thescientist--2020-08-28--Bacteria-Laced Mosquitoes Limit Spread of Dengue

ABOVE : A researcher hold up a plate of mosquitoes .
MONASH UNIVERSITY Mosquito-borne diseases such as malaria , dengue , and Zika sicken nearly 700 million people each year , and the preliminary results of a new study hint at a possible way of drastically minimizing the spread of such illnesses .
Researchers have infected Aedes aegypti mosquitoes—the species responsible for passing on many diseases—with bacteria called Wolbachia with the intent of reducing the insects ’ ability to pass on dengue to people .
When these modified mosquitoes were released in the Indonesian city of Yogyakarta , the rates @ @ @ @ @ @ @ two years , making it four times less likely that a person would contract the disease by the end of the study than in years past .
“ It is a huge breakthrough , ” Nicholas Jewell , a biostatistician at the University of California , Berkeley , who designed the study , said in an August 26 press release announcing the findings .
While the full data behind the study are yet to be released , Jewell says the success in one city is promising .
“ If this can be replicated @ @ @ @ @ @ @ dengue from several parts of the world for many years.
” Detailed results will be shared at an international scientific congress in November , The Guardian reports .
The Yogyakarta trial is the culmination of a decade of laboratory and field work based on methods pioneered by Scott O ’ Neill , a microbiologist at the University of Monash and director of the World Mosquito Project ( WMP ) , who first began manipulating mosquitoes in the 1990s .
He had previously shown that Wolbachia reduced transmission of dengue by mosquitoes , and @ @ @ @ @ @ @ were lower in the Australian city of Townsville after Wolbachia-infected mosquitoes were released , although that study failed to include controls and tracked much smaller outbreaks than those in countries where dengue is endemic .
In the newest study , the first controlled trial to use the Wolbachia method , the team divided the city of Yogyakarta into 24 regions in a checkerboard pattern and released modified mosquitoes into 12 of them , retaining the remaining dozen as controls .
In total , about 6 million mosquitoes were released over six months across @ @ @ @ @ @ @ 312,000 people , The Guardian reports .
These mosquitoes go on to mate ( but not reproduce ) with local wild populations , transferring the bacteria to naive mosquitoes .
The scientists partnered with local clinics to track the number of people coming in with fevers that could be attributed to dengue , back-tracking their movements to see which of the areas of the city they lived in or had visited within the previous 10 days .
After more than two years , 8,144 people between the ages of three and 45 were @ @ @ @ @ @ @ call the “ golden number ” of a 77 percent reduction in the rate of dengue diagnoses in clusters where the mosquitoes had been released .
“ This exciting result of the trial is a great success for the people of Yogyakarta , ” Adi Utarini , a researcher of public health quality at the University of Gadjah Mad and co-principal investigator of the trial , says in the press release .
“ Indonesia has 7 million dengue cases every year .
This trial result shows the significant impact the Wolbachia method can @ @ @ @ @ @ @ ” Scientists still do not fully understand how Wolbachia inhibits transmission of the virus that causes dengue when the two pathogens inhabit the same mosquito .
Katie Anders , the director of impact assessment at the WMP , tells The Guardian it may be that the two compete for the same resources .
“ By having bacteria there it might prevent the virus from growing , and or [ the bacteria ] might elicit an immune response in the mosquito that ’ s protective against the virus , ” Anders says .
Despite @ @ @ @ @ @ @ next step is to treat the rest of the city , releasing mosquitoes in areas that had previously served as controls .
In addition , similar initiatives have been carried out in at least 11 other countries where dengue is endemic , according to the authors .
Singapore , an island city-state off the coast of Malaysia , is currently experiencing a record-breaking year for dengue , Reuters reports , with more than 26,000 reported cases .
Local scientists are releasing up to six Wolbachia mosquitoes each week for every person living in @ @ @ @ @ @ @ , the WMP aims to release Wolbachia mosquitoes in areas covering 75 million people at risk of dengue in the next five years , Nature reports , increasing their reach to half a billion people in the next decade .
Expansion of the program will depend upon an influx of funding spurred by this successful trial .
Independent economists have suggested that the mosquito releases , estimated to cost up to $ 21 per person , will pay for themselves within a few years by reducing healthcare costs , lost income , and @ @ @ @ @ @ @ reports .
And while the initiative has so far looked at dengue , the same technique has the potential to limit transmission for a host of other mosquito-borne diseases , including Zika , chikungunya , and yellow fever .
Immo Kleinshmidt , an epidemiologist at the London School of Hygiene and Tropical Medicine who was part of an independent board monitoring the trial , says the positive results will likely result in broad support .
“ I suspect that the demand for this intervention from dengue-endemic countries will result in widespread introduction of @ @ @ @ @ @ @ of eventually eliminating the disease , ” Kleinschmidt tells Nature .
“ The significance of this result is epochal .
”

