thescientist--2020-09-09--COVID-19 Vaccine Trial Pauses After Adverse Reaction

A series of late-stage clinical trials establishing the effectiveness and safety of a joint AstraZeneca and University of Oxford COVID-19 vaccine are on hold after one UK participant in a Phase 3 trial developed a severe and unexplained illness .
The incident was first reported on Tuesday ( September 8 ) by STAT .
The pause will delay results from one of the world ’ s largest COVID-19 vaccine development efforts .
A company spokesperson says the measure has been taken out of an abundance of caution .
“ This is a routine action which has to happen whenever there @ @ @ @ @ @ @ of the trials , while it is investigated , ” AstraZeneca shared in a prepared statement .
“ We are working to expedite the review of the single event to minimize any potential impact on the trial timeline .
We are committed to the safety of our participants and the highest standards of conduct in our trials.
” Details of the adverse event that initiated the pause , including how serious it is and when it happened , have not been shared publicly .
A person familiar with the situation , speaking on @ @ @ @ @ @ @ Times says that the participant had been diagnosed with transverse myelitis , an inflammatory condition in the spinal cord that is often sparked by viral infections .
Gabriella Garcia , a neurologist at Yale New Haven Hospital , tells the Times transverse myelitis is often treatable with steroids .
When asked to confirm the diagnosis , AstraZeneca declined to comment .
“ The event is being investigated by an independent committee , and it is too early to conclude the specific diagnosis , ” the company says .
Currently , there are nine @ @ @ @ @ @ @ and AstraZeneca is the first to announce a pause .
It is unknown how long the hold will continue .
Marie-Paule Kieny , a vaccine researcher at INSERM , the national health research institute in Paris , tells Nature that if AstraZeneca can quickly rule out the vaccine as a source of the illness , the trial could be running again “ in a matter of weeks.
” One Phase 3 trial has been underway in the US since late August with plans to enroll up to 30,000 participants at 80 sites across @ @ @ @ @ @ @ same vaccine are also progressing in other countries , including Brazil and South Africa , with additional trials planned for Japan and Russia .
Money to fund the US trial came from Operation Warp Speed , a US federal initiative to quickly disperse funds to the most promising vaccine candidates .
AstraZeneca received $ 1.2 billion dollars to produce 300 million doses , Buzzfeed reports .
The company ’ s vaccine relies on an experimental method , based on an adenovirus vector from chimpanzees , that has yet to lead to any approved @ @ @ @ @ @ @ in studies to treat influenza and Ebola , according to STAT .
Scientists engineered the virus to smuggle the gene for the SARS-CoV-2 spike protein into human cells .
Once inside , the protein prompts a natural immune response , priming immune cells to recognize SARS-CoV-2 .
See “ Vector-Based Vaccines Come to the Fore in the COVID-19 Pandemic ” The Phase 1 and 2 trials of the vaccine involved 1,077 patients , Buzzfeed reports , and the results showed that 90 percent of participants subsequently tested positive for neutralizing antibodies .
While @ @ @ @ @ @ @ or moderate side effects such as fever , headaches , and muscle aches , these symptoms resolved before the end of the trial .
Phase 3 trials , which assess efficacy , can also look for less common side effects only be detected when vaccines are tested on large numbers of people .
Because of their large size , these studies are considered the most important for establishing safety , according to the Associated Press .
Some scientists are saying the pause is not unexpected , and in fact shows that the clinical @ @ @ @ @ @ @ .
On the same day that AstraZeneca announced the suspension , the company ’ s CEO joined eight other pharmaceutical companies in announcing a commitment to integrity and safety moving forward with vaccine trials .
“ This is the whole point of doing these Phase 2 , Phase 3 trials , ” Phyllis Tien , an infectious disease physician at the University of California , San Francisco , tells the Times .
“ We need to assess safety , and we won ’ t know the efficacy part until much later .
I @ @ @ @ @ @ @ board can figure out whether or not this was directly related to the vaccine is a good idea.
” Pauses in trials can happen for any number of reasons .
Any unexplained illness that requires hospitalization , for example , could trigger a safety assessment to determine if it is linked to an injection with an experimental vaccine .
“ It does happen .
It ’ s not common , but it does happen , ” Paul Offit , a vaccine expert at Children ’ s Hospital of Philadelphia , tells BuzzFeed .
@ @ @ @ @ @ @ .
It ’ s not designed to stop everything else that happens in life .
You want to make sure it was related to the vaccine , especially if it happened a short period of time after the vaccine begins.
” Joe Walters , one of the participants in the University of Oxford trial in the UK , spoke this week to The Guardian about his experiences , sharing that he developed a persistent fever after receiving his initial injection ( although it ’ s unknown whether he received the vaccine candidate or @ @ @ @ @ @ @ hospitalized and tested for COVID-19 , and after his test came back negative , he learned that other participants had experienced similar side effects .
Walters heard about the pause the day he came to receive his second dose .
For now , his participation is on hold , but Walters says he plans to continue “ in the name of science , ” adding that the trial is “ something positive to do in the face of something that rendered everyone rather helpless.
” AstraZeneca is one of three companies testing vaccines @ @ @ @ @ @ @ .
The other two companies , Moderna and BioNTech , are developing vaccines using different methods than those used by AstraZeneca .
A spokesperson for Moderna tells the Times the firm ’ s work has not been affected by the latest pause .

ABOVE: © ISTOCK.COM, ZORANM
Update (September 14): Oxford University and AstraZeneca announced Saturday, September 12, that they will be resuming their UK trials after a temporary pause following a case of transverse myelitis in a UK patient.
A series of late-stage clinical trials establishing the effectiveness and safety of a joint AstraZeneca and University of Oxford COVID-19 vaccine are on hold after one UK participant in a Phase 3 trial developed a severe and unexplained illness.
The incident was first reported on Tuesday (September 8) by STAT. The pause will delay results from one of the world’s largest COVID-19 vaccine development efforts. A company spokesperson says the measure has been taken out of an abundance of caution.
“This is a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials, while it is investigated,” AstraZeneca shared in a prepared statement. “We are working to expedite the review of the single event to minimize any potential impact on the trial timeline. We are committed to the safety of our participants and the highest standards of conduct in our trials.”
Details of the adverse event that initiated the pause, including how serious it is and when it happened, have not been shared publicly. A person familiar with the situation, speaking on condition of anonymity with The New York Times , says that the participant had been diagnosed with transverse myelitis, an inflammatory condition in the spinal cord that is often sparked by viral infections.
Gabriella Garcia, a neurologist at Yale New Haven Hospital, tells the Times transverse myelitis is often treatable with steroids. When asked to confirm the diagnosis, AstraZeneca declined to comment. “The event is being investigated by an independent committee, and it is too early to conclude the specific diagnosis,” the company says.
Currently, there are nine vaccine candidates in Phase 3 trials, and AstraZeneca is the first to announce a pause. It is unknown how long the hold will continue. Marie-Paule Kieny, a vaccine researcher at INSERM, the national health research institute in Paris, tells Nature that if AstraZeneca can quickly rule out the vaccine as a source of the illness, the trial could be running again “in a matter of weeks.”
One Phase 3 trial has been underway in the US since late August with plans to enroll up to 30,000 participants at 80 sites across the country. Other trials of the same vaccine are also progressing in other countries, including Brazil and South Africa, with additional trials planned for Japan and Russia. Money to fund the US trial came from Operation Warp Speed, a US federal initiative to quickly disperse funds to the most promising vaccine candidates. AstraZeneca received $1.2 billion dollars to produce 300 million doses, Buzzfeed reports.
The company’s vaccine relies on an experimental method, based on an adenovirus vector from chimpanzees, that has yet to lead to any approved immunizations, although it was used previously in studies to treat influenza and Ebola, according to STAT. Scientists engineered the virus to smuggle the gene for the SARS-CoV-2 spike protein into human cells. Once inside, the protein prompts a natural immune response, priming immune cells to recognize SARS-CoV-2.
The Phase 1 and 2 trials of the vaccine involved 1,077 patients, Buzzfeed reports, and the results showed that 90 percent of participants subsequently tested positive for neutralizing antibodies. While roughly 60 percent of patients reported mild or moderate side effects such as fever, headaches, and muscle aches, these symptoms resolved before the end of the trial.
Phase 3 trials, which assess efficacy, can also look for less common side effects only be detected when vaccines are tested on large numbers of people. Because of their large size, these studies are considered the most important for establishing safety, according to the Associated Press.
Some scientists are saying the pause is not unexpected, and in fact shows that the clinical trial protocol is operating as it should. On the same day that AstraZeneca announced the suspension, the company’s CEO joined eight other pharmaceutical companies in announcing a commitment to integrity and safety moving forward with vaccine trials.
“This is the whole point of doing these Phase 2, Phase 3 trials,” Phyllis Tien, an infectious disease physician at the University of California, San Francisco, tells the Times. “We need to assess safety, and we won’t know the efficacy part until much later. I think halting the trial until the safety board can figure out whether or not this was directly related to the vaccine is a good idea.”
Pauses in trials can happen for any number of reasons. Any unexplained illness that requires hospitalization, for example, could trigger a safety assessment to determine if it is linked to an injection with an experimental vaccine. “It does happen. It’s not common, but it does happen,” Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia, tells BuzzFeed. “The vaccine is to stop SARS-CoV-2. It’s not designed to stop everything else that happens in life. You want to make sure it was related to the vaccine, especially if it happened a short period of time after the vaccine begins.”
Joe Walters, one of the participants in the University of Oxford trial in the UK, spoke this week to The Guardian about his experiences, sharing that he developed a persistent fever after receiving his initial injection (although it’s unknown whether he received the vaccine candidate or a control). He was briefly hospitalized and tested for COVID-19, and after his test came back negative, he learned that other participants had experienced similar side effects.
Walters heard about the pause the day he came to receive his second dose. For now, his participation is on hold, but Walters says he plans to continue “in the name of science,” adding that the trial is “something positive to do in the face of something that rendered everyone rather helpless.”
AstraZeneca is one of three companies testing vaccines in late-stage clinical trials in the US. The other two companies, Moderna and BioNTech, are developing vaccines using different methods than those used by AstraZeneca. A spokesperson for Moderna tells the Times the firm’s work has not been affected by the latest pause.


