Times .
“ It looks real .
It looks like 217 has tremendous promise as a blood test for Alzheimer @ @ @ @ @ @ @ likely to correspond with the symptoms.
” Speaking to The Guardian , Clive Ballard , who studies age-related disease at the University of Exeter Medical School and who was not involved in these projects , says , “ further validation in people from more routine clinical settings are still needed , and a lot of work will be needed to achieve standardisation of the test across laboratories—so it could still be at least five years before we see an accurate blood biomarker test for dementia in the clinic .
”

“This blood test very, very accurately predicts who’s got Alzheimer’s disease in their brain, including people who seem to be normal,” Michael Weiner, an Alzheimer’s disease researcher at the University of California, San Francisco, who was not involved in the study, tells The New York Times . “It’s not a cure, it’s not a treatment, but you can’t treat the disease without being able to diagnose it. And accurate, low-cost diagnosis is really exciting, so it’s a breakthrough.”...
Three studies presented at the Alzheimer’s Association International Conference this week describe the performance of blood tests used to diagnose, and even predict, Alzheimer’s disease using circulating levels of a form of tau protein called p-tau217. The largest assessment of this approach, which included 1,402 participants, showed that circulating p-tau217 levels worked just as well at detecting Alzheimer’s as standard PET scans and tests of cerebrospinal fluid.
A blood test could help identify people on track to develop Alzheimer’s early on—and perhaps get them enrolled in drug trials aimed at finding an effective treatment for the disease. Scientists have pursued a number of potential circulating biomarkers, such as amyloid-β, to find those that can reliably diagnose Alzheimer’s disease or predict its development, but to date none have come to market.
High levels of tau or its phosphorylated form, p-tau, have emerged as promising biomarker candidates because they may indicate the presence of damaging structures known as neurofibrillary tangles in the brain.
The large study on one type of p-tau, p-tau217, published in JAMA July 28 to coincide with the presentation at the meeting, was a collection of three experiments using a blood test developed by Eli Lilly (some of the coauthors work for the company). In one assessment of several hundred Swedes, the test accurately distinguished patients who had Alzheimer’s from those with other forms of dementia with 89–98 percent accuracy. “That’s pretty good. We’ve never seen that” precision before, Maria Carrillo, the Alzheimer’s Association’s chief science officer, tells the Associated Press.
In another assessment of the Eli Lilly test, which included hundreds of related individuals, some of whom have a gene that causes Alzheimer’s, p-tau217 levels in the blood aligned with the genetics, even decades before cognitive impairment is likely to begin.
Another study presented at the conference found a p-tau217 blood test could accurately distinguish Alzheimer’s patients from those with frontotemporal lobar degeneration, according to a conference press release. And a third presentation of a study by Suzanne Schindler of Washington University in St. Louis and her colleagues reported that circulating p-tau217 was superior to another form that’s been studied as a potential biomarker, p-tau181, as a proxy for amyloid accumulation in the brain.
“I personally find it very reassuring that these different groups are using different types of assays and getting the same result,” Schindler tells the Times. “It looks real. It looks like 217 has tremendous promise as a blood test for Alzheimer’s disease, and it is likely to correspond with the symptoms.”
Speaking to The Guardian, Clive Ballard, who studies age-related disease at the University of Exeter Medical School and who was not involved in these projects, says, “further validation in people from more routine clinical settings are still needed, and a lot of work will be needed to achieve standardisation of the test across laboratories—so it could still be at least five years before we see an accurate blood biomarker test for dementia in the clinic.”