thescientist--2020-11-05--Animal Movement Data Reveal Effects of Climate Change in Arctic

ABOVE : This female Peregrine was tracked from its breeding site on the Popigai River in Arctic Russia to its wintering range on the Baluchestan coast of the Arabian Sea in Pakistan over three successive seasons .
ANDREW DIXON The Arctic is warming faster than any region of Earth , with potentially serious consequences for the animals scattered across its 5.5 million square miles of ice , open sea , boreal forest , and naked tundra .
To make sense of how the region is shifting and what that will mean for wildlife , scientists are taking a cue from @ @ @ @ @ @ @ resources—in this case , their animal tracking research efforts .
The result is a new ecological tool for studying climate change at the planet ’ s northern pole .
The Arctic Animal Movement Archive ( AAMA ) , detailed in a report published today ( November 5 ) in Science , contains more than 200 studies contributed by polar research groups and scientists from national , regional , and First Nations governments .
Housed on Movebank , an online platform hosted by the Max Planck Institute of Animal Behavior , the database includes @ @ @ @ @ @ @ more than 8,000 individual animals—birds , wolves , bears , caribou , moose , whales , and seals , among others—collected over the last three decades .
The cumulative power behind this large dataset is allowing scientists to analyze the ecological impacts of long-term changes in weather and habitat on a panarctic scale .
Gil Bohrer , an environmental engineer at the Ohio State University and a coauthor of the new report , spoke to The Scientist about what this unprecedented effort can tell us about how species adapt to a warming world @ @ @ @ @ @ @ by saying that the Arctic is entering a new ecological state , and that the consequences of that could be alarming .
What does that look like ?
Gil Bohrer : It ’ s well demonstrated that with global climate change , the Arctic is experiencing a much faster rate of change than any other ecosystem on Earth , more than twice the global average .
We already see parts of the Arctic that are greening and parts of the Arctic that are browning .
The northern edge of the boreal forest is @ @ @ @ @ @ @ is decreasing every year .
On top of that , the Arctic didn ’ t have many people .
Now there is mining , coal and gas industry , and tourism .
This is all the baseline of our work , and we know there is a very extreme environmental change in the Arctic .
Everything put together—human activity , climate change , changes to patterns of snow and rain and temperature , and the timing of the seasons—we expect that all of that will affect the ecology of the animals in the @ @ @ @ @ @ @ demonstrated that things are happening .
We have seen changes in animal distributions , changes in the [ seasonal ] timing of migration , changes in the food and vegetation .
TS : What role can big data play in furthering our understanding of climate change in this area ?
GB : Climate change is a very slow phenomenon .
It ’ s a very large-scale phenomenon .
And especially with animal movement data that ’ s driven by tagged animals , it is extremely hard to get the long-term , large-scale picture @ @ @ @ @ @ @ scientists tagging the same population .
The other challenge is that the climate is a complicated pattern .
It ’ s many different interacting physical drivers .
What we do with the archive is join the efforts of many , many scientists from many countries , many agencies , and over many years .
We are able to compile that large-scale , long-term dataset that ’ s been elusive for researchers of animal movement working on their own funded study .
TS : How did you seek out partners , and how long @ @ @ @ @ @ @ new archive ?
GB : Movebank is a Max Planck–operated database .
It ’ s a tool for you to manage and visualize your data , kind of like your own Facebook account of animal movement .
.
.
.
[ For the AAMA ] , I started pushing a much more ambitious vision .
Why are we only working amongst ourselves and with our immediate collaborators ?
Can we expand it ?
Can we make a huge Arctic animal movement archive with everyone ?
Among our team , we know of many @ @ @ @ @ @ @ that don ’ t have their data in Movebank .
We asked them if they wanted to come on the platform , a kind of ‘ friend brings friend ’ thing , and we spread among the whole community as far as we could .
It took about two years , and I think the biggest challenge was to convince people that nobody is taking away data and nobody has to share anything they ’ re not comfortable with .
We don ’ t have all the Arctic data , of course , @ @ @ @ @ @ @ of it .
Right now , about forty percent of the data is open and public , and the archive is growing .
A lot of the existing collaborators are choosing to open their data .
TS : The paper includes a few case studies using the archive data .
Can you walk us through one of these studies and what was found ?
GB : Another thing that the archive facilitates that is not easy to do is a multi-species study .
Any individual researcher is limited by the number of tags @ @ @ @ @ @ @ a bear is not like trapping a caribou .
So a study that involves all the trophic levels of the ecosystem from the herbivore to the predators is very , very rare .
We studied how jittery [ animals are ] , how much more movement you get per day , as a .
.
.
function of the temperature and precipitation each season .
Very predictably , they don ’ t like it when it snows , they tend to move less [ in winter ] .
Strangely , they don ’ @ @ @ @ @ @ @ .
But the interesting find was that increased temperature in the summer is having very different influences on herbivores and predators .
[ Editor ’ s note : The study included caribou , moose , bears , and wolves . ]
Two of the three predators were moving less , and two of the three herbivores were moving more when it ’ s warmer .
Since movement takes energy—and we assume in ecology the need to optimize energy—there must be more challenges when higher temperatures drive them to move more .
This is @ @ @ @ @ @ @ you can get into what ’ s called a trophic mismatch .
In this case , it benefits the predator and penalizes the herbivore , which will throw things out of whack .
TS : What is your ultimate vision for the archive ?
GB : We really want the archive to keep growing .
We want anyone that ’ s doing animal research in the Arctic to consider participating in the archive , knowing that it will preserve the data for posterity , make it discoverable , allow people to collaborate with @ @ @ @ @ @ @ .
Editor ’ s note : The interview was edited for brevity .

ABOVE: This female Peregrine was tracked from its breeding site on the Popigai River in Arctic Russia to its wintering range on the Baluchestan coast of the Arabian Sea in Pakistan over three successive seasons.
ANDREW DIXON
The Arctic is warming faster than any region of Earth, with potentially serious consequences for the animals scattered across its 5.5 million square miles of ice, open sea, boreal forest, and naked tundra. To make sense of how the region is shifting and what that will mean for wildlife, scientists are taking a cue from the caribou, banding together and pooling resources—in this case, their animal tracking research efforts. The result is a new ecological tool for studying climate change at the planet’s northern pole.
Gil Bohrer, an environmental engineer at the Ohio State University, installs a sensor on a meteorological tower Gil Bohrer
The Arctic Animal Movement Archive (AAMA), detailed in a report published today (November 5) in Science, contains more than 200 studies contributed by polar research groups and scientists from national, regional, and First Nations governments. Housed on Movebank, an online platform hosted by the Max Planck Institute of Animal Behavior, the database includes movement information from almost 100 species and more than 8,000 individual animals—birds, wolves, bears, caribou, moose, whales, and seals, among others—collected over the last three decades. The cumulative power behind this large dataset is allowing scientists to analyze the ecological impacts of long-term changes in weather and habitat on a panarctic scale.
Gil Bohrer, an environmental engineer at the Ohio State University and a coauthor of the new report, spoke to The Scientist about what this unprecedented effort can tell us about how species adapt to a warming world.
The Scientist: The paper opens by saying that the Arctic is entering a new ecological state, and that the consequences of that could be alarming. What does that look like?
Gil Bohrer: It’s well demonstrated that with global climate change, the Arctic is experiencing a much faster rate of change than any other ecosystem on Earth, more than twice the global average. We already see parts of the Arctic that are greening and parts of the Arctic that are browning. The northern edge of the boreal forest is creeping northward, the sea ice extent is decreasing every year. On top of that, the Arctic didn’t have many people. Now there is mining, coal and gas industry, and tourism. This is all the baseline of our work, and we know there is a very extreme environmental change in the Arctic.
Everything put together—human activity, climate change, changes to patterns of snow and rain and temperature, and the timing of the seasons—we expect that all of that will affect the ecology of the animals in the Arctic. It’s already been demonstrated that things are happening. We have seen changes in animal distributions, changes in the [seasonal] timing of migration, changes in the food and vegetation.
A map showing the seasonal movement of several groups of animals using Arctic Animal Movement Archive data Roland Kays, NC State University
TS: What role can big data play in furthering our understanding of climate change in this area?
GB: Climate change is a very slow phenomenon. It’s a very large-scale phenomenon. And especially with animal movement data that’s driven by tagged animals, it is extremely hard to get the long-term, large-scale picture of things. You need generations of scientists tagging the same population. The other challenge is that the climate is a complicated pattern. It’s many different interacting physical drivers. What we do with the archive is join the efforts of many, many scientists from many countries, many agencies, and over many years. We are able to compile that large-scale, long-term dataset that’s been elusive for researchers of animal movement working on their own funded study.
TS: How did you seek out partners, and how long did it take to grow out this new archive?
GB: Movebank is a Max Planck–operated database. It’s a tool for you to manage and visualize your data, kind of like your own Facebook account of animal movement. . . . [For the AAMA], I started pushing a much more ambitious vision. Why are we only working amongst ourselves and with our immediate collaborators? Can we expand it? Can we make a huge Arctic animal movement archive with everyone? Among our team, we know of many other people [doing this work] that don’t have their data in Movebank. We asked them if they wanted to come on the platform, a kind of ‘friend brings friend’ thing, and we spread among the whole community as far as we could.
Coauthor Laura Prugh, a wildlife community ecologist at the University of Washington, radio-collaring a grey wolf in Denali National Park and Preserve Troy Cambier
It took about two years, and I think the biggest challenge was to convince people that nobody is taking away data and nobody has to share anything they’re not comfortable with. We don’t have all the Arctic data, of course, but we have a very sizable chunk of it. Right now, about forty percent of the data is open and public, and the archive is growing. A lot of the existing collaborators are choosing to open their data.
TS: The paper includes a few case studies using the archive data. Can you walk us through one of these studies and what was found?
GB: Another thing that the archive facilitates that is not easy to do is a multi-species study. Any individual researcher is limited by the number of tags and by their in-home knowledge. Trapping a bear is not like trapping a caribou. So a study that involves all the trophic levels of the ecosystem from the herbivore to the predators is very, very rare.
We studied how jittery [animals are], how much more movement you get per day, as a . . . function of the temperature and precipitation each season. Very predictably, they don’t like it when it snows, they tend to move less [in winter]. Strangely, they don’t care about rain in the summer.
But the interesting find was that increased temperature in the summer is having very different influences on herbivores and predators. [Editor’s note: The study included caribou, moose, bears, and wolves.] Two of the three predators were moving less, and two of the three herbivores were moving more when it’s warmer. Since movement takes energy—and we assume in ecology the need to optimize energy—there must be more challenges when higher temperatures drive them to move more. This is an indication that as warming intensifies, you can get into what’s called a trophic mismatch. In this case, it benefits the predator and penalizes the herbivore, which will throw things out of whack.
TS: What is your ultimate vision for the archive?
GB: We really want the archive to keep growing. We want anyone that’s doing animal research in the Arctic to consider participating in the archive, knowing that it will preserve the data for posterity, make it discoverable, allow people to collaborate with them, and make a larger picture.
See “Researchers DNA Barcode the Arctic”
Editor’s note: The interview was edited for brevity.