ABOVE: A researcher hold up a plate of mosquitoes.
MONASH UNIVERSITY
Mosquito-borne diseases such as malaria, dengue, and Zika sicken nearly 700 million people each year, and the preliminary results of a new study hint at a possible way of drastically minimizing the spread of such illnesses.
Researchers have infected Aedes aegypti mosquitoes—the species responsible for passing on many diseases—with bacteria called Wolbachia with the intent of reducing the insects’ ability to pass on dengue to people. When these modified mosquitoes were released in the Indonesian city of Yogyakarta, the rates of dengue dropped by 77 percent over two years, making it four times less likely that a person would contract the disease by the end of the study than in years past.
“It is a huge breakthrough,” Nicholas Jewell, a biostatistician at the University of California, Berkeley, who designed the study, said in an August 26 press release announcing the findings. While the full data behind the study are yet to be released, Jewell says the success in one city is promising. “If this can be replicated and used widely, it could eradicate dengue from several parts of the world for many years.” Detailed results will be shared at an international scientific congress in November, The Guardian reports.
The Yogyakarta trial is the culmination of a decade of laboratory and field work based on methods pioneered by Scott O’Neill, a microbiologist at the University of Monash and director of the World Mosquito Project (WMP), who first began manipulating mosquitoes in the 1990s. He had previously shown that Wolbachia reduced transmission of dengue by mosquitoes, and he later demonstrated that cases of dengue were lower in the Australian city of Townsville after Wolbachia-infected mosquitoes were released, although that study failed to include controls and tracked much smaller outbreaks than those in countries where dengue is endemic.
In the newest study, the first controlled trial to use the Wolbachia method, the team divided the city of Yogyakarta into 24 regions in a checkerboard pattern and released modified mosquitoes into 12 of them, retaining the remaining dozen as controls. In total, about 6 million mosquitoes were released over six months across an area that is home to around 312,000 people, The Guardian reports. These mosquitoes go on to mate (but not reproduce) with local wild populations, transferring the bacteria to naive mosquitoes.
The scientists partnered with local clinics to track the number of people coming in with fevers that could be attributed to dengue, back-tracking their movements to see which of the areas of the city they lived in or had visited within the previous 10 days. After more than two years, 8,144 people between the ages of three and 45 were included to arrive at what the authors call the “golden number” of a 77 percent reduction in the rate of dengue diagnoses in clusters where the mosquitoes had been released.
“This exciting result of the trial is a great success for the people of Yogyakarta,” Adi Utarini, a researcher of public health quality at the University of Gadjah Mad and co-principal investigator of the trial, says in the press release. “Indonesia has 7 million dengue cases every year. This trial result shows the significant impact the Wolbachia method can have in reducing dengue in urban populations.”
See “How Bacteria Interfere with Insect Reproduction”
Scientists still do not fully understand how Wolbachia inhibits transmission of the virus that causes dengue when the two pathogens inhabit the same mosquito. Katie Anders, the director of impact assessment at the WMP, tells The Guardian it may be that the two compete for the same resources. “By having bacteria there it might prevent the virus from growing, and or [the bacteria] might elicit an immune response in the mosquito that’s protective against the virus,” Anders says.
Despite these unknowns, the team says the next step is to treat the rest of the city, releasing mosquitoes in areas that had previously served as controls. In addition, similar initiatives have been carried out in at least 11 other countries where dengue is endemic, according to the authors.
Singapore, an island city-state off the coast of Malaysia, is currently experiencing a record-breaking year for dengue, Reuters reports, with more than 26,000 reported cases. Local scientists are releasing up to six Wolbachia mosquitoes each week for every person living in the most high-risk areas.
Moving forward, the WMP aims to release Wolbachia mosquitoes in areas covering 75 million people at risk of dengue in the next five years, Nature reports, increasing their reach to half a billion people in the next decade.
Expansion of the program will depend upon an influx of funding spurred by this successful trial. Independent economists have suggested that the mosquito releases, estimated to cost up to $21 per person, will pay for themselves within a few years by reducing healthcare costs, lost income, and other losses attributed to dengue, Nature reports. And while the initiative has so far looked at dengue, the same technique has the potential to limit transmission for a host of other mosquito-borne diseases, including Zika, chikungunya, and yellow fever.
Immo Kleinshmidt, an epidemiologist at the London School of Hygiene and Tropical Medicine who was part of an independent board monitoring the trial, says the positive results will likely result in broad support. “I suspect that the demand for this intervention from dengue-endemic countries will result in widespread introduction of this method, with a good prospect of eventually eliminating the disease,” Kleinschmidt tells Nature. “The significance of this result is epochal.”


thescientist--2020-08-28--U of Illinois Returns to School with 20,000 Saliva Tests Per Day

ABOVE : An individual submits a saliva test at the University of Illinois UNIVERSITY OF ILLINOIS The University of Illinois Urbana-Champaign announced in June that when students , faculty , and staff returned to campus for the fall semester , every individual would undergo rapid saliva testing for COVID-19 twice a week in order to swiftly quell any outbreaks .
To process the 20,000 tests conducted each day , the university repurposed its veterinary lab .
To take the test , a person only needs to spit into a tube , then the sample is heated for 30 minutes and @ @ @ @ @ @ @ sample for RT-qPCR .
Each test costs $ 10 .
The school budgeted $ 6 million for startup costs and up to $ 10 million for testing throughout the semester .
The initiative is supported by a cell phone app that immediately notifies individuals of their test results and can alert them if they ’ ve been in close contact with someone who has tested positive .
Those who test positive are quarantined .
Now , that plan is being put in place as school is getting underway .
See “ Saliva Tests @ @ @ @ @ @ @ Bring to COVID-19 ” The Scientist spoke with Martin Burke , a chemist at the university who helped develop the saliva test , about how the initiative has gone so far .
The Scientist : First , can you tell me about the tests that you developed that you ’ re using to do this mass testing ?
Martin Burke : Sure .
So back in April , we launched a project to try to figure out how to stand up and strategically deploy standard testing as part of the university ’ s @ @ @ @ @ @ @ .
And we quickly realized that the standard nasal swab viral transfer media RNA isolation was not going to be sufficient .
[ It would be ] too slow , too expensive , and have too many supply chain bottlenecks .
So I teamed up with my colleague Paul Hergenrother [ another chemist at the university ] and launched kind of a Manhattan Project–style effort to find a way to test cheaper , faster , and without the supply chain bottlenecks .
Paul led an extraordinary team of students and postdocs and a @ @ @ @ @ @ @ could skip the RNA isolation step , go directly from saliva to PCR , and thereby get rid of most of the supply chain bottlenecks , dramatically increase the speed , and reduce the cost .
This is the backbone of the programs .
TS : Can you describe a little bit about the program itself , how it ’ s set up ?
MB : The testing itself is not a silver bullet—we wrap around it frontier data science to figure out who to test and how frequently to repeat it .
@ @ @ @ @ @ @ have ] rapid communication to a new app that was created for the phone by Bill Sullivan and his team so that you get your results immediately pushed straight to your phone in a HIPAA-complaint and fully privacy-protected manner as well as digital exposure notifications .
So between all of that is this test .
And we had to get to 20,000 tests per day in order to be able to meet the demand of twice per week for 60,000 people .
I ’ m very excited to tell you we achieved that @ @ @ @ @ @ @ seen so far ?
MB : We ran a pilot over the summer with all the student staff who were here .
And actually in mid-July , we had a spike .
There was a social event that led to an increase .
But then by just having frequent testing across the summer , over the next two weeks , we watched it fall down so I think that was our first indication that this really had a shot .
We knew we were going to get a bump when all the students @ @ @ @ @ @ @ just as we predicted with the modeling .
And I ’ m so excited to tell you , we ’ re watching it fall as we do the frequent repeat testing on the population right now .
We really hope that this is going to continue to show a way which we could get society reopened .
TS : Now that everybody ’ s back , how are they responding to the strategy ?
MB : So far , we ’ ve seen a remarkable level of compliance .
The goal , of @ @ @ @ @ @ @ safely isolated , help people get safely quarantined .
A lot of them don ’ t mind it so much because they get free food and lots of support and they get a care package .
We don ’ t want to make it feel like they ’ ve done something wrong , we just want to make everyone feel safe and protected .
We talk to business owners to try to create a true understanding of how important and exciting this is , an opportunity to invest in staying open .
So @ @ @ @ @ @ @ imposed a shutdown of indoor bars and restaurants for a two- to three-week period as the students came back to try to avoid superspreader events .
I was really excited to see this driving home the other night [ as I ] passed a fraternity house .
The guys had brought out their ping pong table , out on the front yard with their masks on playing ping pong .
And I ’ ll tell you , that is when I knew we were going to make it .
Editor ’ s note @ @ @ @ @ @ @ .