thescientist--2020-09-10--New Map Charts Genetic Expression Across Tissue Types, Sexes

A new , comprehensive catalog of differences in gene expression across dozens of human tissue types reveals previously unknown connections between genes and their regulatory DNA , researchers report today ( September 10 ) .
The work , unveiled in a series of papers published in Science , Science Advances , Cell , and other journals , details the third and final part of the Genotype-Tissue Expression ( GTEx ) project , which launched more than a decade ago to explore population-specific and sex-specific differences in gene expression to glean insight into how those differences may play a role in @ @ @ @ @ @ @ of the project , the researchers collected samples of multiple tissue types from more than 900 deceased human donors .
The team then sequenced the donors ’ genomes and measured gene activity by quantifying RNA levels in the tissues .
Having multiple tissues from the same person , as well as a variety of donors , the GTEx team could use statistical analyses to link DNA variants to gene expression differences and map gene regulation in up to 54 different types of tissues .
The work created an invaluable resource for analyzing gene @ @ @ @ @ @ @ or cell types , Jan Korbel , a human geneticist at the European Molecular Biology Laboratory ( EMBL ) in Heidelberg , Germany , tells Science .
From the data , the GTEx team could identify the relationship between specific genes and a type of regulatory DNA called expression quantitative trait loci , or eQTL .
At least one eQTL regulates almost every human gene , and each eQTL can regulate more than one gene , influencing expression , GTEx member and human geneticist Kristin Ardlie of the Broad Institute tells Science .
@ @ @ @ @ @ @ that sex affected gene expression in almost all of the tissue types , from heart to lung to brain cells .
“ The vast majority of biology is shared by males and females , ” yet the gene expression differences are vast and might explain differences in disease progression , GTEx study coauthor Barbara Stranger of Northwestern University ’ s Feinberg School of Medicine tells Science .
“ In the future , this knowledge may contribute to personalized medicine , where we consider biological sex as one of the relevant components of an @ @ @ @ @ @ @ says in a statement issued by the Centre for Genome Regulation in Barcelona , where some of the researchers who participated in the GTEx project work .
Another of the studies bolsters the association between telomere length , ancestry , and aging .
Telomere length is typically measured in blood cells ; GTEx researchers examined it in 23 different tissue types and found blood is indeed a good proxy for overall length in other tissues .
The team also showed that , as previously reported , shorter telomeres were associated with aging and @ @ @ @ @ @ @ African ancestry .
But not all earlier results held ; the authors didn ’ t see a pattern of longer telomeres in females or constantly shorter telomeres across the tissues of smokers as previous studies had .
Not everyone is singing the project ’ s praises .
Dan Graur , an evolutionary biologist at the University of Houston who often criticizes big projects like GTEx , tells Science the results are hard to parse and there was little diversity , with 85 percent of the tissue donors being white .
He also was @ @ @ @ @ @ @ tissue , questioning if it truly reflects gene activity in living humans .
“ It ’ s like studying the mating behaviour of roadkill.
” Other scientists say there ’ s much work to be done .
The gene regulation map leaves many unanswered questions about the exact sequences that cause disease and how gene regulation systems work in tandem .
Genomicist Ewan Birney , the deputy director general of EMBL , tells Science , “ We shouldn ’ t pack up our bags and say gene expression is solved .
”

© ISTOCK.COM, MAGNILION
A new, comprehensive catalog of differences in gene expression across dozens of human tissue types reveals previously unknown connections between genes and their regulatory DNA, researchers report today (September 10).
The work, unveiled in a series of papers published in Science, Science Advances, Cell, and other journals, details the third and final part of the Genotype-Tissue Expression (GTEx) project, which launched more than a decade ago to explore population-specific and sex-specific differences in gene expression to glean insight into how those differences may play a role in aging and disease.
During the course of the project, the researchers collected samples of multiple tissue types from more than 900 deceased human donors. The team then sequenced the donors’ genomes and measured gene activity by quantifying RNA levels in the tissues. Having multiple tissues from the same person, as well as a variety of donors, the GTEx team could use statistical analyses to link DNA variants to gene expression differences and map gene regulation in up to 54 different types of tissues. The work created an invaluable resource for analyzing gene expression in particular diseases, tissues, or cell types, Jan Korbel, a human geneticist at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, tells Science.
From the data, the GTEx team could identify the relationship between specific genes and a type of regulatory DNA called expression quantitative trait loci, or eQTL. At least one eQTL regulates almost every human gene, and each eQTL can regulate more than one gene, influencing expression, GTEx member and human geneticist Kristin Ardlie of the Broad Institute tells Science.
In the project, 54 tissue types were examined, including 11 distinct brain regions. In the illustration, the sample numbers from genotyped donors are in parentheses. Aguet et al., Science 2020
Another major takeaway from the analyses was that sex affected gene expression in almost all of the tissue types, from heart to lung to brain cells. “The vast majority of biology is shared by males and females,” yet the gene expression differences are vast and might explain differences in disease progression, GTEx study coauthor Barbara Stranger of Northwestern University’s Feinberg School of Medicine tells Science. “In the future, this knowledge may contribute to personalized medicine, where we consider biological sex as one of the relevant components of an individual’s characteristics,” she says in a statement issued by the Centre for Genome Regulation in Barcelona, where some of the researchers who participated in the GTEx project work.
Another of the studies bolsters the association between telomere length, ancestry, and aging. Telomere length is typically measured in blood cells; GTEx researchers examined it in 23 different tissue types and found blood is indeed a good proxy for overall length in other tissues. The team also showed that, as previously reported, shorter telomeres were associated with aging and longer ones were found in people of African ancestry. But not all earlier results held; the authors didn’t see a pattern of longer telomeres in females or constantly shorter telomeres across the tissues of smokers as previous studies had.
Not everyone is singing the project’s praises. Dan Graur, an evolutionary biologist at the University of Houston who often criticizes big projects like GTEx, tells Science the results are hard to parse and there was little diversity, with 85 percent of the tissue donors being white. He also was critical of the use of deceased donor tissue, questioning if it truly reflects gene activity in living humans. “It’s like studying the mating behaviour of roadkill.”
Other scientists say there’s much work to be done. The gene regulation map leaves many unanswered questions about the exact sequences that cause disease and how gene regulation systems work in tandem. Genomicist Ewan Birney, the deputy director general of EMBL, tells Science, “We shouldn’t pack up our bags and say gene expression is solved.”


thescientist--2020-09-10--Bird Flu Viruses Can Remain Infectious for Months in US Wetlands