thescientist--2020-11-05--Denmark to Cull 17 Million Mink Amid SARS-CoV-2 Mutation Concerns

According to government officials in Denmark , mink raised on Danish farms carry a mutated version of the SARS-CoV-2 virus that is less sensitive to antibodies , which they say might thwart vaccine development .
Minks readily host and spread the virus and because this strain has now been found in humans , the prime minister announced on November 4 that Denmark would cull the entire stock of its mink farms , which equates to about 17 million animals spread across 1,000 farms .
So far , five human cases of this strain are linked to mink farms , and @ @ @ @ @ @ @ .
According to reports , the Danish government has shared its findings with the World Health Organization ( WHO ) and the European Centre for Disease Prevention and Control .
“ We have been informed by Denmark of a number of persons infected with coronavirus from mink , with some genetic changes in the virus , ” a representative from the WHO tells Reuters .
“ The Danish authorities are investigating the epidemiological and virological significance of these findings.
” The full genetic details of this strain and the serological findings of patients @ @ @ @ @ @ @ Someone would have to release the sequences soon , and the evolutionary biologists will be all over it , ” Jonathan Epstein , the vice president of science and outreach at EcoHealth Alliance who was not involved with the government report , tells The New York Times .
According to the prime minister , this strain makes it harder for the body to create antibodies against it , possibly undermining vaccines currently in development , although there is no evidence to show that is the case .
Denmark has had hundreds of COVID-19 @ @ @ @ @ @ @ pandemic , and the cull will now follow in the footsteps of similar efforts to reduce transmission through minks in Spain and the Netherlands .
As Denmark leads the world in mink production , it will have to kill 150 times as many animals as the other countries , which will likely crash the industry for years to come , according to The Guardian .
“ We have a great responsibility towards our own population , but with the mutation that has now been found , we have an even greater responsibility for @ @ @ @ @ @ @ , ” Danish Prime Minister Mette Frederiksen said at a news conference Wednesday , Reuters reports .
A letter published in Science on October 30 calls for the ban of what is described as “ unsustainable mink production ” in Denmark and other countries .
While the letter mainly focuses on COVID-19 outbreaks worldwide linked to mink farms , it also cites other zoonotic diseases that mink are known to harbor .
According to the BBC , ongoing studies are trying to determine why minks are such good hosts for SARS-CoV-2 .

ABOVE: © ISTOCK.COM, KONSTANTIN SOKOLOV
According to government officials in Denmark, mink raised on Danish farms carry a mutated version of the SARS-CoV-2 virus that is less sensitive to antibodies, which they say might thwart vaccine development. Minks readily host and spread the virus and because this strain has now been found in humans, the prime minister announced on November 4 that Denmark would cull the entire stock of its mink farms, which equates to about 17 million animals spread across 1,000 farms.
So far, five human cases of this strain are linked to mink farms, and 12 people have become infected in all. According to reports, the Danish government has shared its findings with the World Health Organization (WHO) and the European Centre for Disease Prevention and Control. “We have been informed by Denmark of a number of persons infected with coronavirus from mink, with some genetic changes in the virus,” a representative from the WHO tells Reuters. “The Danish authorities are investigating the epidemiological and virological significance of these findings.”
The full genetic details of this strain and the serological findings of patients have not been published yet.
“Someone would have to release the sequences soon, and the evolutionary biologists will be all over it,” Jonathan Epstein, the vice president of science and outreach at EcoHealth Alliance who was not involved with the government report, tells The New York Times.
According to the prime minister, this strain makes it harder for the body to create antibodies against it, possibly undermining vaccines currently in development, although there is no evidence to show that is the case.
Denmark has had hundreds of COVID-19 cases tied to mink farms throughout the pandemic, and the cull will now follow in the footsteps of similar efforts to reduce transmission through minks in Spain and the Netherlands. As Denmark leads the world in mink production, it will have to kill 150 times as many animals as the other countries, which will likely crash the industry for years to come, according to The Guardian.
“We have a great responsibility towards our own population, but with the mutation that has now been found, we have an even greater responsibility for the rest of the world as well,” Danish Prime Minister Mette Frederiksen said at a news conference Wednesday, Reuters reports.
A letter published in Science on October 30 calls for the ban of what is described as “unsustainable mink production” in Denmark and other countries. While the letter mainly focuses on COVID-19 outbreaks worldwide linked to mink farms, it also cites other zoonotic diseases that mink are known to harbor.
According to the BBC, ongoing studies are trying to determine why minks are such good hosts for SARS-CoV-2.


thescientist--2020-11-05--Scientists Probe Blockers for the Coronavirus Spike Protein