ABOVE: An individual submits a saliva test at the University of Illinois
UNIVERSITY OF ILLINOIS
The University of Illinois Urbana-Champaign announced in June that when students, faculty, and staff returned to campus for the fall semester, every individual would undergo rapid saliva testing for COVID-19 twice a week in order to swiftly quell any outbreaks. To process the 20,000 tests conducted each day, the university repurposed its veterinary lab. To take the test, a person only needs to spit into a tube, then the sample is heated for 30 minutes and scientists add chemical reagents to prepare the sample for RT-qPCR. Each test costs $10. The school budgeted $6 million for startup costs and up to $10 million for testing throughout the semester.
The initiative is supported by a cell phone app that immediately notifies individuals of their test results and can alert them if they’ve been in close contact with someone who has tested positive. Those who test positive are quarantined. Now, that plan is being put in place as school is getting underway.
The Scientist spoke with Martin Burke, a chemist at the university who helped develop the saliva test, about how the initiative has gone so far.
The Scientist: First, can you tell me about the tests that you developed that you’re using to do this mass testing?
Martin Burke: Sure. So back in April, we launched a project to try to figure out how to stand up and strategically deploy standard testing as part of the university’s effort to reopen as safely as possible. And we quickly realized that the standard nasal swab viral transfer media RNA isolation was not going to be sufficient. [It would be] too slow, too expensive, and have too many supply chain bottlenecks. So I teamed up with my colleague Paul Hergenrother [another chemist at the university] and launched kind of a Manhattan Project–style effort to find a way to test cheaper, faster, and without the supply chain bottlenecks.
Paul led an extraordinary team of students and postdocs and a bunch of us together and found we could skip the RNA isolation step, go directly from saliva to PCR, and thereby get rid of most of the supply chain bottlenecks, dramatically increase the speed, and reduce the cost. This is the backbone of the programs.
TS: Can you describe a little bit about the program itself, how it’s set up?
MB: The testing itself is not a silver bullet—we wrap around it frontier data science to figure out who to test and how frequently to repeat it. And then on the backend [we have] rapid communication to a new app that was created for the phone by Bill Sullivan and his team so that you get your results immediately pushed straight to your phone in a HIPAA-complaint and fully privacy-protected manner as well as digital exposure notifications. So between all of that is this test. And we had to get to 20,000 tests per day in order to be able to meet the demand of twice per week for 60,000 people. I’m very excited to tell you we achieved that.
TS: And what have you seen so far?
MB: We ran a pilot over the summer with all the student staff who were here. And actually in mid-July, we had a spike. There was a social event that led to an increase. But then by just having frequent testing across the summer, over the next two weeks, we watched it fall down so I think that was our first indication that this really had a shot.
We knew we were going to get a bump when all the students came back. We got it, just as we predicted with the modeling. And I’m so excited to tell you, we’re watching it fall as we do the frequent repeat testing on the population right now. We really hope that this is going to continue to show a way which we could get society reopened.
TS: Now that everybody’s back, how are they responding to the strategy?
MB: So far, we’ve seen a remarkable level of compliance. The goal, of course, is to help people get safely isolated, help people get safely quarantined. A lot of them don’t mind it so much because they get free food and lots of support and they get a care package. We don’t want to make it feel like they’ve done something wrong, we just want to make everyone feel safe and protected.
We talk to business owners to try to create a true understanding of how important and exciting this is, an opportunity to invest in staying open. So, for example, the community voluntarily imposed a shutdown of indoor bars and restaurants for a two- to three-week period as the students came back to try to avoid superspreader events.
I was really excited to see this driving home the other night [as I] passed a fraternity house. The guys had brought out their ping pong table, out on the front yard with their masks on playing ping pong. And I’ll tell you, that is when I knew we were going to make it.
Editor’s note: The interview was edited for brevity.