Avian influenza viruses can remain infectious in the surface water of northern US wetlands for at least seven months , according to a study published yesterday ( September 9 ) in Proceedings of the Royal Society B .
Using a combination of lab and field experiments , researchers at the United States Geological Survey ( USGS ) showed that viruses shed by wild ducks were still viable after more than 209 days in situ , suggesting that these areas could act as environmental reservoirs for the pathogens while birds overwinter in areas further south .
“ It ’ s saying @ @ @ @ @ @ @ get serious about the role the environment plays in the transmission of avian influenza , ” says Chelsea Himsworth , a veterinary pathologist at the University of British Columbia and the Canadian Wildlife Health Cooperative who was not involved in the work .
“ The environment tends to be neglected ” in disease studies , she says , but the new findings suggest “ maybe viruses are hiding out in these waters , maybe they ’ re surviving for long periods , they ’ re re-infecting birds between migration cycles.
” Avian influenza @ @ @ @ @ @ @ by influenza A viruses , which are common in wild birds and can cause economically damaging outbreaks in poultry when transmitted via droppings or contaminated water or surfaces .
Although avian influenza viruses typically pose no direct threat to humans , there have been occasional reports of infections in people who work with domesticated birds and , very rarely , person-to-person transmission , making surveillance of the viruses an important public health focus .
Previous work by various research groups had already shown that avian influenza viruses could remain infectious in water for @ @ @ @ @ @ @ USGS research scientist Andy Ramey .
But these studies typically use “ really controlled settings , ” he says .
While such research is important for learning about the effects of temperature , pH , and other water conditions on virus viability , “ it ’ s not really realistic of any ponds or lakes that I ’ m familiar with.
” To get a better idea of the viruses ’ persistence in the field , Ramey and colleagues collected and filtered water from wetlands in Alaska and Minnesota in late 2018 , @ @ @ @ @ @ @ taken from ducks .
They then took half of the samples to the lab to be maintained in constant conditions and put the other half into perforated steel drums that they left submerged in the wetland sites the samples had come from .
Initial genetic analyses of the lab-kept samples revealed several avian influenza strains such as H3N8 and H4N6 .
By testing those samples every month over the winter of 2018–2019 , the team found that although the amount of viable influenza virus declined over time , about 13 percent of the @ @ @ @ @ @ @ beginning of the experiment still yielded viable virus around seven months later .
Analyses of the wetland-stored samples in spring 2019 produced similar findings : around one-fifth of the samples that had contained viable virus at the beginning of the experiment still contained viable virus after 209–229 days stored in situ .
Genetic sequencing confirmed that the viruses at the end of the experiment were the same ones detected at the beginning—not the result of environmental contamination , Ramey says .
In an additional experiment , the researchers confirmed that the influenza viruses @ @ @ @ @ @ @ still infectious by inoculating live mallards .
Of nine samples the team used to inoculate different ducks , at least two—one sample from Minnesota and one from Alaska—caused infections in the birds , they report in their paper .
Ursula Höfle , a veterinary scientist at the University of Castilla-La Mancha in Spain , says the work is “ one of the studies we really needed.
” She notes that researchers studying avian influenza often detect almost genetically identical viruses in populations of ducks from season to season—an unexpected finding given the fast @ @ @ @ @ @ @ hosts .
If infectious virus can stick around in the environment when bird populations aren ’ t there , that could explain this observation , she says .
Björn Olsen , an infectious diseases researcher and physician at Uppsala University in Sweden , calls the study a “ very valuable contribution to understanding how this virus circulates in the environment.
” Olsen , who has previously collaborated with Ramey but was not involved in the current study , notes that the findings could have implications for wetland management .
“ It ’ s @ @ @ @ @ @ @ new wetlands in green areas all over the world , ” he says .
“ I think it ’ s important to realize there can be some negative effects [ of this ] as well.
” While the findings provide a proof of concept that viable virus can persist in the environment , researchers who spoke to The Scientist caution that more work is needed to confirm how significant this phenomenon is as a cause of bird infections .
Höfle points out , for example , that filtering water samples removes bacteria , @ @ @ @ @ @ @ aquatic systems that may affect virus infectivity over time .
It also remains to be seen how broadly the findings apply beyond northern US states , says Ramey .
The team collected additional samples from Louisiana in the study , but initial tests after those lab samples had been inoculated with duck swabs didn ’ t detect any viable virus—perhaps because of the temperature or pH conditions of the water itself—although some tested positive for viral RNA .
The Minnesota and Alaska data hinted at potential differences between those states ’ wetlands , @ @ @ @ @ @ @ more frequently in Minnesotan samples than in Alaskan ones .
This kind of variation in virus infectivity with geography and specific environment will be an important avenue to explore in the future , says Himsworth , particularly for researchers who want to understand how future environmental changes may affect disease transmission or for studies that attempt to use environmental samples as part of virus surveillance .
“ I think the variability they even found within the study points to the fact that all of us , in our jurisdictions , need to get @ @ @ @ @ @ @ A.M. Ramey et al.
, “ Influenza A viruses remain infectious for more than seven months in northern wetlands of North America , ” Proc R Soc B , 20201680 , 2020 .

ABOVE: Technician Lindsay Carlson swabs a hunter-harvested duck in western Alaska.
ANDREW REEVES, USGS
Avian influenza viruses can remain infectious in the surface water of northern US wetlands for at least seven months, according to a study published yesterday (September 9) in Proceedings of the Royal Society B. Using a combination of lab and field experiments, researchers at the United States Geological Survey (USGS) showed that viruses shed by wild ducks were still viable after more than 209 days in situ, suggesting that these areas could act as environmental reservoirs for the pathogens while birds overwinter in areas further south.
“It’s saying to the scientific community we need to get serious about the role the environment plays in the transmission of avian influenza,” says Chelsea Himsworth, a veterinary pathologist at the University of British Columbia and the Canadian Wildlife Health Cooperative who was not involved in the work. “The environment tends to be neglected” in disease studies, she says, but the new findings suggest “maybe viruses are hiding out in these waters, maybe they’re surviving for long periods, they’re re-infecting birds between migration cycles.”
Avian influenza, or bird flu, is caused by influenza A viruses, which are common in wild birds and can cause economically damaging outbreaks in poultry when transmitted via droppings or contaminated water or surfaces. Although avian influenza viruses typically pose no direct threat to humans, there have been occasional reports of infections in people who work with domesticated birds and, very rarely, person-to-person transmission, making surveillance of the viruses an important public health focus.
Previous work by various research groups had already shown that avian influenza viruses could remain infectious in water for long periods in the lab, notes USGS research scientist Andy Ramey. But these studies typically use “really controlled settings,” he says. While such research is important for learning about the effects of temperature, pH, and other water conditions on virus viability, “it’s not really realistic of any ponds or lakes that I’m familiar with.”
USGS scientist Andrew Reeves retrieves samples in Alaska. ANDREW RAMEY, USGS
To get a better idea of the viruses’ persistence in the field, Ramey and colleagues collected and filtered water from wetlands in Alaska and Minnesota in late 2018, and inoculated those water samples with swabs taken from ducks. They then took half of the samples to the lab to be maintained in constant conditions and put the other half into perforated steel drums that they left submerged in the wetland sites the samples had come from.
Initial genetic analyses of the lab-kept samples revealed several avian influenza strains such as H3N8 and H4N6. By testing those samples every month over the winter of 2018–2019, the team found that although the amount of viable influenza virus declined over time, about 13 percent of the samples that had tested positive at the beginning of the experiment still yielded viable virus around seven months later.
Analyses of the wetland-stored samples in spring 2019 produced similar findings: around one-fifth of the samples that had contained viable virus at the beginning of the experiment still contained viable virus after 209–229 days stored in situ. Genetic sequencing confirmed that the viruses at the end of the experiment were the same ones detected at the beginning—not the result of environmental contamination, Ramey says.
In an additional experiment, the researchers confirmed that the influenza viruses contained in the wetland-stored samples really were still infectious by inoculating live mallards. Of nine samples the team used to inoculate different ducks, at least two—one sample from Minnesota and one from Alaska—caused infections in the birds, they report in their paper.
Ursula Höfle, a veterinary scientist at the University of Castilla-La Mancha in Spain, says the work is “one of the studies we really needed.” She notes that researchers studying avian influenza often detect almost genetically identical viruses in populations of ducks from season to season—an unexpected finding given the fast rate at which these viruses evolve within hosts. If infectious virus can stick around in the environment when bird populations aren’t there, that could explain this observation, she says.
It’s saying to the scientific community we need to get serious about the role the environment plays in the transmission of avian influenza. —Chelsea Himsworth,
University of British Columbia and Canadian Wildlife Health Cooperative
Björn Olsen, an infectious diseases researcher and physician at Uppsala University in Sweden, calls the study a “very valuable contribution to understanding how this virus circulates in the environment.” Olsen, who has previously collaborated with Ramey but was not involved in the current study, notes that the findings could have implications for wetland management. “It’s more and more popular now to build new wetlands in green areas all over the world,” he says. “I think it’s important to realize there can be some negative effects [of this] as well.”
While the findings provide a proof of concept that viable virus can persist in the environment, researchers who spoke to The Scientist caution that more work is needed to confirm how significant this phenomenon is as a cause of bird infections. Höfle points out, for example, that filtering water samples removes bacteria, algae, and other components of real-life aquatic systems that may affect virus infectivity over time.
It also remains to be seen how broadly the findings apply beyond northern US states, says Ramey. The team collected additional samples from Louisiana in the study, but initial tests after those lab samples had been inoculated with duck swabs didn’t detect any viable virus—perhaps because of the temperature or pH conditions of the water itself—although some tested positive for viral RNA. The Minnesota and Alaska data hinted at potential differences between those states’ wetlands, too, with viable virus being found more frequently in Minnesotan samples than in Alaskan ones.
This kind of variation in virus infectivity with geography and specific environment will be an important avenue to explore in the future, says Himsworth, particularly for researchers who want to understand how future environmental changes may affect disease transmission or for studies that attempt to use environmental samples as part of virus surveillance. “I think the variability they even found within the study points to the fact that all of us, in our jurisdictions, need to get to know our own back yard.”
A.M. Ramey et al., “Influenza A viruses remain infectious for more than seven months in northern wetlands of North America,” Proc R Soc B, 20201680, 2020.