The pandemic coronavirus SARS-CoV-2 must break into our cells to set up an infection .
It gains entry using the now notorious spike protein but , typical of viruses , it must hijack our own biology to jimmy the lock .
Scientists are figuring out ways to intercept the virus before it can break in .
Viral spike proteins rely on protein-chomping enzymes , proteases , to re-shape them for cellular entry .
In the case of SARS-CoV-2 , the spike must first be snipped at a specific point by the furin protease before it latches onto a cell ’ @ @ @ @ @ @ @ protease must cut the spike protein and initiate viral fusion with the cell membrane .
The idea that researchers are pursuing is to block furin from cutting the spike .
Early on , before COVID-19 was officially declared a pandemic , scientists were already on the furin case , observing that the spike protein had amino acid sequences that looked worryingly like a furin docking site , with a motif of arginine-arginine-alanine-arginine .
Furin is a widespread enzyme in the body , potentially granting SARS-CoV-2 countless opportunities to infect cells .
SARS-CoV , @ @ @ @ @ @ @ earlier this century , does not have a furin cleavage site , but such sites are present in other dangerous pathogens such as HIV , Ebola , MERS-CoV , and avian influenza .
“ There are some highly pathogenic avian flu viruses , which occasionally infect people , and their spikes are cleaved by furins , so those viruses can reproduce in a number of different cells and tissues in the body , ” explains Vincent Racaniello , a virologist at Columbia University .
This separates them out from annual human influenza viruses @ @ @ @ @ @ @ furin , and may partly explain why those viruses are not as pathogenic as bird flus are .
If furin is critical to the pathogenicity of SARS-CoV-2 and its ability to enter different cell types , then blocking the protease might hinder viral replication .
To this end , researchers have been investigating whether furin is truly essential for SARS-CoV-2 infection and whether interfering with its activity lowers viral loads in cells .
In May , a group at the Germany Primate Centre led by Stefan Pöhlmann reported that initial cleavage of the @ @ @ @ @ @ @ protein is essential for SARS-CoV-2 entry into human lung cells and for the virus to fuse infected cells with other cells .
This fusion phenomenon , called syncytium , is driven by the so-called fusion peptide that is released by the spike as it is cleaved .
A French group reported that cells infected with SARS-CoV-2 are studded with spike proteins , which fuse with neighbors sporting ACE2 surface enzymes .
Fused cells have been seen in postmortem lung tissues of COVID-19 patients .
This cell-cell fusion has also been observed in tissues @ @ @ @ @ @ @ cause SARS and MERS .
Syncytium allows virus-infected cells join other cells , creating contiguous viral factories of 10 to 20 cells .
The strategy enables the virus to hijack new cells without exiting into the body , thus eluding immune surveillance .
The French group concluded that cell-cell fusion is a feature of severe COVID-19 and is facilitated by TMPRSS2 , another protease involved in snipping the spike protein .
Another German group reported in July evidence backing TMPRSS2 ’ s importance in infection and that SARS-CoV-2 replication was strongly inhibited by @ @ @ @ @ @ @ in human airway cells .
In a preprint posted to bioRxiv in August , Vineet Menachery of the University of Texas Medical Branch and his colleagues reported that deletion of the spike protein ’ s furin cleavage site from SARS-CoV-2 ramped up replication in a monkey cell line , but attenuated replication in respiratory cells and pathogenesis in vivo in hamsters .
“ My expectation would be that the same holds true for SARS-CoV-2 in infected human patients , ” Pöhlmann says of the hamster result .
As for the conflicting data from @ @ @ @ @ @ @ still looking for answers .
The search for a drug to block furin The hunt for furin inhibitors to use clinically is well underway .
Scientists in Taiwan tested four inhibitors of furin and other similar proteases in human cells infected with SARS-CoV-2 .
Cleavage and cell-cell fusion were abolished in those cells treated with the furin inhibitors CMK ( decanoyl-RVKR-chloromethylketone ) and naphthofluorescein , the authors reported in September in Cell .
CMK is a peptide inhibitor long used as a research tool that competes with furin for SARS-CoV-2 ’ s attention @ @ @ @ @ @ @ used in research , is a small molecule inhibitor of furin ’ s activity .
“ These two inhibitors decrease not only syncytium , but also viral production , ” says senior author Shiou-Hwei Yeh of National Taiwan University Hospital .
“ Our study confirms the critical role of furin cleavage for fusion activity of the spike protein , but we also identified two antiviral lead compounds for drug development.
” Yeh has developed a number of derivatives of naphthofluorescein to increase its selectivity for furin .
She now plans to test her @ @ @ @ @ @ @ ACE2 .
Gonzalo Izaguirre , a biochemist at the University of Illinois at Chicago , has studied natural furin inhibitors called serpins for many years .
He is now working on an engineered serpin-type furin inhibitor that can block cell entry by a synthetic , noninfectious virus fitted with the SARS-CoV-2 spike .
“ If effective , ” he notes by email , “ this inhibitor could be the basis of a potential therapy to treat COVID-19.
” There are already protease-inhibiting drugs approved for unrelated conditions that seem to affect furin , @ @ @ @ @ @ @ University in Utah says would be worth investigating for possible repurposing to treat COVID-19 .
For instance , nelfinavir is a drug approved to treat HIV that Watt says affects furin .
In an unrelated study on anemia , “ we found that an HIV protease inhibitor could bind furin and inhibits its action , ” explains Watt .
The drug tightly binds to the catalytic site of furin and also to other proteases that act on SARS-CoV-2 , computational studies from his group and others show , says Watt .
Also , @ @ @ @ @ @ @ seem to act against SARS-CoV-2 , by binding to its main protease .
Yet another strategy could be to combine a furin blocker with a second protease inhibitor , such as for TMPRSS2 .
In a July preprint , Pöhlmann and colleagues concluded that TMPRSS2 was essential for SARS-CoV-2 to infect human airway cells , and suggested combining a TMPRSS2 and a furin inhibitor as an antiviral strategy .
“ Furin is an essential enzyme in the human body .
You can not live without furin , ” says Pöhlmann .
“ TMPRSS2 @ @ @ @ @ @ @ mice , which can live happily without it.
” The combination of two inhibitors could allow for a lower dose of a furin blocker , or a faster one-two punch , thereby necessitating only a brief inhibition of furin .
“ You would want inhibitors of both furin and TMPRSS2 , ” agrees Watt .
He suggests this may be feasible using nelfinavir in combination with camostat mesilate , a TMPRSS2 blocker approved in Japan for the treatment of pancreatitis and which Pöhlmann had reported can inhibit SARS-CoV-2 activation .
There are a @ @ @ @ @ @ @ conditions unrelated to coronaviruses .
Moreover , a Danish trial is currently testing the effect of camostat in COVID-19 patients .
Repurposing approved drugs to block proteases essential for the virus would allow for faster clinical trials to test their efficacy against SARS-CoV-2 and perhaps benefit COVID-19 patients through new , much needed antiviral therapies .
Watt would like to trial nelfinavir in COVID-19 patients , but has yet to find a clinical collaborator or funding .
The limitations of interfering with furin Not everyone is convinced that blocking furin will work .
@ @ @ @ @ @ @ a preprint in August that crippling the gene for furin in a human embryonic cell line diminishes , but does not altogether stop , replication of SARS-CoV-2 .
“ We found that deleting the gene for furin slowed cell-cell fusion but did not prevent it , ” immunologist Leo James of the University of Cambridge explains by email .
“ The fact that the S protein was still cleaved in furin knockout cells suggest that there may be other proteases that can take its place , albeit less efficiently , ” he adds @ @ @ @ @ @ @ these results are bad news for generating antivirals that block furin .
“ Even if a compound achieves 100 % inhibition it will not completely prevent infection , ” James says .
A June study in iScience similarly suggested that enzymes related to furin could also cut the spike protein .
Still , that need not be the last word .
“ I would say that they haven ’ t used the right cells , ” counters Racaniello .
Cell lines from monkeys and human embryo cells can tap different proteases to do @ @ @ @ @ @ @ adds , setting them apart from human lung cells .
Furthermore , Racaniello and others say it may not be necessary to entirely lock SARS-CoV-2 out of cells .
“ Clearly , if you take away this cleavage site the virus can still reproduce to a certain extent , ” says Racaniello .
“ It could be that a ten- or one-hundred-fold reduction in virus output is enough to prevent infection , and you can not tell that from a cell line .
You need to look in an animal model.
” A @ @ @ @ @ @ @ essential roles in our cell , ” says Racaniello , so if you block the enzyme , “ you will have toxicity associated with that.
” Plenty of drugs have been developed with the aim of inhibiting furin , but none have made it through to patients .
“ Furin inhibitors are quite toxic , ” confirms Izaguirre .
This does not rule them out .
Inhibitors could perhaps be delivered for a short period of time to knock down viral load at a critical juncture .
“ It might be possible that @ @ @ @ @ @ @ very short amount of time , to limited unwanted side effects , ” agrees Pöhlmann .
Although nelfinavir is approved by the US Food and Drug Administration ( FDA ) for treating HIV , it has not yet been approved as a furin inhibitor .
Watt is currently seeking FDA approval for nelfinavir as a furin inhibitor to treat anemia caused by chronic inflammation in hopes that future studies will allow the drug to be approved as a furin inhibitor for other indications such as SARS-CoV-2 infections .