thescientist--2020-08-24--Adoptive Cell Therapy Summit

Adoptive Cell Therapy Summit

In the field of immuno-oncology , adoptive cell therapy is widely recognized for its promise to elicit effective long-term anti-cancer immunity .
Cancer immunotherapy harnesses the power of the immune system by adoptively transferring tumor-infiltrating lymphocytes or modified peripheral blood immune cells into cancer patients to mediate long lasting anti-tumor responses .
During this summit , leading scientists in the field of cancer immunotherapy will present their research and perspectives on : • Characterization of cellular phenotype and function prior to T cell expansion High Content Functional and Phenotypic Flow Cytometric Analysis of TILs : Guidance for Therapy and Improvement @ @ @ @ @ @ @ , PhD , FRCP ( London ) Professor , University Hospital in Mainz ( Germany ) Head of Immunotherapy/Immunosurgery Program Champalimaud Foundation , Portugal Biology and Efficacy of Synthetic Antigen Receptors that Signal via the TCR Jonathan Bramson , PhD Vice-Dean Research , Faculty of Health Sciences Professor , Pathology and Molecular Medicine , McMaster University Canada Research Chair in Translational Cancer Immunology CSO , Triumvira Immunologics Understanding Resistance to Develop Better CAR T Immunotherapies Marco Ruella , MD Assistant Professor of Medicine Scientific Director Lymphoma Program Center for Cellular Immunotherapies University of @ @ @ @ @ @ @ Treatment : Progress and Challenges Christine E. Brown , PhD Heritage Provider Network Professor in Immunotherapy Deputy Director , T-cell Therapeutics Research Laboratory Department of Hematology & Hematopoietic Cell Transplantation City of Hope Comprehensive Cancer Center

FREE Summit
Tuesday, September 22, 2020
10:00 AM - 1:30 PM, Eastern Standard Time
Register Now
In the field of immuno-oncology, adoptive cell therapy is widely recognized for its promise to elicit effective long-term anti-cancer immunity. Cancer immunotherapy harnesses the power of the immune system by adoptively transferring tumor-infiltrating lymphocytes or modified peripheral blood immune cells into cancer patients to mediate long lasting anti-tumor responses.
During this summit, leading scientists in the field of cancer immunotherapy will present their research and perspectives on:
Mechanisms underlying T cell signaling and efficacy
Characterization of cellular phenotype and function prior to T cell expansion
Factors influencing T cell performance when treating aggressive and challenging cancers
Summit program
Biology and Efficacy of Synthetic Antigen Receptors that Signal via the TCR
Jonathan Bramson, PhD
Vice-Dean Research, Faculty of Health Sciences
Professor, Pathology and Molecular Medicine, McMaster University
Canada Research Chair in Translational Cancer Immunology
CSO, Triumvira Immunologics
Understanding Resistance to Develop Better CAR T Immunotherapies
Marco Ruella, MD
Assistant Professor of Medicine
Scientific Director Lymphoma Program
Center for Cellular Immunotherapies
University of Pennsylvania
Advancing CAR T Cells for Glioblastoma Treatment: Progress and Challenges
Christine E. Brown, PhD
Heritage Provider Network Professor in Immunotherapy
Deputy Director, T-cell Therapeutics Research Laboratory
Department of Hematology & Hematopoietic Cell Transplantation
City of Hope Comprehensive Cancer Center
High Content Functional and Phenotypic Flow Cytometric Analysis of TILs: Guidance for Therapy and Improvement of Product Development
Markus Maeurer, MD, PhD, FRCP (London)
Head of Immunotherapy/Immunosurgery Program
Champalimaud Foundation, Portugal
I Med Clinical, University of Mainz, Germany
Register Now
Summit sponsored by