thescientist--2020-09-11--Predicting and Overcoming Resistance Using IsoPlexis' Single-Cell Intracellular Proteomic and Metabo

Predicting and Overcoming Resistance Using IsoPlexis' Single-Cell Intracellular Proteomic and Metabolomic Analysis Tools

Abig challenge in the field is that cancer cells develop resistance to targeted therapies , and researchers are striving to understand and characterize how these cancer cells are adapting in response to these therapies .
However , the inherent functional heterogeneity in cancer cells makes this challenging .
This heterogeneity complicates translating data from genetic profiles or responses into associated functional behaviors or phenotypes .
Although cancer cells have been characterized at the genetic and genomic levels , the functional mechanisms impacting protein-driven functional behaviors and activities can only be revealed through singlecell proteomics .
IsoPlexis ' single-cell proteomics has @ @ @ @ @ @ @ , leading to better strategies and combination therapies .
Single-cell intracellular proteomics and single-cell metabolomics combine to characterize drug resistance in melanoma cells The constant adaptation of cancer cells poses a great challenge for developing drug-based treatments , as cells that initially respond can quickly adopt drug-resistant states .
IsoPlexis ’ single-cell proteomics and multiomic technologies can help characterize the mechanisms and underlying factors driving drug resistance .
In a recent Nature Communications article , James Heath 's team from the California Institute of Technology described using predictive single-cell intracellular proteomics and metabolomics @ @ @ @ @ @ @ transitions to a final drug-resistant state via two distinct trajectories.1 When BRAFV600E mutant melanoma cells are treated with BRAF inhibitors , they quickly become drug tolerant .
To analyze what was happening within these cells to create a drug resistant state , Heath 's team treated these mutant cells with the BRAF inhibitor vemurafenib for varying durations and analyzed them using integrated single-cell intracellular proteomics and metabolomics .
Using IsoPlexis ' proteomic barcoding technology , the researchers characterized cellular heterogeneity within cell populations at different timepoints and quantitatively connected multiple timepoints to characterize @ @ @ @ @ @ @ .
Cellular state changes became prominent around day 3 , as most probed analytes exhibited a sharp but transitory increase in variance .
Indeed , all of the metabolic enzymes and signaling phosphoproteins , all metabolic regulators except for one , and all resistant state markers and regulators except for one displayed this phenomenon .
This information showed Heath 's team that cancer cell responses to a common stimulus may entail multiple divergent functional pathways while still resulting in the same genomic phenotype .
Understanding these functional adaptations allowed the team to predict @ @ @ @ @ @ @ overcome this adaptive resistance .
Proteomic analysis is instrumental in filling the knowledge gap left by genomics , especially at the single-cell level .
The IsoLight system from IsoPlexis enables researchers to ascertain true cellular functional phenotypes .
Going beyond the limited information provided by cell surface marker expression , IsoCode single-cell intracellular proteomic chips provide information on protein-protein interactions and pathway activation or deactivation , emphasizing changes in protein expression and alterations in phosphorylation profiles .
The IsoPlexis single-cell proteomics platform , the IsoLight , functions as a proteomic hub that uncovers @ @ @ @ @ @ @ cells .
IsoPlexis ' proteomics hub functionally phenotypes adaptive and innate immune cell populations and examines cell populations that shape the tumor microenvironment by looking at the secretome , intracellular proteome , and metabolome .
The platform is capable of identifying up to 32 different cytokines and intracellular proteins in a multiplexed manner at the singlecell level .
This is all combined with IsoPlexis ’ fully automated plug-and-play IsoSpeak software suite .
This powerful software analyzes data same day with intuitive and publication-ready advanced visualizations to help researchers further accelerate their therapies .
@ @ @ @ @ @ @ ’ intracellular proteome and metabolome technologies .
• Y. Su et al.
, “ Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line , ” Nat Commun , 11:2345 , 2020 .
This article is brought to you by IsoPlexis .
IsoPlexis is dedicated to accelerating the fight against cancer and a range of our toughest diseases by producing the world ’ s most precise , award-winning detection systems .
We succeed by merging top engineering with top researchers and clinicians to generate clear solutions to complex @ @ @ @ @ @

Abig challenge in the field is that cancer cells develop resistance to targeted therapies, and researchers are striving to understand and characterize how these cancer cells are adapting in response to these therapies. However, the inherent functional heterogeneity in cancer cells makes this challenging. This heterogeneity complicates translating data from genetic profiles or responses into associated functional behaviors or phenotypes. Although cancer cells have been characterized at the genetic and genomic levels, the functional mechanisms impacting protein-driven functional behaviors and activities can only be revealed through singlecell proteomics. IsoPlexis' single-cell proteomics has helped researchers overcome resistance to targeted inhibitors, leading to better strategies and combination therapies.
Single-cell intracellular proteomics and single-cell metabolomics combine to characterize drug resistance in melanoma cells
The constant adaptation of cancer cells poses a great challenge for developing drug-based treatments, as cells that initially respond can quickly adopt drug-resistant states. IsoPlexis’ single-cell proteomics and multiomic technologies can help characterize the mechanisms and underlying factors driving drug resistance.
In a recent Nature Communications article, James Heath's team from the California Institute of Technology described using predictive single-cell intracellular proteomics and metabolomics to identify how a cancer cell line transitions to a final drug-resistant state via two distinct trajectories.1 When BRAFV600E mutant melanoma cells are treated with BRAF inhibitors, they quickly become drug tolerant. To analyze what was happening within these cells to create a drug resistant state, Heath's team treated these mutant cells with the BRAF inhibitor vemurafenib for varying durations and analyzed them using integrated single-cell intracellular proteomics and metabolomics.
Using IsoPlexis' proteomic barcoding technology, the researchers characterized cellular heterogeneity within cell populations at different timepoints and quantitatively connected multiple timepoints to characterize dynamic heterogeneity on an individual cell level. Cellular state changes became prominent around day 3, as most probed analytes exhibited a sharp but transitory increase in variance. Indeed, all of the metabolic enzymes and signaling phosphoproteins, all metabolic regulators except for one, and all resistant state markers and regulators except for one displayed this phenomenon. This information showed Heath's team that cancer cell responses to a common stimulus may entail multiple divergent functional pathways while still resulting in the same genomic phenotype. Understanding these functional adaptations allowed the team to predict and develop an effective therapeutic combination to overcome this adaptive resistance.
Revealing true function with the IsoLight proteomic hub
Proteomic analysis is instrumental in filling the knowledge gap left by genomics, especially at the single-cell level. The IsoLight system from IsoPlexis enables researchers to ascertain true cellular functional phenotypes. Going beyond the limited information provided by cell surface marker expression, IsoCode single-cell intracellular proteomic chips provide information on protein-protein interactions and pathway activation or deactivation, emphasizing changes in protein expression and alterations in phosphorylation profiles.
The IsoPlexis single-cell proteomics platform, the IsoLight, functions as a proteomic hub that uncovers the true function from cancer and immune cells. IsoPlexis' proteomics hub functionally phenotypes adaptive and innate immune cell populations and examines cell populations that shape the tumor microenvironment by looking at the secretome, intracellular proteome, and metabolome. The platform is capable of identifying up to 32 different cytokines and intracellular proteins in a multiplexed manner at the singlecell level. This is all combined with IsoPlexis’ fully automated plug-and-play IsoSpeak software suite. This powerful software analyzes data same day with intuitive and publication-ready advanced visualizations to help researchers further accelerate their therapies.
Visit IsoPlexis.com for more information on IsoPlexis’ intracellular proteome and metabolome technologies.
Reference
Y. Su et al., “Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line,” Nat Commun, 11:2345, 2020.
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This article is brought to you by IsoPlexis. IsoPlexis is dedicated to accelerating the fight against cancer and a range of our toughest diseases by producing the world’s most precise, award-winning detection systems. We succeed by merging top engineering with top researchers and clinicians to generate clear solutions to complex patient response. https://isoplexis.com/