ABOVE: © ISTOCK.COM, DESIGN CELLS
The pandemic coronavirus SARS-CoV-2 must break into our cells to set up an infection. It gains entry using the now notorious spike protein but, typical of viruses, it must hijack our own biology to jimmy the lock. Scientists are figuring out ways to intercept the virus before it can break in.
Viral spike proteins rely on protein-chomping enzymes, proteases, to re-shape them for cellular entry. In the case of SARS-CoV-2, the spike must first be snipped at a specific point by the furin protease before it latches onto a cell’s ACE2 receptor. Then, another protease must cut the spike protein and initiate viral fusion with the cell membrane.
The idea that researchers are pursuing is to block furin from cutting the spike.
Early on, before COVID-19 was officially declared a pandemic, scientists were already on the furin case, observing that the spike protein had amino acid sequences that looked worryingly like a furin docking site, with a motif of arginine-arginine-alanine-arginine. Furin is a widespread enzyme in the body, potentially granting SARS-CoV-2 countless opportunities to infect cells. SARS-CoV, the coronavirus responsible for the SARS outbreak earlier this century, does not have a furin cleavage site, but such sites are present in other dangerous pathogens such as HIV, Ebola, MERS-CoV, and avian influenza.
The hunt for furin inhibitors to use clinically is well underway.
“There are some highly pathogenic avian flu viruses, which occasionally infect people, and their spikes are cleaved by furins, so those viruses can reproduce in a number of different cells and tissues in the body,” explains Vincent Racaniello, a virologist at Columbia University. This separates them out from annual human influenza viruses, whose spikes are not cleaved by furin, and may partly explain why those viruses are not as pathogenic as bird flus are.
If furin is critical to the pathogenicity of SARS-CoV-2 and its ability to enter different cell types, then blocking the protease might hinder viral replication. To this end, researchers have been investigating whether furin is truly essential for SARS-CoV-2 infection and whether interfering with its activity lowers viral loads in cells.
Furin as SARS-CoV-2’s partner in crime
In May, a group at the Germany Primate Centre led by Stefan Pöhlmann reported that initial cleavage of the S1 and S2 subunits of the spike protein is essential for SARS-CoV-2 entry into human lung cells and for the virus to fuse infected cells with other cells. This fusion phenomenon, called syncytium, is driven by the so-called fusion peptide that is released by the spike as it is cleaved.
A French group reported that cells infected with SARS-CoV-2 are studded with spike proteins, which fuse with neighbors sporting ACE2 surface enzymes. Fused cells have been seen in postmortem lung tissues of COVID-19 patients. This cell-cell fusion has also been observed in tissues from people infected with the coronaviruses that cause SARS and MERS.
Syncytium allows virus-infected cells join other cells, creating contiguous viral factories of 10 to 20 cells. The strategy enables the virus to hijack new cells without exiting into the body, thus eluding immune surveillance. The French group concluded that cell-cell fusion is a feature of severe COVID-19 and is facilitated by TMPRSS2, another protease involved in snipping the spike protein.
Another German group reported in July evidence backing TMPRSS2’s importance in infection and that SARS-CoV-2 replication was strongly inhibited by a synthetic furin inhibitor, MI-1851, in human airway cells.
In a preprint posted to bioRxiv in August, Vineet Menachery of the University of Texas Medical Branch and his colleagues reported that deletion of the spike protein’s furin cleavage site from SARS-CoV-2 ramped up replication in a monkey cell line, but attenuated replication in respiratory cells and pathogenesis in vivo in hamsters.
“My expectation would be that the same holds true for SARS-CoV-2 in infected human patients,” Pöhlmann says of the hamster result. As for the conflicting data from the monkey cells, the researchers are still looking for answers.
The search for a drug to block furin
The hunt for furin inhibitors to use clinically is well underway. Scientists in Taiwan tested four inhibitors of furin and other similar proteases in human cells infected with SARS-CoV-2. Cleavage and cell-cell fusion were abolished in those cells treated with the furin inhibitors CMK (decanoyl-RVKR-chloromethylketone) and naphthofluorescein, the authors reported in September in Cell. CMK is a peptide inhibitor long used as a research tool that competes with furin for SARS-CoV-2’s attention, while naphthofluorescein, a newer compound used in research, is a small molecule inhibitor of furin’s activity.
“These two inhibitors decrease not only syncytium, but also viral production,” says senior author Shiou-Hwei Yeh of National Taiwan University Hospital. “Our study confirms the critical role of furin cleavage for fusion activity of the spike protein, but we also identified two antiviral lead compounds for drug development.”
Yeh has developed a number of derivatives of naphthofluorescein to increase its selectivity for furin. She now plans to test her derivatives in mouse models that express human ACE2.
Gonzalo Izaguirre, a biochemist at the University of Illinois at Chicago, has studied natural furin inhibitors called serpins for many years. He is now working on an engineered serpin-type furin inhibitor that can block cell entry by a synthetic, noninfectious virus fitted with the SARS-CoV-2 spike. “If effective,” he notes by email, “this inhibitor could be the basis of a potential therapy to treat COVID-19.”
There are already protease-inhibiting drugs approved for unrelated conditions that seem to affect furin, which biochemist Richard Watt of Brigham Young University in Utah says would be worth investigating for possible repurposing to treat COVID-19. For instance, nelfinavir is a drug approved to treat HIV that Watt says affects furin. In an unrelated study on anemia, “we found that an HIV protease inhibitor could bind furin and inhibits its action,” explains Watt.
Plenty of drugs have been developed with the aim of inhibiting furin, but none have made it through to patients.
The drug tightly binds to the catalytic site of furin and also to other proteases that act on SARS-CoV-2, computational studies from his group and others show, says Watt. Also, an earlier preprint noted that nelfinavir does seem to act against SARS-CoV-2, by binding to its main protease.
Yet another strategy could be to combine a furin blocker with a second protease inhibitor, such as for TMPRSS2. In a July preprint, Pöhlmann and colleagues concluded that TMPRSS2 was essential for SARS-CoV-2 to infect human airway cells, and suggested combining a TMPRSS2 and a furin inhibitor as an antiviral strategy.
“Furin is an essential enzyme in the human body. You cannot live without furin,” says Pöhlmann. “TMPRSS2 is not essential, at least in mice, which can live happily without it.” The combination of two inhibitors could allow for a lower dose of a furin blocker, or a faster one-two punch, thereby necessitating only a brief inhibition of furin.
“You would want inhibitors of both furin and TMPRSS2,” agrees Watt. He suggests this may be feasible using nelfinavir in combination with camostat mesilate, a TMPRSS2 blocker approved in Japan for the treatment of pancreatitis and which Pöhlmann had reported can inhibit SARS-CoV-2 activation. There are a number of approved inhibitors of TMPRSS2 for conditions unrelated to coronaviruses. Moreover, a Danish trial is currently testing the effect of camostat in COVID-19 patients.
Repurposing approved drugs to block proteases essential for the virus would allow for faster clinical trials to test their efficacy against SARS-CoV-2 and perhaps benefit COVID-19 patients through new, much needed antiviral therapies. Watt would like to trial nelfinavir in COVID-19 patients, but has yet to find a clinical collaborator or funding.
The limitations of interfering with furin
Not everyone is convinced that blocking furin will work. A group in the UK reported in a preprint in August that crippling the gene for furin in a human embryonic cell line diminishes, but does not altogether stop, replication of SARS-CoV-2. “We found that deleting the gene for furin slowed cell-cell fusion but did not prevent it,” immunologist Leo James of the University of Cambridge explains by email.
“The fact that the S protein was still cleaved in furin knockout cells suggest that there may be other proteases that can take its place, albeit less efficiently,” he adds. On the face of it, these results are bad news for generating antivirals that block furin. “Even if a compound achieves 100% inhibition it will not completely prevent infection,” James says. A June study in iScience similarly suggested that enzymes related to furin could also cut the spike protein.
Still, that need not be the last word. “I would say that they haven’t used the right cells,” counters Racaniello. Cell lines from monkeys and human embryo cells can tap different proteases to do the same job as furin, he adds, setting them apart from human lung cells.
Furthermore, Racaniello and others say it may not be necessary to entirely lock SARS-CoV-2 out of cells. “Clearly, if you take away this cleavage site the virus can still reproduce to a certain extent,” says Racaniello. “It could be that a ten- or one-hundred-fold reduction in virus output is enough to prevent infection, and you cannot tell that from a cell line. You need to look in an animal model.”
A separate problem “is that furin has essential roles in our cell,” says Racaniello, so if you block the enzyme, “you will have toxicity associated with that.” Plenty of drugs have been developed with the aim of inhibiting furin, but none have made it through to patients. “Furin inhibitors are quite toxic,” confirms Izaguirre.
This does not rule them out. Inhibitors could perhaps be delivered for a short period of time to knock down viral load at a critical juncture. “It might be possible that furin inhibitors are only applied for a very short amount of time, to limited unwanted side effects,” agrees Pöhlmann.
Although nelfinavir is approved by the US Food and Drug Administration (FDA) for treating HIV, it has not yet been approved as a furin inhibitor. Watt is currently seeking FDA approval for nelfinavir as a furin inhibitor to treat anemia caused by chronic inflammation in hopes that future studies will allow the drug to be approved as a furin inhibitor for other indications such as SARS-CoV-2 infections.


thescientist--2020-11-06--Regulators of Gene Activity in Animals Are Deeply Conserved

ABOVE : Researchers used a fluorescing protein to explore cell-specific gene expression patterns in zebrafish containing a sponge-derived enhancer .
DAVID ZHENG | VICTOR CHANG CARDIAC RESEARCH INSTITUTE The functionality of genetic regulatory elements known as enhancers is widely conserved among species of animals spread across the evolutionary tree .
When researchers inserted an enhancer sequence from a sponge into zebrafish and mice , both vertebrates were able to interpret the genetic information and drive cell-specific expression of a developmental gene , even within cell types that a sponge doesn ’ t have .
The results of the new study @ @ @ @ @ @ @ show that , at least in some cases , enhancer function persists across species that last shared a common ancestor as far back as 700 million years ago .
Once bound by proteins , enhancers control where , when , and how genes are regulated , and are largely responsible for cell differentiation during development .
“ The reason why a muscle cell is different from a skin cell is all due to how genes are regulated .
That ’ s why it ’ s really important to understand these regions , ” @ @ @ @ @ @ @ at the Victor Chang Cardiac Research Institute in Australia and the lead author of the new study , tells The Scientist .
“ Our discovery is exciting because we know that these regions evolve really rapidly , making them more difficult to find.
” Many enhancers lie in noncoding regions of the genome , portions Wong refers to as “ dark matter ” because most genomic research focuses on exons , which code for proteins .
But growing evidence suggests the human genome may have hundreds of thousands of enhancers , far outpacing @ @ @ @ @ @ @ Enhancers also evolve rapidly compared to the transcription factors they interact with and the genes they regulate , meaning that enhancers may not retain their sequence fidelity over time .
The conventional method of comparing genomes by aligning them and looking for similar sequences is therefore ineffective for enhancers , whose motifs of short DNA repeats can change so much that they are no longer recognizable .
Indeed , not a single enhancer has been shown to be conserved across the entire animal kingdom .
Wong and her colleagues suspected , though , @ @ @ @ @ @ @ “ regulatory grammar , ” meaning they can retain their function even when the number , arrangement , or type of motifs that make up the enhancer are shuffled .
If this were true , enhancers could , in theory , maintain their function across different species .
To test this hypothesis , the team went looking for putative enhancers in the sponge Amphimedon queenslandica , an Australian species frequently used to study the evolution of metazoans .
They targeted microsyntenic gene pairs , in which one gene ( the target ) is @ @ @ @ @ @ @ ( the bystander ) .
Because the target gene is often critical to proper development , the researchers reasoned that selection would keep the genes more stable over time .
Although they identified 60 such gene pairs , the researchers focused most heavily on a single pair with a known regulatory role , Islet-Scaper , in which the Islet gene is the target and the Scaper gene is the bystander .
The enhancer , called eISL , is located on the intron of Scaper .
In vertebrates , Islet is involved in nervous @ @ @ @ @ @ @ functions .
The team first inserted the entire Islet-Scaper pair into a transgenic zebrafish embryo that still contained its own Islet genes ( zebrafish have three paralogues ) and enhancers .
If the fish ’ s regulatory machinery had lost the ability to recognize binding sites on the sponge enhancer , researchers would not have seen any expression of the sponge Islet gene .
However , Wong and her colleagues detected transcripts of sponge Islet in addition to the fish ’ s own versions , meaning that the zebrafish ’ s transcription factors @ @ @ @ @ @ @ ’ s binding sites even after hundreds of millions of years of evolution .
Next , they inserted the sponge enhancer upstream of a green fluorescent protein that caused the fish to glow in specific cell types where the enhancer was active .
Even though sponges lack brains , eyes , and hearts , the fish showed cell-specific expression patterns consistent with a wildtype zebrafish , findings that were supported by a subsequent experiment using mice .
Sponge-derived enhancer activity caused the fish to glow most brightly in their nervous systems , ears @ @ @ @ @ @ @ also showed expression in their eyes.there is a functional conservation even though the sequence itself .
.
.
is not recognized . ''
“ When we put these sequences into completely different animals that are very divergent , we see that it ’ s able to drive cell-type specific expression , ” Wong says , findings which suggest that “ there is a functional conservation even though the sequence itself .
.
.
is not recognized.
” While the team is not the first to confirm that sequences need not look alike to @ @ @ @ @ @ @ de Souza , a developmental biologist at the University of Buenos Aires who has worked with enhancers and Islet and was not involved in the current research , was surprised at just how deep this conservation ran .
“ We are dealing with a sponge , the most extreme phylogenetic distance that you can get in the animal kingdom , ” de Souza tells The Scientist .
“ I think this is pointing to a more general phenomenon.
” Having shown that eISL is functionally conserved , Wong next developed a computational tool @ @ @ @ @ @ @ various databases based on characteristics of the enhancers ’ binding motifs—their number , location , and sequence type , rather than the entire sequences themselves—to find enhancer orthologs in sponges , zebrafish , mice , and humans .
When they created transgenic fish with their suspected eISL human and mouse enhancer candidates , they found similar cell-specific Islet expression patterns to what they had seen in their earlier experiments using the sponge version .
“ It is clear , and this study reinforces it , that it does not require that you keep @ @ @ @ @ @ @ , in the same number , in the same orientation , ” Michael Eisen , a molecular biologist at the University of California , Berkeley , who was not part of the current study , tells The Scientist .
“ You can accomplish the same input-output pattern in different ways . ''
De Souza says he would like to know more about what the Islet enhancer is doing in the sponge itself .
While the paper has proven that the section of DNA can function as an enhancer , performing these transgenic experiments @ @ @ @ @ @ @ genomic context , ” de Souza says .
A better understanding of its role in A. queenslandica would require genomic manipulations such as gene knockout experiments that are common in model organisms , but may be difficult in more exotic species .
Eisen says he wants to see the same rigor the team brought to the Islet-Scaper pair applied to hundreds , if not thousands , of additional putative enhancers across species .
With so little known about enhancers more generally , it ’ s hard to say whether the team ’ s @ @ @ @ @ @ @ these regulatory elements remain conserved over time .
“ I still think people don ’ t have an appreciation for just how weird the evolution of enhancers is , ” Eisen says .
“ It ’ s good for people to be reminded with new examples periodically , because I think that the phenomenon that this paper describes is still not widely appreciated , even by people in the transcription field .
”