thescientist--2020-08-31--Blood Replacement Rescues Mice from Stroke Damage

Researchers have partially mitigated the effects of an ischemic stroke in mice simply by replacing a small amount of their blood with that of a healthy donor .
Days after receiving the transplant , mice had less tissue damage surrounding the clot and suffered fewer neurological side effects compared to mice that had not received a blood infusion .
The results , published August 25 in Nature Communications , highlight the link between strokes in the brain and the immune system .
At least some of the damage caused by strokes , the authors say , is the result of @ @ @ @ @ @ @ sent to an injury to fight infection and facilitate repair instead harm sensitive brain tissue .
“ The initial impetus for the study was to determine the extent to which this immune response , which we know is very rapid and very profound , contributes to brain damage from stroke , ” James Simpkins , a neuroscientist at West Virginia University and a coauthor of the paper , tells The Scientist .
In the moments following a stroke , the body activates a complex immunological response , funneling messenger molecules past the blood-brain @ @ @ @ @ @ @ immune cells to the damaged area .
Neutrophils—white blood cells that are often the first to arrive—increase the levels of an enzyme called MMP-9 that degrades the blood-brain barrier further , the better to allow more immune cells and signaling molecules to pass through .
In some instances , the body can release too many of these molecules , such as cytokines , into the blood at once , and the resulting cytokine storm can damage brain tissue surrounding a clot , causing inflammation and degeneration of brain tissue .
To better understand @ @ @ @ @ @ @ , the researchers used a mouse model to mimic an ischemic stroke that was subsequently cleared by the scientists after 90 minutes .
Between six and seven hours after the stroke , the mice received a blood transfusion of either 250 or 500 microliters of blood from a healthy donor , roughly 10 percent to 20 percent of a mouse ’ s total blood volume , after the same volume had been removed from the animal .
One hour later , the scientists tested the permeability of the blood-brain barrier , followed by @ @ @ @ @ @ @ brain tissue 24 hours after treatment .
Mice that received blood replacements suffered fewer ill effects than control mice , with the benefits being strongest in the group receiving a larger volume of new blood .
The extent of tissue damage surrounding the clot decreased by as much as 70 percent to 80 percent , and cognitive defects brought on by the stroke improved in treated mice .
Both the decrease in tissue damage and the rescuing of neurological deficits persisted for at least three days after the initial stroke .
“ This @ @ @ @ @ @ @ Hermann , a neuroscientist at the University Hospital in Essen who was not part of the study , tells The Scientist .
“ This study clearly shows that there is a lot of promise in utilizing the capacity of blood of healthy animals .
.
.
which opens ideas for additional studies.
” Having established that blood replacement does in fact benefit mice following a stroke , Simpkins and his colleagues began looking into which components of blood are responsible for what he calls “ the magic.
” When mice had blood transfused @ @ @ @ @ @ @ not see the same benefits—the healthy donor was key .
In addition , the mice did not improve when given plasma .
Something in the cellular fraction of the blood itself was essential to the therapy .
See `` Glowing Proteins Enable Stem Cell Stimulation for Stroke Recovery in Mice '' The broader effect of replacing blood seems to be a dampening of the immune response .
Following the treatment , the authors measured fewer leukocytes , including neutrophils , monocytes , T cells , and B cells , circulating in the mice @ @ @ @ @ @ @ true for chemokines and other cytokines , and they also found that MMP-9 was lower in the circulating blood and brains of treated mice , resulting in less degradation of the blood-brain barrier .
When mice were given blood with MMP-9 artificially increased , the efficacy of the treatment was greatly reduced .
Xuefang “ Sophie ” Ren , a neuroscientist at West Virginia University and the first author on the study , says this last finding suggests that a reduction of MMP-9 brought on by a decrease in neutrophils in treated mice @ @ @ @ @ @ @ ’ s success .
While she is already pursuing this idea in new research , the team will still need to carefully study each cell type to assess its individual importance and the ways in which cell types interact .
“ We still have a lot of work to do to identify the roles of these different cell types in stroke , ” Ren says .
If the team members can identify the most important molecular components in the blood , they could target them for either enrichment or depletion in a mouse @ @ @ @ @ @ @ donor .
For example , if neutrophils are found to be detrimental through their relationship to MMP-9 , they could aim to reduce neutrophils in blood following a stroke .
Alternatively , if they can identify a beneficial component , they could add it back in .
Despite these early successes , it ’ s unlikely that blood replacement would ever supplant existing therapies , says Francesca Bosetti , the program director for stroke at the National Institute of Neurological Disorders and Stroke , although it could be used in tandem .
For @ @ @ @ @ @ @ used simulated a stroke followed by a recovery—something achieved in people by administering a clot-busting drug or endovascular treatment to restore blood flow to the brain prior to the blood replacement .
“ Nevertheless , if this new intervention can buy additional time or improve the outcome , then it would be extremely important , ” Bosetti says .
( The National Institutes of Health partly funded the study . )
To bring the treatment to humans , both Bosetti and Hermann say , a critical next step is to test blood replacement @ @ @ @ @ @ @ cohort of mice .
Each experiment in the study included between five and eight individuals .
“ In experimental systems you have extremely standardized conditions , so one mouse is like the next one , ” Hermann tells The Scientist .
“ But keep in mind patients have very heterogeneous strokes .
Whether such a black-and-white response can be expected in human patients remains enigmatic.
” The authors would need to include both female and male mice—the current study included only males—across different age categories and with a broader suite of comorbidities reflective @ @ @ @ @ @ @ In addition , Bosetti says she would like to see a more comprehensive assessment of cognitive and motor functions in addition to measuring infarct volume , as well as more sophisticated analyses of the blood-brain barrier .
“ Then , if these are all pointing to the right direction , one could consider potential clinical trials.
” X. Ren et al.
, “ Blood substitution therapy rescues the brain of mice from ischemic damage , ” Nat Commun , doi:10.1038/s41467-020-17930-x , 2020 .