thescientist--2020-09-11--Field Research Sites Damaged as Fires Ravage West Coast

ABOVE : Fire lines helped save a barn in the Hastings Natural History Reservation in late August WALT KOENIG Since mid-August , at least 24 people have died in wildfires in California , Oregon , and Washington State , CNN reports .
Hundreds of homes and other structures have burned , including much of the towns of Phoenix and Talent in Oregon , and are consuming 900,000 acres in that state alone , according to an announcement from the governor ’ s office yesterday ( September 10 ) .
An estimated half a million Oregonians—more than 10 percent of the @ @ @ @ @ @ @ We have never seen this amount of uncontained fire across our state , ” Oregon Governor Kate Brown tells The New York Times .
Several colleges and universities , including Western Oregon University , have closed due to air quality issues caused by the fires .
University teaching and research sites have suffered in the fires , forcing staff and scientists to evacuate and destroying buildings and equipment .
Cal Poly ’ s Swanton Pacific Ranch , for example , a facility in California ’ s Santa Cruz County used to train students @ @ @ @ @ @ @ saw many of its structures destroyed in late August , according to a university statement .
Six reserves run by the University of California ( UC ) were also affected in August , according to a statement by the UC Natural Reserve System .
One of them , Hastings Natural History Reservation in the Carmel Valley , inland from Big Sur , now has the Dolan Fire to its south .
“ We ’ re getting three fires in the span of three weeks that are all coming at Hastings from different directions @ @ @ @ @ @ @ ecologist at Old Dominion University in Virginia who manages a long-term study of acorn woodpeckers who live in the reservation .
Walters , who was unable to make it to the field site in Hastings this summer due to the pandemic , says his graduate students and research assistants had to evacuate the site .
Normally , they track the behavior of groups of acorn woodpeckers that have been studied continuously at Hastings since 1968 .
The birds ’ behavior is very complex , he explains , and involves shared territories that revolve @ @ @ @ @ @ @ , an old-growth tree pocketed with numerous holes where the birds store acorns .
When fire burned parts of Hastings in late August , Walters says , his team was concerned the canopy of old-growth trees might burn , which would have been “ catastrophic.
” The fire remained at a low intensity , though , mainly burning dried grass .
Two dead trees that housed granaries did burn , including one that ’ s been followed since the beginning of the study more than 50 years ago .
It will be interesting @ @ @ @ @ @ @ the birds will react to their loss—by trying to make a new granary , for example , or by attempting to take over another group ’ s territory .
Another researcher whose field site at Hastings was hit by fire is Walter Koenig , a retired Cornell University professor who himself used to lead the acorn woodpecker project and who continues to study acorn production by oak trees around California .
A small part of his study site at Hastings burned , he says , and he had to evacuate from his house @ @ @ @ @ @ @ that burned in a wildfire five years ago—for six days .
Fire is disruptive for his work and has caused him to lose data in the past , he says .
Over the years he ’ s had study sites burn and has been cut off from others for some time due to fire-induced road closures .
“ I mean , it ’ s California and everything burns .
It ’ s what things do down here , ” he says .
“ So it ’ s not very surprising , but it @ @ @ @ @ @ @ makes it very difficult to carry on some of these really long-term studies of the sort that I like to do.
” Jennifer Hunter , Hastings ’ s residential director , says the site got lucky this time ; in contrast to some other UC reserves , all 26 of the Hastings buildings were spared , she notes , thanks in part to the efforts of neighbors and staff who cut fire lines around them .
And while the fire was undoubtedly disruptive to the site ’ s human users—she and her family @ @ @ @ @ @ @ for example—she says it ’ s “ great for the ecosystem.
” While she doubts the Dolan Fire will reach the reserve , Hunter adds that the lessons learned from the site ’ s experience in August will help in planning to keep the students and researchers who visit the site safe in future conflagrations .
“ Given climate change and given that these events may become more intense and more frequent than they have been in the past , we really need to do some serious reflecting on how we ’ re @ @ @

ABOVE: Fire lines helped save a barn in the Hastings Natural History Reservation in late August
WALT KOENIG
Since mid-August, at least 24 people have died in wildfires in California, Oregon, and Washington State, CNN reports. Hundreds of homes and other structures have burned, including much of the towns of Phoenix and Talent in Oregon, and are consuming 900,000 acres in that state alone, according to an announcement from the governor’s office yesterday (September 10). An estimated half a million Oregonians—more than 10 percent of the state’s population—have evacuated.
“We have never seen this amount of uncontained fire across our state,” Oregon Governor Kate Brown tells The New York Times.
Several colleges and universities, including Western Oregon University, have closed due to air quality issues caused by the fires. University teaching and research sites have suffered in the fires, forcing staff and scientists to evacuate and destroying buildings and equipment. Cal Poly’s Swanton Pacific Ranch, for example, a facility in California’s Santa Cruz County used to train students in agriculture and natural resource management, saw many of its structures destroyed in late August, according to a university statement.
Smoke from wildfires blankets the West Coast in this satellite image taken yesterday. MODIS Land Rapid Response Team, NASA GSFC
Six reserves run by the University of California (UC) were also affected in August, according to a statement by the UC Natural Reserve System. One of them, Hastings Natural History Reservation in the Carmel Valley, inland from Big Sur, now has the Dolan Fire to its south. “We’re getting three fires in the span of three weeks that are all coming at Hastings from different directions,” says Eric Walters, an ecologist at Old Dominion University in Virginia who manages a long-term study of acorn woodpeckers who live in the reservation.
Walters, who was unable to make it to the field site in Hastings this summer due to the pandemic, says his graduate students and research assistants had to evacuate the site. Normally, they track the behavior of groups of acorn woodpeckers that have been studied continuously at Hastings since 1968. The birds’ behavior is very complex, he explains, and involves shared territories that revolve around the use of a granary—for them, an old-growth tree pocketed with numerous holes where the birds store acorns.
When fire burned parts of Hastings in late August, Walters says, his team was concerned the canopy of old-growth trees might burn, which would have been “catastrophic.” The fire remained at a low intensity, though, mainly burning dried grass. Two dead trees that housed granaries did burn, including one that’s been followed since the beginning of the study more than 50 years ago. It will be interesting to see, he says, how the birds will react to their loss—by trying to make a new granary, for example, or by attempting to take over another group’s territory.
A burned station Walters’s team uses to record the movements of tagged birds TORI BAKLEY
Another researcher whose field site at Hastings was hit by fire is Walter Koenig, a retired Cornell University professor who himself used to lead the acorn woodpecker project and who continues to study acorn production by oak trees around California. A small part of his study site at Hastings burned, he says, and he had to evacuate from his house near the site—which itself replaced a house that burned in a wildfire five years ago—for six days.
Fire is disruptive for his work and has caused him to lose data in the past, he says. Over the years he’s had study sites burn and has been cut off from others for some time due to fire-induced road closures. “I mean, it’s California and everything burns. It’s what things do down here,” he says. “So it’s not very surprising, but it’s a big environmental factor that makes it very difficult to carry on some of these really long-term studies of the sort that I like to do.”
Jennifer Hunter, Hastings’s residential director, says the site got lucky this time; in contrast to some other UC reserves, all 26 of the Hastings buildings were spared, she notes, thanks in part to the efforts of neighbors and staff who cut fire lines around them. And while the fire was undoubtedly disruptive to the site’s human users—she and her family had to evacuate her on-site home, for example—she says it’s “great for the ecosystem.”
While she doubts the Dolan Fire will reach the reserve, Hunter adds that the lessons learned from the site’s experience in August will help in planning to keep the students and researchers who visit the site safe in future conflagrations. “Given climate change and given that these events may become more intense and more frequent than they have been in the past, we really need to do some serious reflecting on how we’re preparing.”