ABOVE: Researchers used a fluorescing protein to explore cell-specific gene expression patterns in zebrafish containing a sponge-derived enhancer.
DAVID ZHENG | VICTOR CHANG CARDIAC RESEARCH INSTITUTE
The functionality of genetic regulatory elements known as enhancers is widely conserved among species of animals spread across the evolutionary tree. When researchers inserted an enhancer sequence from a sponge into zebrafish and mice, both vertebrates were able to interpret the genetic information and drive cell-specific expression of a developmental gene, even within cell types that a sponge doesn’t have.
The results of the new study, published November 5 in Science, show that, at least in some cases, enhancer function persists across species that last shared a common ancestor as far back as 700 million years ago.
Once bound by proteins, enhancers control where, when, and how genes are regulated, and are largely responsible for cell differentiation during development. “The reason why a muscle cell is different from a skin cell is all due to how genes are regulated. That’s why it’s really important to understand these regions,” Emily Wong, a computational genomics researcher at the Victor Chang Cardiac Research Institute in Australia and the lead author of the new study, tells The Scientist. “Our discovery is exciting because we know that these regions evolve really rapidly, making them more difficult to find.”
Amphimedon queenslandica was the first sponge to have its genome sequenced, and has since been used to study development and the evolution of complexity in metazoans. University of queensland
Many enhancers lie in noncoding regions of the genome, portions Wong refers to as “dark matter” because most genomic research focuses on exons, which code for proteins. But growing evidence suggests the human genome may have hundreds of thousands of enhancers, far outpacing our roughly 20,000 protein coding genes. Enhancers also evolve rapidly compared to the transcription factors they interact with and the genes they regulate, meaning that enhancers may not retain their sequence fidelity over time.
The conventional method of comparing genomes by aligning them and looking for similar sequences is therefore ineffective for enhancers, whose motifs of short DNA repeats can change so much that they are no longer recognizable. Indeed, not a single enhancer has been shown to be conserved across the entire animal kingdom.
Wong and her colleagues suspected, though, that enhancers may be flexible in their “regulatory grammar,” meaning they can retain their function even when the number, arrangement, or type of motifs that make up the enhancer are shuffled. If this were true, enhancers could, in theory, maintain their function across different species.
To test this hypothesis, the team went looking for putative enhancers in the sponge Amphimedon queenslandica, an Australian species frequently used to study the evolution of metazoans. They targeted microsyntenic gene pairs, in which one gene (the target) is regulated by an enhancer within another gene (the bystander). Because the target gene is often critical to proper development, the researchers reasoned that selection would keep the genes more stable over time.
Although they identified 60 such gene pairs, the researchers focused most heavily on a single pair with a known regulatory role, Islet-Scaper, in which the Islet gene is the target and the Scaper gene is the bystander. The enhancer, called eISL, is located on the intron of Scaper. In vertebrates, Islet is involved in nervous system and heart development, among other functions.
The team first inserted the entire Islet-Scaper pair into a transgenic zebrafish embryo that still contained its own Islet genes (zebrafish have three paralogues) and enhancers. If the fish’s regulatory machinery had lost the ability to recognize binding sites on the sponge enhancer, researchers would not have seen any expression of the sponge Islet gene. However, Wong and her colleagues detected transcripts of sponge Islet in addition to the fish’s own versions, meaning that the zebrafish’s transcription factors were still able to read the sponge’s binding sites even after hundreds of millions of years of evolution.
Next, they inserted the sponge enhancer upstream of a green fluorescent protein that caused the fish to glow in specific cell types where the enhancer was active. Even though sponges lack brains, eyes, and hearts, the fish showed cell-specific expression patterns consistent with a wildtype zebrafish, findings that were supported by a subsequent experiment using mice. Sponge-derived enhancer activity caused the fish to glow most brightly in their nervous systems, ears, and skin, while the mice also showed expression in their eyes.there is a functional conservation even though the sequence itself . . . is not recognized."
“When we put these sequences into completely different animals that are very divergent, we see that it’s able to drive cell-type specific expression,” Wong says, findings which suggest that “there is a functional conservation even though the sequence itself . . . is not recognized.”
While the team is not the first to confirm that sequences need not look alike to translate between animals, Flávio S. J. de Souza, a developmental biologist at the University of Buenos Aires who has worked with enhancers and Islet and was not involved in the current research, was surprised at just how deep this conservation ran. “We are dealing with a sponge, the most extreme phylogenetic distance that you can get in the animal kingdom,” de Souza tells The Scientist. “I think this is pointing to a more general phenomenon.”
There is a functional conservation even though the sequence itself . . . is not recognized. —Emily Wong, Victor Chang Cardiac Research Institute
Having shown that eISL is functionally conserved, Wong next developed a computational tool to scan microsyntenic regions of genomes from various databases based on characteristics of the enhancers’ binding motifs—their number, location, and sequence type, rather than the entire sequences themselves—to find enhancer orthologs in sponges, zebrafish, mice, and humans. When they created transgenic fish with their suspected eISL human and mouse enhancer candidates, they found similar cell-specific Islet expression patterns to what they had seen in their earlier experiments using the sponge version.
“It is clear, and this study reinforces it, that it does not require that you keep the binding sites in the same place, in the same number, in the same orientation,” Michael Eisen, a molecular biologist at the University of California, Berkeley, who was not part of the current study, tells The Scientist. “You can accomplish the same input-output pattern in different ways."
De Souza says he would like to know more about what the Islet enhancer is doing in the sponge itself. While the paper has proven that the section of DNA can function as an enhancer, performing these transgenic experiments “takes it outside of its native genomic context,” de Souza says. A better understanding of its role in A. queenslandica would require genomic manipulations such as gene knockout experiments that are common in model organisms, but may be difficult in more exotic species.
Eisen says he wants to see the same rigor the team brought to the Islet-Scaper pair applied to hundreds, if not thousands, of additional putative enhancers across species. With so little known about enhancers more generally, it’s hard to say whether the team’s findings touch on an outlier in how these regulatory elements remain conserved over time.
“I still think people don’t have an appreciation for just how weird the evolution of enhancers is,” Eisen says. “It’s good for people to be reminded with new examples periodically, because I think that the phenomenon that this paper describes is still not widely appreciated, even by people in the transcription field.”


thescientist--2020-11-06--Alcohol, Bowel Movements May Confound Microbiology Studies