Mice treated with healthy donor blood following a stroke had less brain tissue death than control mice, as evidenced by less white material in the brain slices. When mice were given donor blood containing MMP-9, an enzyme that degrades the blood-brain barrier, the benefit of the blood replacement therapy was minimized. REN ET AL., NAT COMMUN, 11:4078, 2020
Researchers have partially mitigated the effects of an ischemic stroke in mice simply by replacing a small amount of their blood with that of a healthy donor. Days after receiving the transplant, mice had less tissue damage surrounding the clot and suffered fewer neurological side effects compared to mice that had not received a blood infusion.
The results, published August 25 in Nature Communications, highlight the link between strokes in the brain and the immune system. At least some of the damage caused by strokes, the authors say, is the result of an overreactive immune response during which cells sent to an injury to fight infection and facilitate repair instead harm sensitive brain tissue.
“The initial impetus for the study was to determine the extent to which this immune response, which we know is very rapid and very profound, contributes to brain damage from stroke,” James Simpkins, a neuroscientist at West Virginia University and a coauthor of the paper, tells The Scientist.
In the moments following a stroke, the body activates a complex immunological response, funneling messenger molecules past the blood-brain barrier and into the blood to recruit immune cells to the damaged area. Neutrophils—white blood cells that are often the first to arrive—increase the levels of an enzyme called MMP-9 that degrades the blood-brain barrier further, the better to allow more immune cells and signaling molecules to pass through. In some instances, the body can release too many of these molecules, such as cytokines, into the blood at once, and the resulting cytokine storm can damage brain tissue surrounding a clot, causing inflammation and degeneration of brain tissue.
To better understand the immunological link between brain and blood, the researchers used a mouse model to mimic an ischemic stroke that was subsequently cleared by the scientists after 90 minutes. Between six and seven hours after the stroke, the mice received a blood transfusion of either 250 or 500 microliters of blood from a healthy donor, roughly 10 percent to 20 percent of a mouse’s total blood volume, after the same volume had been removed from the animal. One hour later, the scientists tested the permeability of the blood-brain barrier, followed by a measure of the amount of damaged brain tissue 24 hours after treatment.
Mice that received blood replacements suffered fewer ill effects than control mice, with the benefits being strongest in the group receiving a larger volume of new blood. The extent of tissue damage surrounding the clot decreased by as much as 70 percent to 80 percent, and cognitive defects brought on by the stroke improved in treated mice. Both the decrease in tissue damage and the rescuing of neurological deficits persisted for at least three days after the initial stroke.
“This is solid stroke research,” Dirk Hermann, a neuroscientist at the University Hospital in Essen who was not part of the study, tells The Scientist. “This study clearly shows that there is a lot of promise in utilizing the capacity of blood of healthy animals . . . which opens ideas for additional studies.”
Having established that blood replacement does in fact benefit mice following a stroke, Simpkins and his colleagues began looking into which components of blood are responsible for what he calls “the magic.” When mice had blood transfused from other stroke mice, they did not see the same benefits—the healthy donor was key. In addition, the mice did not improve when given plasma. Something in the cellular fraction of the blood itself was essential to the therapy.
See "Glowing Proteins Enable Stem Cell Stimulation for Stroke Recovery in Mice"
The broader effect of replacing blood seems to be a dampening of the immune response. Following the treatment, the authors measured fewer leukocytes, including neutrophils, monocytes, T cells, and B cells, circulating in the mice’s blood. The same was true for chemokines and other cytokines, and they also found that MMP-9 was lower in the circulating blood and brains of treated mice, resulting in less degradation of the blood-brain barrier. When mice were given blood with MMP-9 artificially increased, the efficacy of the treatment was greatly reduced.
Xuefang “Sophie” Ren, a neuroscientist at West Virginia University and the first author on the study, says this last finding suggests that a reduction of MMP-9 brought on by a decrease in neutrophils in treated mice hints at a mechanism behind the therapy’s success. While she is already pursuing this idea in new research, the team will still need to carefully study each cell type to assess its individual importance and the ways in which cell types interact. “We still have a lot of work to do to identify the roles of these different cell types in stroke,” Ren says.
If the team members can identify the most important molecular components in the blood, they could target them for either enrichment or depletion in a mouse’s existing blood without a separate donor. For example, if neutrophils are found to be detrimental through their relationship to MMP-9, they could aim to reduce neutrophils in blood following a stroke. Alternatively, if they can identify a beneficial component, they could add it back in.
Despite these early successes, it’s unlikely that blood replacement would ever supplant existing therapies, says Francesca Bosetti, the program director for stroke at the National Institute of Neurological Disorders and Stroke, although it could be used in tandem. For instance, the mouse model the team used simulated a stroke followed by a recovery—something achieved in people by administering a clot-busting drug or endovascular treatment to restore blood flow to the brain prior to the blood replacement. “Nevertheless, if this new intervention can buy additional time or improve the outcome, then it would be extremely important,” Bosetti says. (The National Institutes of Health partly funded the study.)
To bring the treatment to humans, both Bosetti and Hermann say, a critical next step is to test blood replacement therapies on a larger, more diverse cohort of mice. Each experiment in the study included between five and eight individuals. “In experimental systems you have extremely standardized conditions, so one mouse is like the next one,” Hermann tells The Scientist. “But keep in mind patients have very heterogeneous strokes. Whether such a black-and-white response can be expected in human patients remains enigmatic.”
The authors would need to include both female and male mice—the current study included only males—across different age categories and with a broader suite of comorbidities reflective of what is seen in humans. In addition, Bosetti says she would like to see a more comprehensive assessment of cognitive and motor functions in addition to measuring infarct volume, as well as more sophisticated analyses of the blood-brain barrier. “Then, if these are all pointing to the right direction, one could consider potential clinical trials.”
X. Ren et al., “Blood substitution therapy rescues the brain of mice from ischemic damage,” Nat Commun, doi:10.1038/s41467-020-17930-x, 2020.


thescientist--2020-08-31--Ingenza meets a key milestone in the deployment of novel cost-effective COVID-19 vaccine technology

Ingenza has been working closely with researchers at Oxford University and the UK CPI , Wilton , since the start of the outbreak , and the collaboration is continuing to make excellent progress .
The team ’ s latest milestone success is the efficient production , using engineered yeast , of the receptor-binding domain ( RBD ) of the SARS-CoV-2 spike protein .
When displayed on a novel virus-like particle ( VLP ) – developed and produced by the Oxford team also using a recombinant microbe – the resulting prototype vaccine elicits a powerful immunogenic response in mouse studies .
@ @ @ @ @ @ @ ’ s unique combination of bioprocessing skills , including decades of experience and expertise in molecular biology .
Downstream assays are now underway to validate and optimise the production technology for pre-clinical testing and , if successful , this will lead to a novel and cost-effective fully-microbial biomanufacturing platform to support rapid scale-up and high adaptability for future vaccine needs .
Ian Fotheringham , Managing Director of Ingenza , commented : “ It is a huge privilege to be involved with our collaborators on this project and the progress we are making is @ @ @ @ @ @ @ proud to be applying our expertise in sustainable and cost-effective biomanufacturing to this global crisis and look forward to helping the world ’ s scientists develop a novel COVID-19 vaccine .
”

Ingenza has been working closely with researchers at Oxford University and the UK CPI, Wilton, since the start of the outbreak, and the collaboration is continuing to make excellent progress.
The team’s latest milestone success is the efficient production, using engineered yeast, of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. When displayed on a novel virus-like particle (VLP) – developed and produced by the Oxford team also using a recombinant microbe – the resulting prototype vaccine elicits a powerful immunogenic response in mouse studies.
The results stem from the Scottish company’s unique combination of bioprocessing skills, including decades of experience and expertise in molecular biology. Downstream assays are now underway to validate and optimise the production technology for pre-clinical testing and, if successful, this will lead to a novel and cost-effective fully-microbial biomanufacturing platform to support rapid scale-up and high adaptability for future vaccine needs.
Ian Fotheringham, Managing Director of Ingenza, commented: “It is a huge privilege to be involved with our collaborators on this project and the progress we are making is extremely positive and exciting. We are proud to be applying our expertise in sustainable and cost-effective biomanufacturing to this global crisis and look forward to helping the world’s scientists develop a novel COVID-19 vaccine.”