thescientist--2020-09-11--Scientists Voice Concerns over Russian COVID-19 Vaccine Study

ABOVE : The Russian vaccine relies on a human adenovirus to prime the body ’ s immune response to SARS-CoV-2 .
© ISTOCK.COM , CHRISTOPH BURGSTEDT The first data detailing Russia ’ s COVID-19 vaccine—nicknamed Sputnik—was published last week ( September 4 ) in The Lancet .
Almost immediately , other scientists began to call attention to unlikely patterns in the data , asking for raw numbers to verify the study ’ s conclusions .
Enrico Bucci , a systems biologist and bioethicist at Temple University , published an open letter on his blog September 7 to draw The Lancet @ @ @ @ @ @ @ .
While he stresses that the letter is not an allegation , “ the presentation of the data raises several concerns which require access to the original data to fully investigate.
” The study reports results of Russia ’ s Phase 1/2 clinical trial to assess the safety and effectiveness of its vaccine candidate , carried out by Moscow ’ s Gamaleya Institute .
The tests took place between June and July of this year with 76 participants , and researchers trialed two versions of a human adenovirus vector–based immunization , an approach @ @ @ @ @ @ @ Oxford joint initiative .
The benign virus contains the gene for the SARS-CoV-2 spike protein that when expressed primes the immune system to recognize the virus as a threat .
See “ Vector-Based Vaccines Come to the Fore in the COVID-19 Pandemic ” Researchers carried out two simultaneous studies in two different hospitals , each of which involved 38 people involved in either a Phase1 or Phase 2 trial .
During the Phase 1 portion , nine participants received the human adenovirus 26 ( Ad26 ) vector and another nine received the adenovirus @ @ @ @ @ @ @ Phase 2 , 20 patients were given an initial dose of the Ad26 version followed by a booster of Ad5 .
The results show that all patients generated antibodies to the virus after 28 days , although the levels were not as high as those seen in other studies , Chemistry World reports .
Side effects were said to be common , but mild .
Based on the results of this trial , Russia recently began a Phase 3 trial involving 40,000 participants .
Roughly 31,000 people have already been recruited to take @ @ @ @ @ @ @ , Health Minister Mikhail Murashko tells Reuters .
Even without the results of this latest trial , Russia plans to ramp up production of a finished product for distribution beginning this month , a move that has alarmed scientists worldwide .
Bucci and the other cosigners of the open letter noted “ strange duplicated patterns in the data , among different groups , observing different variables , ” Chemistry World reports .
For example , measurements of CD4 T cell counts for nine people in the study closely matched a different set of @ @ @ @ @ @ @ cells measured .
In other instances , multiple participants had identical antibody levels .
“ It ’ s like you enter a room with nine people and you add their ages together and find that that number is exactly the same as the combined weight of those people , ” Bucci tells Chemistry World .
“ It is strange .
But we don ’ t have access to the data and we can ’ t really assess what is going on.
” In addition , the study design was such that the statistical @ @ @ @ @ @ @ “ They tested six different formulations , basically split among six groups of volunteers , ” Bucci adds .
“ It is like six independent studies in a single article.
” Bucci is not the only one to stress that the study ’ s conclusions are tentative at best .
Luke O ’ Neill , an immunologist at Trinity College Dublin , tells Chemistry World that the immune response appeared weak , and that the study lacked a control group .
Saad Shakir , the director of the Drug Safety Research Unit ( @ @ @ @ @ @ @ more plainly .
“ It is very preliminary .
That ’ s the bottom line .
No one has demonstrated that these [ antibody ] elevations will translate into protecting people ” In response to the letter ’ s points , Denis Logunov , a deputy director at the Gamaleya Institute , refuted the claims , stating that he provided all the raw data to the journal ahead of publication even if they were not included in the paper ’ s supplementary material .
“ The published results are authentic and accurate and @ @ @ @ @ @ @ Lancet , ” Logunov says in a statement to Reuters .
“ We presented specifically the data that was produced [ by the trial ] , not the data that is supposed to please Italian experts , ” he adds .
Bucci and a number of other signatories are from Italy .
At least one of the paper ’ s reviewers has defended his analysis of the data .
In an email to Reuters , Naor Bar-Zeev , an epidemiologist at John Hopkins Bloomberg School of Public Health , says that “ the @ @ @ @ @ @ @ different to those seen with other AdV vectored products .
Bottom line , I saw no reason to doubt the legitimacy of these results over others I have read and reviewed.
” A Lancet spokesperson has stated to Reuters that they are monitoring the situation and encouraging the authors of the Russian study to respond to questions raised in the open letter .

ABOVE: The Russian vaccine relies on a human adenovirus to prime the body’s immune response to SARS-CoV-2.
© ISTOCK.COM, CHRISTOPH BURGSTEDT
The first data detailing Russia’s COVID-19 vaccine—nicknamed Sputnik—was published last week (September 4) in The Lancet. Almost immediately, other scientists began to call attention to unlikely patterns in the data, asking for raw numbers to verify the study’s conclusions.
Enrico Bucci, a systems biologist and bioethicist at Temple University, published an open letter on his blog September 7 to draw The Lancet’s attention to suspected data manipulation. While he stresses that the letter is not an allegation, “the presentation of the data raises several concerns which require access to the original data to fully investigate.”
The study reports results of Russia’s Phase 1/2 clinical trial to assess the safety and effectiveness of its vaccine candidate, carried out by Moscow’s Gamaleya Institute. The tests took place between June and July of this year with 76 participants, and researchers trialed two versions of a human adenovirus vector–based immunization, an approach similar to that of the AstraZeneca/University of Oxford joint initiative. The benign virus contains the gene for the SARS-CoV-2 spike protein that when expressed primes the immune system to recognize the virus as a threat.
Researchers carried out two simultaneous studies in two different hospitals, each of which involved 38 people involved in either a Phase1 or Phase 2 trial. During the Phase 1 portion, nine participants received the human adenovirus 26 (Ad26) vector and another nine received the adenovirus 5 (Ad5) vector. In Phase 2, 20 patients were given an initial dose of the Ad26 version followed by a booster of Ad5. The results show that all patients generated antibodies to the virus after 28 days, although the levels were not as high as those seen in other studies, Chemistry World reports. Side effects were said to be common, but mild.
Based on the results of this trial, Russia recently began a Phase 3 trial involving 40,000 participants. Roughly 31,000 people have already been recruited to take part since its launch on August 26, Health Minister Mikhail Murashko tells Reuters. Even without the results of this latest trial, Russia plans to ramp up production of a finished product for distribution beginning this month, a move that has alarmed scientists worldwide.
Bucci and the other cosigners of the open letter noted “strange duplicated patterns in the data, among different groups, observing different variables,” Chemistry World reports. For example, measurements of CD4 T cell counts for nine people in the study closely matched a different set of nine patients who had their CD8 T cells measured. In other instances, multiple participants had identical antibody levels.
“It’s like you enter a room with nine people and you add their ages together and find that that number is exactly the same as the combined weight of those people,” Bucci tells Chemistry World. “It is strange. But we don’t have access to the data and we can’t really assess what is going on.”
In addition, the study design was such that the statistical power to draw conclusions is limited. “They tested six different formulations, basically split among six groups of volunteers,” Bucci adds. “It is like six independent studies in a single article.”
Bucci is not the only one to stress that the study’s conclusions are tentative at best.
Luke O’Neill, an immunologist at Trinity College Dublin, tells Chemistry World that the immune response appeared weak, and that the study lacked a control group. Saad Shakir, the director of the Drug Safety Research Unit (DSRU) in the UK, spoke more plainly. “It is very preliminary. That’s the bottom line. No one has demonstrated that these [antibody] elevations will translate into protecting people”
In response to the letter’s points, Denis Logunov, a deputy director at the Gamaleya Institute, refuted the claims, stating that he provided all the raw data to the journal ahead of publication even if they were not included in the paper’s supplementary material. “The published results are authentic and accurate and were examined by five reviewers at The Lancet,” Logunov says in a statement to Reuters. “We presented specifically the data that was produced [by the trial], not the data that is supposed to please Italian experts,” he adds. Bucci and a number of other signatories are from Italy.
At least one of the paper’s reviewers has defended his analysis of the data. In an email to Reuters, Naor Bar-Zeev, an epidemiologist at John Hopkins Bloomberg School of Public Health, says that “the results are plausible, and not very different to those seen with other AdV vectored products. Bottom line, I saw no reason to doubt the legitimacy of these results over others I have read and reviewed.”
A Lancet spokesperson has stated to Reuters that they are monitoring the situation and encouraging the authors of the Russian study to respond to questions raised in the open letter.