Gut microbes represent a complex ecology of tens of trillions of bacterial cells that have far-reaching effects—from mental health disorders to cardiovascular health .
While the composition of the microbiome has been correlated with certain diseases such as Parkinson ’ s disease , it is hard to unpack whether such associations are just correlation , a consequence of the health condition , or a cause or contribution of the illness .
A review published in Nature on November 4 aims to search for potentially confounding variables by analyzing physiological and lifestyle differences between people with and without a particular disease @ @ @ @ @ @ @ with the composition of the gut microbiota .
The Scientist spoke with National Institute of Allergy and Infectious Diseases immunologist Ivan Vujkovic-Cvijin , a postdoc and coauthor of the review , about its findings .
The Scientist : What motivated you to write this paper ?
Ivan Vujkovic-Cvijin : I ’ ve been involved in the field of examining how the gut microbiome may impact the health of people with HIV .
In that field , there was a fascinating discovery that men who have sex with men have a very different gut @ @ @ @ @ @ @ with women .
The predominant population of people with HIV in the United States and a lot of Western Europe are men who have sex with men .
It turned out that when we looked at some of the studies that that had been done in the field , we were comparing people with HIV that are men who have sex with men to uninfected subjects that were men who have sex with women .
In those studies , we weren ’ t only finding differences that were dependent on HIV , but @ @ @ @ @ @ @ we were really intending only to identify those bacteria that differ as a result of HIV .
In that sense , we can say that those studies were confounded by sexual preference .
It turns out that while HIV does have an impact on the gut microbiome , this other factor that we hadn ’ t expected has a much stronger effect on the microbiome .
That really led us to take a step back and ask what other confounding variables there might be out there that we are totally unaware of .
@ @ @ @ @ @ @ examination of what variables might be confounding the comparisons of disease subjects to undiseased subjects , so that really spurred this this investigation .
TS : What other confounding variables did you find that were surprising ?
IVC : There were some things that had been relatively well described in the literature as having a major impact on the microbiome and had already been started to be incorporated in study designs , such as age and sex .
But we were surprised to find that alcohol consumption and bowel movement quality—by that I @ @ @ @ @ @ @ , hard , or normal—were pretty strong sources of confounding effects for many diseases .
This is something that I wouldn ’ t say was appreciated by the field and it was certainly an unexpected result .
Both of those factors seemed to have a really strong impact on the microbiome and , importantly , those two variables often differ in people with a disease compared to people without a disease .
Our alcohol consumption changes what when we learn of a diagnosis .
[ For example , ] we ’ re taking @ @ @ @ @ @ @ alcohol use and sometimes the other way as well .
And bowel movement quality is often affected by certain diseases .
We hope that future studies incorporate consideration of those [ two factors ] .
We are all very unique in terms of our immune systems , how we respond to infectious disease , and how susceptible we are to other chronic diseases .
Biology , in a lot of ways , is an attempt to understand what causes these differences in how people respond .
Certainly , we know that the microbiome @ @ @ @ @ @ @ estimates say that I only share about ten percent of the bacteria that you might have at a certain taxonomic classification .
We ’ re excited that we may be expanding our understanding of the determinants of why my microbiome may be different from yours .
TS : Can you give me a breakdown of your findings with alcohol consumption ?
IVC : We did see a very dose-dependent effect .
The more an individual consumed alcohol , the greater the impact on the microbiome .
Even occasional drinking—one to two times per @ @ @ @ @ @ @ microbiome .
One thing that we thought was interesting is that alcohol itself is used as a disinfectant in our microbiology labs , and one might expect for alcohol to kill some bacteria in the gut and reduce diversity of the gut microbiome , but we actually found the opposite effect , which we find fascinating .
There was an increase in diversity that was also dose-dependent .
We don ’ t know the implications on health of this increased diversity quite yet , but we are intrigued by the finding because it @ @ @ @ @ @ @ Tell me a bit about your methodology .
IVC : Oh man , it ’ s really beautiful .
We were super stoked about the contribution of data science to our field of the microbiome .
So what we did was we took advantage of an enormous study—the largest publicly available dataset examining gut microbiomes in human events across the world—and along with these samples , there were questionnaires given to every individual that were very detailed—over a hundred questions .
We had a lot of information about each sample that we were @ @ @ @ @ @ @ that had the greatest impact on the microbiome .
The methodology we chose to use was machine learning , and a really beautiful component of machine learning is the concept of cross-validation where you take a portion of your study participants that differ in one variable—let ’ s say old individuals versus young—you take a subset of the total that you ’ re comparing and you examine what patterns in the microbiome distinguish those two groups .
With the subjects that the algorithm didn ’ t see , you test whether the patterns @ @ @ @ @ @ @ are robust and are also observed in the unseen subjects .
This is a very powerful way to assess how strong and replicable the impact on the microbiome is of a given variable .
We could quantify that discreetly , and we did so for all of the variables in the dataset and we ranked them by importance .
TS : What recommendations do you have for microbiologists or folks reading about microbiology ?
IVC : Based on these findings , we put forth the recommendation for human microbiome studies to capture information @ @ @ @ @ @ @ things that were not typically collected as part of clinical studies , whereas age , BMI , and sex more typically are .
We recommend an expansion of the variables that are collected into terms of information and if possible to match these variables between the groups that are being compared , because they have an impact on the microbiome , and we want to mitigate how much studies are actually looking at these effects of these confounding variables and instead narrow down their results to what ’ s really of interest in @ @ @ @ @ @ @ studied .

ABOVE: © ISTOCK.COM,
DRAZEN ZIGIC
Gut microbes represent a complex ecology of tens of trillions of bacterial cells that have far-reaching effects—from mental health disorders to cardiovascular health. While the composition of the microbiome has been correlated with certain diseases such as Parkinson’s disease, it is hard to unpack whether such associations are just correlation, a consequence of the health condition, or a cause or contribution of the illness.
A review published in Nature on November 4 aims to search for potentially confounding variables by analyzing physiological and lifestyle differences between people with and without a particular disease and identifying differences that might be associated with the composition of the gut microbiota.
The Scientist spoke with National Institute of Allergy and Infectious Diseases immunologist Ivan Vujkovic-Cvijin, a postdoc and coauthor of the review, about its findings.
The Scientist: What motivated you to write this paper?
Ivan Vujkovic-Cvijin: I’ve been involved in the field of examining how the gut microbiome may impact the health of people with HIV. In that field, there was a fascinating discovery that men who have sex with men have a very different gut microbiome composition than men who have sex with women. The predominant population of people with HIV in the United States and a lot of Western Europe are men who have sex with men. It turned out that when we looked at some of the studies that that had been done in the field, we were comparing people with HIV that are men who have sex with men to uninfected subjects that were men who have sex with women. In those studies, we weren’t only finding differences that were dependent on HIV, but also depending on sexual preference, when we were really intending only to identify those bacteria that differ as a result of HIV.
Ivan Vujkovic-Cvijin NIAID
In that sense, we can say that those studies were confounded by sexual preference. It turns out that while HIV does have an impact on the gut microbiome, this other factor that we hadn’t expected has a much stronger effect on the microbiome. That really led us to take a step back and ask what other confounding variables there might be out there that we are totally unaware of. There hadn’t been an exhaustive examination of what variables might be confounding the comparisons of disease subjects to undiseased subjects, so that really spurred this this investigation.
TS: What other confounding variables did you find that were surprising?
IVC: There were some things that had been relatively well described in the literature as having a major impact on the microbiome and had already been started to be incorporated in study designs, such as age and sex. But we were surprised to find that alcohol consumption and bowel movement quality—by that I mean whether the stool is typically loose, hard, or normal—were pretty strong sources of confounding effects for many diseases. This is something that I wouldn’t say was appreciated by the field and it was certainly an unexpected result.
Both of those factors seemed to have a really strong impact on the microbiome and, importantly, those two variables often differ in people with a disease compared to people without a disease. Our alcohol consumption changes what when we learn of a diagnosis. [For example,] we’re taking medications [that often] limit our alcohol use and sometimes the other way as well. And bowel movement quality is often affected by certain diseases. We hope that future studies incorporate consideration of those [two factors].
We are all very unique in terms of our immune systems, how we respond to infectious disease, and how susceptible we are to other chronic diseases. Biology, in a lot of ways, is an attempt to understand what causes these differences in how people respond. Certainly, we know that the microbiome is very different across populations. Some estimates say that I only share about ten percent of the bacteria that you might have at a certain taxonomic classification. We’re excited that we may be expanding our understanding of the determinants of why my microbiome may be different from yours.
TS: Can you give me a breakdown of your findings with alcohol consumption?
IVC: We did see a very dose-dependent effect. The more an individual consumed alcohol, the greater the impact on the microbiome. Even occasional drinking—one to two times per week—did have a measurable impact on the microbiome. One thing that we thought was interesting is that alcohol itself is used as a disinfectant in our microbiology labs, and one might expect for alcohol to kill some bacteria in the gut and reduce diversity of the gut microbiome, but we actually found the opposite effect, which we find fascinating. There was an increase in diversity that was also dose-dependent. We don’t know the implications on health of this increased diversity quite yet, but we are intrigued by the finding because it was a relative surprise.
TS: Tell me a bit about your methodology.
IVC: Oh man, it’s really beautiful. We were super stoked about the contribution of data science to our field of the microbiome. So what we did was we took advantage of an enormous study—the largest publicly available dataset examining gut microbiomes in human events across the world—and along with these samples, there were questionnaires given to every individual that were very detailed—over a hundred questions. We had a lot of information about each sample that we were able to use to identify the variables that had the greatest impact on the microbiome.
The methodology we chose to use was machine learning, and a really beautiful component of machine learning is the concept of cross-validation where you take a portion of your study participants that differ in one variable—let’s say old individuals versus young—you take a subset of the total that you’re comparing and you examine what patterns in the microbiome distinguish those two groups. With the subjects that the algorithm didn’t see, you test whether the patterns that you found in the first subset are robust and are also observed in the unseen subjects.
This is a very powerful way to assess how strong and replicable the impact on the microbiome is of a given variable. We could quantify that discreetly, and we did so for all of the variables in the dataset and we ranked them by importance.
TS: What recommendations do you have for microbiologists or folks reading about microbiology?
IVC: Based on these findings, we put forth the recommendation for human microbiome studies to capture information on these variables. These are two things that were not typically collected as part of clinical studies, whereas age, BMI, and sex more typically are. We recommend an expansion of the variables that are collected into terms of information and if possible to match these variables between the groups that are being compared, because they have an impact on the microbiome, and we want to mitigate how much studies are actually looking at these effects of these confounding variables and instead narrow down their results to what’s really of interest in the disease that is that is being studied.
I.V.C. et al., “Host variables confound gut microbiota studies of human disease” Nature, doi:10.1038/s41586-020-2881-9, 2020.