thescientist--2020-09-01--Book Excerpt from How Zoologists Organize Things

The oldest Western traditions of naming and classifying animals arose from the Judaeo-Christian tradition , and zoological organization certainly has a prominent place in the Scriptures .
Adam was created on the same day as the beasts of the Earth—a surprising nod to the modern concept of “ man as an animal ” —and one of the very first tasks assigned to him was to name those beasts .
Indeed , it is notable that God only decided to create Eve because his non-human creations were not up to the task of accompanying and helping Adam .
This biblical trope @ @ @ @ @ @ @ and is perhaps partly explained by , detailed proscriptions against eating certain animals .
Leviticus , Chapter XI contains what we would now call “ decision trees ” relating to the eating of animals with cloven hooves , that chew the cud , or that have fins and scales .
It is possible that these rules derived from earlier trial-and-error experiments with different foodstuffs , which led , presumably , to some disastrous microbiological or parasitic consequences , and these rules survive in modern Jewish customs .
The reader can not help feeling @ @ @ @ @ @ @ have had a practical life-or-death rationale , and indeed practical considerations have often driven our need to classify animals .
After all we , by definition , are the descendants of people who knew which beasts were ferocious or toxic .
The other ancestral strand of Western zoological classification is the ancient Greeks , whose writings seem to spring from an enlightened inquisitiveness rather than a crude need to survive .
Indeed , at first sight , their approach appears surprisingly modern .
Much of early Greek animal biology is summarized in Aristotle @ @ @ @ @ @ @ although it can sometimes be difficult to distinguish Aristotle ’ s own discoveries from those of his often-uncredited sources .
Aristotle lived and wrote on Lesbos , one of the largest islands in the Aegean Sea , and his descriptions of the island ’ s fauna , especially those that inhabited its warm , shallow lagoons , form the basis of much of the Natural Philosophy .
Aristotle continually emphasized that his writings were based on observation of nature itself and not a repetition of the errors of his predecessors , and to @ @ @ @ @ @ @ each ζ ?
ον ( “ zoön ” means “ animal , ” hence “ zoology ” ) he encountered , he analyzed particular traits he thought could be used to determine its affinities with other creatures .
He realized that some features are common to all animals , and also that color , shape and size are unreliable classificatory criteria .
As a result , he recommended organizing animals according to the following categories : their food , habitat and behavior , how they breathe , whether they metamorphose , whether they @ @ @ @ @ @ @ diurnal , tame or wild , offensive or defensive , whether they lay eggs or bear live young , whether they are anchored to the seabed or swim , walk , wriggle or fly free .
Yet Aristotle ’ s thinking was not quite as modern as sometimes credited .
Although he produced the first known “ scientific ” classification of animals , he was still bound by the wider metaphysical structure into which he wished to fit the world .
He was an early proponent of the scala naturae , the ascending @ @ @ @ @ @ @ all things are ranked in a carefully gradated ladder of ascent from base matter , through plants , animals and humans to the divine .
This strict hierarchical classification , although at odds with the sprawling animal diversity Aristotle himself described , was to form the basis of many later zoological classifications , and indeed philosophy in general until the nineteenth century .
It placed man reassuringly above the beasts , and set him ( for it was usually assumed to be a “ him ” ) on a journey along a scale @ @ @ @ @ @ @ the formless and base towards the divine .
However , Aristotle himself provided evidence that the scala was an imperfect concept—he often seems to consider humans to be “ just another animal , ” for example—yet it proved to be one of his most tenacious ideas .
Written by an unknown hand , probably in the second century AD , in Alexandria , the Physiologus is the next waypoint on the journey to modern animal classification .
In many ways , it set the tone for over a thousand years .
It is @ @ @ @ @ @ @ Christian religion , and the forty animals it describes are presented less according to their zoological attributes , and more for what they can tell us as religious symbols .
Each creature acquires a role in the Christian story , drawing on the earlier Greek traditions of animal parables , to illustrate particular theological principles .
In the Physiologus , animals serve merely as illustrative elements of the word of God—zoology had become subservient to theology , and for centuries the scientific coherence of the former discipline was to suffer as a result @ @ @ @ @ @ @ traditions came in the early seventh century with the Etymologiae of Isidore of Seville .
Isidore ’ s book was an enormous undertaking , ostensibly an early attempt to create an encyclopedia of all contemporary knowledge .
Yet it was skewed by the author ’ s opinions about which ancient ideas were deemed deserving of perpetuation .
Also , as the book ’ s name suggests , Isidore believed that discovering the origin of particular words was the key to understanding the ideas they denote .
So , for example , he saw @ @ @ @ @ @ @ as directly philosophically equivalent to the very nature of the large grey pachyderm—whereas the modern reader would simply assume that concepts can be used to name animals ( a sloth , for example ) , and animals can give their names to concepts ( as in a “ dogfight ” ) .
Indeed , in the long story of animal classification , the Etymlogiae is perhaps the instance when the human urge to organize animals most outstripped our actual understanding of those animals .
However , the tome was endlessly reproduced throughout medieval @ @ @ @ @ @ @ became immensely influential .
These , then , were the forerunners of animal classification in the Late Middle Ages .
Aristotle ’ s metaphysics , Isidore ’ s obsession with names , and Christianity ’ s inward-looking self-justification led directly to the first and one of the most artistically spectacular bodies of zoological organization : the bestiary .
Medieval bestiaries flourished , especially in France , England and Scotland in the twelfth and thirteenth centuries , and while their level of artistic achievement varies , they were surprisingly consistent in their structure and @ @ @ @ @ @ @ their compilers draw on previous and contemporary works for their inspiration , that the evolution of medieval bestiaries can itself be arranged into an evolutionary genealogy , with works fitting neatly into “ family ” lineages of relatedness and descent .
The mainly north African animals of the Physiologus were supplemented with north European creatures , as well as mythical beasts , to yield a rich menagerie from which theological lessons could be extracted .
Spectacular illustrations presumably made these parables accessible to the illiterate masses , and it is not known whether @ @ @ @ @ @ @ animals depicted actually existed .
In bestiaries animals have a meaning beyond their actual physical nature , so their existence or otherwise is less important than what they can tell us about God .
Some symbolism was straightforward—a fox traps birds as the devil ensnares sinners ; a panther mauls a dragon as Jesus attacks Satan .
However , some animals , especially those with which medieval readers were more familiar , could be complex characters—a goat might be a sinner swallowed by hell in one context , and then the all-seeing sage @ @ @ @ @ @ @ that became popular in the Middle Ages was the mappa mundi , in which stylized geographies of the entire world ( i.e .
God ’ s creation ) were summarized in giant cartographic images .
In most , the three known continents , Asia , Africa and Europe , are arranged around a centrally placed Jerusalem , a reassurance of God ’ s place at the centre of the world .
Around their periphery , however , lie strange lands , inhabited by exotic and horrific creatures—often distortions of real animals formulated to @ @ @ @ @ @ @ animal/human chimaeric hybrids .
Some of the most dramatic examples of this zoological otherness appear towards the edges of the Hereford mappa mundi ( see page 26 ) where dog-headed people or cynocephali , perhaps based on accounts of real-life baboons , can be seen frolicking .
During the Renaissance , thinking began to change .
The religious certainty of medieval cataloguing started to give way to more objective attempts at classification .
The sixteenth century saw the publication of works such as the Swiss philosopher Conrad Gessner ’ s meticulous Historiae Animalium @ @ @ @ @ @ @ , with his vast collection of zoological curiosities in Bologna , and his De Piscibus and Ornithologiae among many other books .
The sheer variety of animal life was rendering old ideas of a neat scala naturae untenable .
The “ steppiness ” of the scala ’ s ladder of creation was starting to look less clear-cut .
Indeed , its neat linear progression from base matter to godhead now seemed an oversimplification .
One day this stepwise ascent of animal creation would be transformed into a branching tree , and other more @ @ @ @ @ @ @ artist .
Excerpted from How Zoologists Organize Things : The Art of Classification by David Bainbridge .
Copyright David Bainbridge , 2020 .
Frances Lincoln .
All rights reserved .