thescientist--2020-09-11--Springer Nature and ResearchGate Expand Content Sharing

Springer Nature and ResearchGate announced plans on September 9 for a long-term partnership to share the publishers ’ papers on the networking site .
This agreement is an extension of a pilot article-sharing project that began in March 2019 .
Through that initiative , content from 23 Nature-branded journals was automatically uploaded onto authors ’ ResearchGate platforms .
In July 2019 , the pilot was extended to include content from 18 additional titles from the publisher ’ s Springer collection .
See “ Springer Nature Now Shares Select Papers on ResearchGate ” Findings from the pilot were released in a @ @ @ @ @ @ @ that approximately 50,000 articles were uploaded during the program .
Comparisons of article retrievals before and after they were shared on ResearchGate revealed that papers uploaded ( syndicated ) to the platform were downloaded between 0.6–19.5 more often .
And in a survey of close to 700 authors , 90 percent reported viewing the partnership as a positive one .
Under the new agreement , four times as many Springer Nature journals will be available through ResearchGate ’ s platform .
There is a notable change : During the pilot , users without @ @ @ @ @ @ @ will no longer be possible .
Instead , non-authorized users will have access to previews , which includes the first page of a paper , along with figures and metadata .
Authors will , however , be allowed to post preprints and other earlier versions of their articles , as long as licensing agreements permit them to be shared .
( ResearchGate authenticates those with subscription access using IP addresses and information on users ’ profiles . )
Lisa Hinchliffe , a professor and the coordinator of information literacy services at the University @ @ @ @ @ @ @ , in recent years , there has been a lot of discussion among both libraries and publishers about how to get content to readers .
A platform such as ResearchGate , she says , provides a new way of getting content to scholars .
In addition to getting a bump in readership , “ by being able to work with ResearchGate , to identify the institutional affiliation of readers , [ Springer Nature ] is able to leverage the library subscription—but into a different platform that is neither theirs nor the libraries ’ @ @ @ @ @ @ @ can then tell libraries that their subscription dollars are being well spent because scholars are reading the work.
” ResearchGate , which provides academics with a platform to share their articles , has a complicated relationship with scholarly publishers .
Elsevier and the American Chemical Society have sued the platform , alleging that it was infringing on publishers ’ copyrights by freely disseminating paywalled works .
The two publishers are also part of a group known as the Coalition for Responsible Sharing , which has taken a stand against ResearchGate and issues takedown @ @ @ @ @ @ @ .
See “ Major Publishers File Second Lawsuit Against ResearchGate ” In May , one of the group ’ s largest members , Wiley , announced that it would be entering into a cooperation agreement with ResearchGate and withdrew from the coalition .
Following this announcement , the Coalition for Responsible Sharing released a statement in which they said the cooperation proposals by ResearchGate did not address their concerns , and that copyright-infringing posts continued to be added to the site .
“ An average of 130,000 articles have continued to be added @ @ @ @ @ @ @ percent of which infringe copyright , ” they wrote .
“ To date , Coalition for Responsible Sharing members have sent nearly 450,000 takedown notices to ResearchGate for copyright infringing content it distributes.
” Most publishers have not taken a public stance on ResearchGate .
“ I would not be surprised if in the next couple years , we see publishers who had taken ‘ a wait-and-see approach ’ beginning to choose their path , ” Hinchliffe says .
She adds that Springer Nature ’ s partnership with ResearchGate is paving one of @ @ @ @ @ @ @ take .
“ Springer Nature and ResearchGate entered this collaborative content syndication pilot with the aim of better supporting the researchers we serve , ” Sören Hofmayer , a cofounder of ResearchGate , said this week in the press release about the newly expanded partnership .
“ We hope it will encourage other actors in the scholarly communication ecosystem to join us to keep innovating to better support researchers , together.
” COI statement : Diana Kwon has received payments from Springer Nature as a freelance reporter for Scientific American and Nature , @ @ @ @ @ @ @ .

ABOVE: © ISTOCK.COM, BILGIC
Springer Nature and ResearchGate announced plans on September 9 for a long-term partnership to share the publishers’ papers on the networking site.
This agreement is an extension of a pilot article-sharing project that began in March 2019. Through that initiative, content from 23 Nature-branded journals was automatically uploaded onto authors’ ResearchGate platforms. In July 2019, the pilot was extended to include content from 18 additional titles from the publisher’s Springer collection.
See “Springer Nature Now Shares Select Papers on ResearchGate”
Findings from the pilot were released in a white paper this week, which reports that approximately 50,000 articles were uploaded during the program. Comparisons of article retrievals before and after they were shared on ResearchGate revealed that papers uploaded (syndicated) to the platform were downloaded between 0.6–19.5 more often. And in a survey of close to 700 authors, 90 percent reported viewing the partnership as a positive one.
Under the new agreement, four times as many Springer Nature journals will be available through ResearchGate’s platform. There is a notable change: During the pilot, users without subscriptions could access read-only versions of articles—this will no longer be possible. Instead, non-authorized users will have access to previews, which includes the first page of a paper, along with figures and metadata. Authors will, however, be allowed to post preprints and other earlier versions of their articles, as long as licensing agreements permit them to be shared. (ResearchGate authenticates those with subscription access using IP addresses and information on users’ profiles.)
Lisa Hinchliffe, a professor and the coordinator of information literacy services at the University of Illinois at Urbana-Champaign, notes that, in recent years, there has been a lot of discussion among both libraries and publishers about how to get content to readers. A platform such as ResearchGate, she says, provides a new way of getting content to scholars. In addition to getting a bump in readership, “by being able to work with ResearchGate, to identify the institutional affiliation of readers, [Springer Nature] is able to leverage the library subscription—but into a different platform that is neither theirs nor the libraries’,” Hinchliffe says. “They can then tell libraries that their subscription dollars are being well spent because scholars are reading the work.”
ResearchGate, which provides academics with a platform to share their articles, has a complicated relationship with scholarly publishers. Elsevier and the American Chemical Society have sued the platform, alleging that it was infringing on publishers’ copyrights by freely disseminating paywalled works. The two publishers are also part of a group known as the Coalition for Responsible Sharing, which has taken a stand against ResearchGate and issues takedown notices for articles identified as breaching copyright.
See “Major Publishers File Second Lawsuit Against ResearchGate”
In May, one of the group’s largest members, Wiley, announced that it would be entering into a cooperation agreement with ResearchGate and withdrew from the coalition.
Following this announcement, the Coalition for Responsible Sharing released a statement in which they said the cooperation proposals by ResearchGate did not address their concerns, and that copyright-infringing posts continued to be added to the site. “An average of 130,000 articles have continued to be added to ResearchGate each month, approximately 45 percent of which infringe copyright,” they wrote. “To date, Coalition for Responsible Sharing members have sent nearly 450,000 takedown notices to ResearchGate for copyright infringing content it distributes.”
Most publishers have not taken a public stance on ResearchGate. “I would not be surprised if in the next couple years, we see publishers who had taken ‘a wait-and-see approach’ beginning to choose their path,” Hinchliffe says. She adds that Springer Nature’s partnership with ResearchGate is paving one of the potential routes these other publishers might take.
“Springer Nature and ResearchGate entered this collaborative content syndication pilot with the aim of better supporting the researchers we serve,” Sören Hofmayer, a cofounder of ResearchGate, said this week in the press release about the newly expanded partnership. “We hope it will encourage other actors in the scholarly communication ecosystem to join us to keep innovating to better support researchers, together.”
COI statement: Diana Kwon has received payments from Springer Nature as a freelance reporter for Scientific American and Nature, editorially independent publications owned by the publisher.