thescientist--2020-11-06--Doctors Consider Convalescent T Cell Therapy for COVID-19

Physicians and researchers have had questionable success treating patients with severe COVID-19 with either antibody-based drugs or convalescent plasma .
Neither of those strategies is a cell-based therapy , and , in a preprint posted October 26 on bioRxiv , researchers propose collecting SARS-CoV-2–specific memory T cells from recovered individuals , banking the cells , and infusing them into patients as a treatment for infections .
“ There are data now that are coming out from the analysis of the immune response that are suggesting that the T cells are more important for protection than antibodies , ” says Antonio @ @ @ @ @ @ @ immunological therapies at Duke-NUS Medical School in Singapore and did not participate in the work .
There is therefore a rationale to use T cells to control the disease , he adds .
Previously , researchers had attempted memory T cell therapy to suppress cytomegalovirus and Epstein Barr virus .
The recipients were leukemia patients who received a stem cell transplant to treat their cancer at the same time .
It was this success , combined with the T cell findings from COVID-19 patients , that led Antonio Pérez-Martínez , a pediatrician at @ @ @ @ @ @ @ , and his colleagues to consider a cell-based treatment for the coronavirus .
The researchers isolated memory T cells , including some that released interferon gamma , a cytokine necessary for anti-viral immunity , upon exposure to SARS-CoV-2 antigens , from the blood of people who recovered from COVID-19 .
They showed that it was possible to freeze , store , and thaw these cells and propose that biobanks of memory T cells could be created from convalescent donors to be infused to treat disease .
The practice of storing convalescent plasma , @ @ @ @ @ @ @ , to treat COVID-19 patients is already in wide use , although with mixed data on its utility .
“ If you give plasma and antibodies , those antibodies could potentially fight COVID , but they are not produced in that person , so they are just have a normal half-life and they are cleared , ” says Rory de Vries , an immunologist at Erasmus University Medical Center in the Netherlands who did not participate in the study .
But when T cells encounter a virus , “ they start expanding , @ @ @ @ @ @ @ new immunological memory while you ’ re doing that , which will never happen with plasma.
” Despite the theoretical potential , “ it ’ s not an easy approach , ” de Vries cautions .
For one thing , the authors “ don ’ t only store SARS-CoV-2 specific T cells , they store every memory cell , so that means that you also store your memory for measles or .
.
.
previous vaccinations , ” he tells The Scientist .
“ And if you infuse these T cells , I @ @ @ @ @ @ @ what might happen.
” In a cell-based treatment , there are also concerns about immunological compatibility of the donor and recipient , just as there would be during an organ transplant , de Vries explains .
The authors did characterize memory T cells based on human leukocyte antigens ( HLA ) , molecules responsible for the immune system ’ s ability to distinguish self and non-self .
But de Vries cautions that HLA diversity is vast , potentially requiring more extensive characterization than the authors have done in the preprint to make the @ @ @ @ @ @ @ the HLA matching is sufficient because patients with severe COVID-19 have lymphopenia , a dearth of white blood cells called lymphocytes , a subtype of which are T cells .
Lymphopenia is a biological marker of severe COVID-19 , he says .
The patients who are more lymphopenic have a greater chance of ending up in the ICU and eventually dying .
The lymphopenia triggered by the coronavirus is similar to the lymphopenia induced by chemotherapy drugs in patients before a stem cell transplant , so the transplant won ’ t be rejected @ @ @ @ @ @ @ window ” during COVID-19 is the time at which it could be possible to replace a patient ’ s missing lymphocytes with SARS-CoV-2-responsive T cells from recovered donors .
The idea is that lymphopenic patients don ’ t have enough of their own T cells , so they ’ re not going to reject donor lymphocytes .
This strategy “ is complicated and needs some work , ” says Bertoletti .
“ It could be that for a short time .
.
.
when you are introducing these T cells in a patient @ @ @ @ @ @ @ suppress viral replication and kill the infected cells , ” he adds , but the unanswered questions of how important HLA matching is and what the appropriate timing for such a treatment complicates matters .
In order to test the safety of the treatment , Pérez-Martínez and colleagues are beginning a Phase I clinical trial in patients hospitalized for COVID-19 with lymphopenia .
In the transplant setting , doctors have not seen any side effects , he says , “ so I think that it ’ s worth it to try.
” C. @ @ @ @ @ @ @ memory T lymphocytes from COVID-19 convalescent donors : identification , biobanking and large-scale production for Adoptive Cell Therapy , ” bioRxiv , doi:10.1101/2020.10.23.352294 , 2020 .

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Physicians and researchers have had questionable success treating patients with severe COVID-19 with either antibody-based drugs or convalescent plasma. Neither of those strategies is a cell-based therapy, and, in a preprint posted October 26 on bioRxiv, researchers propose collecting SARS-CoV-2–specific memory T cells from recovered individuals, banking the cells, and infusing them into patients as a treatment for infections.
“There are data now that are coming out from the analysis of the immune response that are suggesting that the T cells are more important for protection than antibodies,” says Antonio Bertoletti, who studies the development of immunological therapies at Duke-NUS Medical School in Singapore and did not participate in the work. There is therefore a rationale to use T cells to control the disease, he adds.
Previously, researchers had attempted memory T cell therapy to suppress cytomegalovirus and Epstein Barr virus. The recipients were leukemia patients who received a stem cell transplant to treat their cancer at the same time. It was this success, combined with the T cell findings from COVID-19 patients, that led Antonio Pérez-Martínez, a pediatrician at Hospital Infantil Universitario La Paz in Madrid, and his colleagues to consider a cell-based treatment for the coronavirus.
The researchers isolated memory T cells, including some that released interferon gamma, a cytokine necessary for anti-viral immunity, upon exposure to SARS-CoV-2 antigens, from the blood of people who recovered from COVID-19. They showed that it was possible to freeze, store, and thaw these cells and propose that biobanks of memory T cells could be created from convalescent donors to be infused to treat disease. The practice of storing convalescent plasma, which includes antibodies but no immune cells, to treat COVID-19 patients is already in wide use, although with mixed data on its utility.
“If you give plasma and antibodies, those antibodies could potentially fight COVID, but they are not produced in that person, so they are just have a normal half-life and they are cleared,” says Rory de Vries, an immunologist at Erasmus University Medical Center in the Netherlands who did not participate in the study. But when T cells encounter a virus, “they start expanding, and you might actually build your own new immunological memory while you’re doing that, which will never happen with plasma.”
Despite the theoretical potential, “it’s not an easy approach,” de Vries cautions. For one thing, the authors “don’t only store SARS-CoV-2 specific T cells, they store every memory cell, so that means that you also store your memory for measles or . . . previous vaccinations,” he tells The Scientist. “And if you infuse these T cells, I don’t think we really know what might happen.”
In a cell-based treatment, there are also concerns about immunological compatibility of the donor and recipient, just as there would be during an organ transplant, de Vries explains. The authors did characterize memory T cells based on human leukocyte antigens (HLA), molecules responsible for the immune system’s ability to distinguish self and non-self. But de Vries cautions that HLA diversity is vast, potentially requiring more extensive characterization than the authors have done in the preprint to make the treatment safe.
According to Pérez-Martínez, the HLA matching is sufficient because patients with severe COVID-19 have lymphopenia, a dearth of white blood cells called lymphocytes, a subtype of which are T cells. Lymphopenia is a biological marker of severe COVID-19, he says. The patients who are more lymphopenic have a greater chance of ending up in the ICU and eventually dying.
The lymphopenia triggered by the coronavirus is similar to the lymphopenia induced by chemotherapy drugs in patients before a stem cell transplant, so the transplant won’t be rejected, he explains. This “lymphopenic window” during COVID-19 is the time at which it could be possible to replace a patient’s missing lymphocytes with SARS-CoV-2-responsive T cells from recovered donors. The idea is that lymphopenic patients don’t have enough of their own T cells, so they’re not going to reject donor lymphocytes.
This strategy “is complicated and needs some work,” says Bertoletti. “It could be that for a short time . . . when you are introducing these T cells in a patient, they will be basically able to suppress viral replication and kill the infected cells,” he adds, but the unanswered questions of how important HLA matching is and what the appropriate timing for such a treatment complicates matters.
In order to test the safety of the treatment, Pérez-Martínez and colleagues are beginning a Phase I clinical trial in patients hospitalized for COVID-19 with lymphopenia. In the transplant setting, doctors have not seen any side effects, he says, “so I think that it’s worth it to try.”
C. Ferreras et al., “SARS-CoV-2 specific memory T lymphocytes from COVID-19 convalescent donors: identification, biobanking and large-scale production for Adoptive Cell Therapy,” bioRxiv, doi:10.1101/2020.10.23.352294, 2020.


Foolproofing Microbiome Workflows

When studying diverse microbiomes , scientists can easily become overwhelmed by the resources , organization , and technical expertise needed @ @ @ @ @ , many modern technologies address the pain points surrounding microbiome research .
Download this infographic @ @ @ @ @ to optimize each step of complex microbiome workflows .