thescientist--2020-09-11--The Scientist's LabTalk Podcast - Episode 1

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thescientist--2020-09-11--Poor Sleep Linked with Future Amyloid-Beta Build Up

There ’ s evidence in people and animals that short-term sleep deprivation can change the levels of amyloid-β , a peptide that can accumulate in the aging brain and cause Alzheimer ’ s disease .
Scientists now show long-term consequences may also result from sustained poor sleep .
In a study published September 3 in Current Biology , researchers found that healthy individuals with lower-quality sleep were more likely to have amyloid-β accumulation in the brain years later .
The study could not say whether poor sleep caused amyloid-β accumulation or vice versa , but the authors say that sleep @ @ @ @ @ @ @ future amyloid-β levels .
“ Traditionally , sleep disruptions have been accepted as a symptom of Alzheimer ’ s disease , ” says Ksenia Kastanenka , a neuroscientist at Massachusetts General Hospital who was not involved in the work .
Her group showed in 2017 that improving sleep in a mouse model of Alzheimer ’ s disease , in which the animals ’ slow wave sleep is disrupted as it usually is in people with the disease , halted disease progression .
Collectively , the results from these studies and others raise the @ @ @ @ @ @ @ not an artifact of disease progression , but actually are active contributors , if not a cause , ” she says , hinting at the prospect of using these sleep measures as a biomarker for Alzheimer ’ s disease .
As a graduate student at the University of California , Berkeley , Joseph Winer , who is now a postdoc at Stanford University , and his colleagues were interested in whether or not sleep could predict how the brain changes over time .
They collaborated with the team behind the Berkeley Aging Cohort @ @ @ @ @ @ @ 32 cognitively healthy adults averaging about 75 years of age .
They participated in a sleep study , then had periodic cognitive assessments and between two and five positron emission tomography ( PET ) scans to check for the presence of amyloid-β in their brains for an average of about four years after the sleep study .
The researchers found at their baseline PET scan , which happened within six months of their sleep study , that 20 of the 32 participants already had some amyloid-β accumulation , which was not unexpected based @ @ @ @ @ @ @ showed that both slow wave sleep , an indicator of depth of sleep , and sleep efficiency , the amount of time sleeping compared to time in bed , were both predictive of the rate of amyloid change several years later .
In other words , people with lower levels of slow wave sleep and sleep efficiency were more likely to have faster amyloid build up .
The subjects all remained cognitively healthy over the duration of the study , says Winer .
“ We do expect that they ’ re at higher @ @ @ @ @ @ @ their lifetime because of the amyloid plaque.
” The strengths of the study include the well-characterized participants with detailed sleep assessments , as well as cognitive testing and longitudinal amyloid PET imaging , says Brendan Lucey , a sleep neurologist at Washington University in St. Louis who did not participate in the work .
There are still open questions about the link between sleep and amyloid deposition over time .
“ Amyloid accumulation on PET increases at different rates in amyloid-negative and amyloid-positive individuals , and even within amyloid-positive individuals , ” Lucey @ @ @ @ @ @ @ ’ starting amyloid [ levels ] , we don ’ t know if some participants would have been more likely to have increased amyloid compared to others , independent of sleep.
” “ It is very hard to untangle this question of baselines , ” acknowledges Winer .
Because the sleep measures the team identified in the study are related to amyloid levels , to actually tease apart the effect of sleep quality on amyloid deposition and vice versa , it ’ d be necessary to study people starting as early as their @ @ @ @ @ @ @ less likely to have amyloid accumulation , he says .
This study is “ a great start , ” David Holtzman , a neurologist and collaborator of Lucey at Washington University in St. Louis who did not participate in the work , tells The Scientist .
In addition to controlling for the amount of amyloid deposition that is present in a subject ’ s brain at the beginning of the study , it would be important to see if the findings bear out in larger numbers of people and what role genetic factors @ @ @ @ @ @ @ down the road is to test the idea in some sort of a treatment paradigm , ” Holtzman adds .
“ You can do something to improve the quality of sleep or increase slow wave sleep , and then determine if it actually slows down the onset of Alzheimer ’ s disease clinically .
”

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There’s evidence in people and animals that short-term sleep deprivation can change the levels of amyloid-β, a peptide that can accumulate in the aging brain and cause Alzheimer’s disease. Scientists now show long-term consequences may also result from sustained poor sleep. In a study published September 3 in Current Biology, researchers found that healthy individuals with lower-quality sleep were more likely to have amyloid-β accumulation in the brain years later. The study could not say whether poor sleep caused amyloid-β accumulation or vice versa, but the authors say that sleep could be an indicator of present and future amyloid-β levels.
“Traditionally, sleep disruptions have been accepted as a symptom of Alzheimer’s disease,” says Ksenia Kastanenka, a neuroscientist at Massachusetts General Hospital who was not involved in the work. Her group showed in 2017 that improving sleep in a mouse model of Alzheimer’s disease, in which the animals’ slow wave sleep is disrupted as it usually is in people with the disease, halted disease progression.
Collectively, the results from these studies and others raise the possibility that “sleep rhythm disruptions are not an artifact of disease progression, but actually are active contributors, if not a cause,” she says, hinting at the prospect of using these sleep measures as a biomarker for Alzheimer’s disease.
As a graduate student at the University of California, Berkeley, Joseph Winer, who is now a postdoc at Stanford University, and his colleagues were interested in whether or not sleep could predict how the brain changes over time. They collaborated with the team behind the Berkeley Aging Cohort Study, which includes a group of 32 cognitively healthy adults averaging about 75 years of age. They participated in a sleep study, then had periodic cognitive assessments and between two and five positron emission tomography (PET) scans to check for the presence of amyloid-β in their brains for an average of about four years after the sleep study.
The researchers found at their baseline PET scan, which happened within six months of their sleep study, that 20 of the 32 participants already had some amyloid-β accumulation, which was not unexpected based on their average age. They also showed that both slow wave sleep, an indicator of depth of sleep, and sleep efficiency, the amount of time sleeping compared to time in bed, were both predictive of the rate of amyloid change several years later. In other words, people with lower levels of slow wave sleep and sleep efficiency were more likely to have faster amyloid build up.
The subjects all remained cognitively healthy over the duration of the study, says Winer. “We do expect that they’re at higher risk for developing Alzheimer’s in their lifetime because of the amyloid plaque.”
The strengths of the study include the well-characterized participants with detailed sleep assessments, as well as cognitive testing and longitudinal amyloid PET imaging, says Brendan Lucey, a sleep neurologist at Washington University in St. Louis who did not participate in the work.
There are still open questions about the link between sleep and amyloid deposition over time. “Amyloid accumulation on PET increases at different rates in amyloid-negative and amyloid-positive individuals, and even within amyloid-positive individuals,” Lucey explains. “Without adjusting for participants’ starting amyloid [levels], we don’t know if some participants would have been more likely to have increased amyloid compared to others, independent of sleep.”
“It is very hard to untangle this question of baselines,” acknowledges Winer. Because the sleep measures the team identified in the study are related to amyloid levels, to actually tease apart the effect of sleep quality on amyloid deposition and vice versa, it’d be necessary to study people starting as early as their fifties, when they’re much less likely to have amyloid accumulation, he says.
This study is “a great start,” David Holtzman, a neurologist and collaborator of Lucey at Washington University in St. Louis who did not participate in the work, tells The Scientist. In addition to controlling for the amount of amyloid deposition that is present in a subject’s brain at the beginning of the study, it would be important to see if the findings bear out in larger numbers of people and what role genetic factors play.
“The most important question down the road is to test the idea in some sort of a treatment paradigm,” Holtzman adds. “You can do something to improve the quality of sleep or increase slow wave sleep, and then determine if it actually slows down the onset of Alzheimer’s disease clinically.”
J.R. Winer et al., “Sleep disturbance forecasts β-amyloid accumulation across subsequent years,” Current Biology, doi:10.1016/j.cub.2020.08.017, 2020.