When studying diverse microbiomes, scientists can easily become overwhelmed by the resources, organization, and technical expertise needed for accurate analysis. Luckily, many modern technologies address the pain points surrounding microbiome research.
Download this infographic from Eppendorf to learn how to optimize each step of complex microbiome workflows.


thescientist--2020-11-09--Pfizer's COVID-19 Vaccine 90 Percent Effective: Initial Data

Preliminary data from pharmaceutical giant Pfizer and German biotechnology firm BioNTech show that their COVID-19 vaccine is more than 90 percent effective at protecting people from the infection , compared to patients who received a placebo saline shot , according to a Pfizer statement today ( November 9 ) .
“ I ’ ve been in vaccine development for 35 years , ” William Gruber , Pfizer ’ s senior vice president of vaccine clinical research and development , tells STAT .
“ I ’ ve seen some really good things .
This is extraordinary.
” He added , “ @ @ @ @ @ @ @ able to get a handle on the epidemic and get us out of this situation.
” While it ’ s unclear exactly how many of the trial ’ s 43,000 participants , who received either two doses of the vaccine or the placebo , have contracted COVID-19 , the interim analysis includes 94 confirmed cases .
Among these 94 , roughly 10 percent had been given the vaccine , while the other 90 percent had been given a placebo .
Anthony Fauci , the director of the National Institute of Allergy and Infectious @ @ @ @ @ @ @ results suggesting 90 percent efficacy are “ just extraordinary .
Not very many people expected it would be as high as that.
” Scientists have warned that a COVID-19 vaccine may be only as good as an influenza vaccine , which is about 50 percent effective and requires yearly shots .
Earlier this year , Fauci said he would be excited by a COVID-19 vaccine that was 75 percent effective .
If the final vaccine ends up with that level of efficacy , it “ would be higher than your regular flu vaccine @ @ @ @ @ @ @ serious impact on bending the curve of this outbreak , ” Saad Omer , the director of the Yale Institute for Global Health who is not involved in the development of COVID-19 vaccines , tells The New York Times .
The companies have not yet released the full results of the analysis , which has not been peer-reviewed by outside experts or published in a medical journal .
There is also no information yet on the severity of the infections among those who were vaccinated .
See “ Trials Unlikely to Show if @ @ @ @ @ @ @ If that headline number really holds up , that is huge .
That is much better than I was expecting , and it will make a huge difference , ” Ashish Jha , the dean of the School of Public Health at Brown University who is not involved in the development of COVID-19 vaccines , tells STAT .
He adds that it is difficult to evaluate science from a press release and that he looks forward to reviewing the full results .
Pfizer plans to continue its study until it records 164 infections @ @ @ @ @ @ @ efficacy in accordance with the US Food and Drug Administration ’ s ( FDA ) guidelines .
FDA officials require any COVID-19 vaccine to be at least 50 percent effective to consider approval .
Members of the independent data monitoring board that reviewed the results found no serious safety concerns .
They reported similar side effects to an earlier study of the vaccine that was posted in August on a preprint server : pain at the injection site , fatigue , chills , and fever—which occurred more frequently in older and younger trial @ @ @ @ @ @ @ If a vaccine is authorized , initial supplies will be scarce and rationed , with priority likely to be given to front-line workers such as healthcare employees .
Pfizer has estimated that it could make available 50 million doses globally by the end of 2020 , which would vaccinate 25 million people because it ’ s administered in two doses .

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Update (November 18): After the companies concluded their Phase 3 trials and found that the vaccine is 95 percent effective in an analysis of 170 confirmed COVID-19 cases, Pfizer and BioNTech are expected to seek emergency authorization from global regulators within days. The results put the vaccine on par with competitor Moderna’s COVID-19 vaccine, which was found on Monday to be 94.5 percent effective in a preliminary analysis of 95 participants.
Preliminary data from pharmaceutical giant Pfizer and German biotechnology firm BioNTech show that their COVID-19 vaccine is more than 90 percent effective at protecting people from the infection, compared to patients who received a placebo saline shot, according to a Pfizer statement today (November 9).
“I’ve been in vaccine development for 35 years,” William Gruber, Pfizer’s senior vice president of vaccine clinical research and development, tells STAT. “I’ve seen some really good things. This is extraordinary.” He added, “This really bodes well for us being able to get a handle on the epidemic and get us out of this situation.”
While it’s unclear exactly how many of the trial’s 43,000 participants, who received either two doses of the vaccine or the placebo, have contracted COVID-19, the interim analysis includes 94 confirmed cases. Among these 94, roughly 10 percent had been given the vaccine, while the other 90 percent had been given a placebo.
Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, tells the Associated Press the results suggesting 90 percent efficacy are “just extraordinary. Not very many people expected it would be as high as that.”
Scientists have warned that a COVID-19 vaccine may be only as good as an influenza vaccine, which is about 50 percent effective and requires yearly shots. Earlier this year, Fauci said he would be excited by a COVID-19 vaccine that was 75 percent effective.
If the final vaccine ends up with that level of efficacy, it “would be higher than your regular flu vaccine, and this vaccine could have a serious impact on bending the curve of this outbreak,” Saad Omer, the director of the Yale Institute for Global Health who is not involved in the development of COVID-19 vaccines, tells The New York Times.
The companies have not yet released the full results of the analysis, which has not been peer-reviewed by outside experts or published in a medical journal. There is also no information yet on the severity of the infections among those who were vaccinated.
“If that headline number really holds up, that is huge. That is much better than I was expecting, and it will make a huge difference,” Ashish Jha, the dean of the School of Public Health at Brown University who is not involved in the development of COVID-19 vaccines, tells STAT. He adds that it is difficult to evaluate science from a press release and that he looks forward to reviewing the full results.
Pfizer plans to continue its study until it records 164 infections among all the volunteers to demonstrate its efficacy in accordance with the US Food and Drug Administration’s (FDA) guidelines. FDA officials require any COVID-19 vaccine to be at least 50 percent effective to consider approval.
Members of the independent data monitoring board that reviewed the results found no serious safety concerns. They reported similar side effects to an earlier study of the vaccine that was posted in August on a preprint server: pain at the injection site, fatigue, chills, and fever—which occurred more frequently in older and younger trial participants than in those aged 18–65.
If a vaccine is authorized, initial supplies will be scarce and rationed, with priority likely to be given to front-line workers such as healthcare employees. Pfizer has estimated that it could make available 50 million doses globally by the end of 2020, which would vaccinate 25 million people because it’s administered in two doses.


thescientist--2020-11-09--Correct Weight Handling: Ten Practical Tips

Scientists precisely calibrate and test laboratory balances with reference weights .
These weights are very sensitive to the smallest perturbations @ @ @ @ @ , and microabrasions .
To ensure their long-term accuracy , scientists must carefully care for @ @ @ @ @ .
Download this infographic from Mettler Toldeo to learn ten practical tips for proper reference @ @ @ @ @ and handling .

Weighing reagents may not even show up as a line item on a scientist’s to-do list, but this everyday step is essential for experimental success, accurate data interpretation, and reproducibility of experimental results. Performing some precise but simple calibration steps will ensure that your balance—and its resulting measurements—stay trustworthy.
Download this infographic from Mettler Toledo to learn how to safeguard the accuracy of your laboratory balance.


thescientist--2020-11-09--Optimizing Samples for RNA Sequencing

Optimizing Samples for RNA Sequencing

Single-cell sequencing is widely used in basic , applied , and translational research .
The high sensitivity of scRNA seq @ @ @ @ @ to reduce sequencing noise and data variability .
Factors such as poor viability , cellular @ @ @ @ @ abundance influence sample preparation for RNA sequencing .
Download this white paper from Sony to @ @ @ @ @ the quality of single-cell RNA sequencing results .

Single-cell sequencing is widely used in basic, applied, and translational research. The high sensitivity of scRNA seq requires careful processing of cells to reduce sequencing noise and data variability. Factors such as poor viability, cellular heterogeneity, and target cell abundance influence sample preparation for RNA sequencing.
Download this white paper from Sony to learn how sample optimization influences the quality of single-cell RNA sequencing results.


thescientist--2020-11-09--Modern Approaches to qPCR

Modern Approaches to qPCR

Scientists use quantitative PCR ( qPCR ) for a variety of sensitive applications , from multiplexed gene expression profiling to @ @ @ @ @ small amounts of genetic material are exponentially amplified , small errors can lead to large @ @ @ @ @ share optimal results , scientists turn to modern qPCR instruments that offer improved thermal uniformity @ @ @ @ @ this ebook from The Scientist 's Creative Services team and Bio-Rad to learn about

Scientists use quantitative PCR (qPCR) for a variety of sensitive applications, from multiplexed gene expression profiling to infectious disease diagnostics. Because small amounts of genetic material are exponentially amplified, small errors can lead to large problems. To obtain and share optimal results, scientists turn to modern qPCR instruments that offer improved thermal uniformity and cloud connectivity.
Download this ebook from The Scientist's Creative Services team and Bio-Rad to learn about


thescientist--2020-11-09--Sample Processing During a Pandemic

Sample Processing During a Pandemic

To meet the need for rapid and large-scale COVID-19 diagnostics , scientists at clinical laboratories pivoted their resources and efforts @ @ @ @ @ new diagnostic laboratories dedicated to COVID-19 testing sprang to life .
Scientists in these laboratories @ @ @ @ @ adapting sample accessioning and processing workflows to meet the unprecedented demand for rapid , reliable @ @ @ @ @ .
Download this ebook from LGC , Biosearch Technologies to learn about • How laboratories @ @ @ @ @ demand for large-scale sample accessioning and testing • Key insights into improving testing workflows from @ @ @ @ @ epidemiology and infectious disease diagnostic developer at the Center for Infection and Immunity at Columbia @ @ @ @

To meet the need for rapid and large-scale COVID-19 diagnostics, scientists at clinical laboratories pivoted their resources and efforts to COVID-19 testing, and new diagnostic laboratories dedicated to COVID-19 testing sprang to life. Scientists in these laboratories faced the unique challenge of adapting sample accessioning and processing workflows to meet the unprecedented demand for rapid, reliable, and accurate diagnostic testing.
Download this ebook from LGC, Biosearch Technologies to learn about