The oldest Western traditions of naming and classifying animals arose from the Judaeo-Christian tradition, and zoological organization certainly has a prominent place in the Scriptures. Adam was created on the same day as the beasts of the Earth—a surprising nod to the modern concept of “man as an animal”—and one of the very first tasks assigned to him was to name those beasts. Indeed, it is notable that God only decided to create Eve because his non-human creations were not up to the task of accompanying and helping Adam.
This biblical trope of animal classification continues later in, and is perhaps partly explained by, detailed proscriptions against eating certain animals. Leviticus, Chapter XI contains what we would now call “decision trees” relating to the eating of animals with cloven hooves, that chew the cud, or that have fins and scales. It is possible that these rules derived from earlier trial-and-error experiments with different foodstuffs, which led, presumably, to some disastrous microbiological or parasitic consequences, and these rules survive in modern Jewish customs. The reader cannot help feeling that many of these arcane injunctions must have had a practical life-or-death rationale, and indeed practical considerations have often driven our need to classify animals. After all we, by definition, are the descendants of people who knew which beasts were ferocious or toxic.
The other ancestral strand of Western zoological classification is the ancient Greeks, whose writings seem to spring from an enlightened inquisitiveness rather than a crude need to survive. Indeed, at first sight, their approach appears surprisingly modern. Much of early Greek animal biology is summarized in Aristotle’s fourth-century BC Natural Philosophy, although it can sometimes be difficult to distinguish Aristotle’s own discoveries from those of his often-uncredited sources.
Aristotle lived and wrote on Lesbos, one of the largest islands in the Aegean Sea, and his descriptions of the island’s fauna, especially those that inhabited its warm, shallow lagoons, form the basis of much of the Natural Philosophy. Aristotle continually emphasized that his writings were based on observation of nature itself and not a repetition of the errors of his predecessors, and to some extent this is true. For each ζ?ον (“zoön” means “animal,” hence “zoology”) he encountered, he analyzed particular traits he thought could be used to determine its affinities with other creatures. He realized that some features are common to all animals, and also that color, shape and size are unreliable classificatory criteria. As a result, he recommended organizing animals according to the following categories: their food, habitat and behavior, how they breathe, whether they metamorphose, whether they are social or solitary, nocturnal or diurnal, tame or wild, offensive or defensive, whether they lay eggs or bear live young, whether they are anchored to the seabed or swim, walk, wriggle or fly free.
Yet Aristotle’s thinking was not quite as modern as sometimes credited. Although he produced the first known “scientific” classification of animals, he was still bound by the wider metaphysical structure into which he wished to fit the world. He was an early proponent of the scala naturae, the ascending “ladder of nature” by which all things are ranked in a carefully gradated ladder of ascent from base matter, through plants, animals and humans to the divine. This strict hierarchical classification, although at odds with the sprawling animal diversity Aristotle himself described, was to form the basis of many later zoological classifications, and indeed philosophy in general until the nineteenth century. It placed man reassuringly above the beasts, and set him (for it was usually assumed to be a “him”) on a journey along a scale of progress towards perfection, away from the formless and base towards the divine. However, Aristotle himself provided evidence that the scala was an imperfect concept—he often seems to consider humans to be “just another animal,” for example—yet it proved to be one of his most tenacious ideas.
Written by an unknown hand, probably in the second century AD, in Alexandria, the Physiologus is the next waypoint on the journey to modern animal classification. In many ways, it set the tone for over a thousand years. It is infused with the philosophy of the new Christian religion, and the forty animals it describes are presented less according to their zoological attributes, and more for what they can tell us as religious symbols. Each creature acquires a role in the Christian story, drawing on the earlier Greek traditions of animal parables, to illustrate particular theological principles. In the Physiologus, animals serve merely as illustrative elements of the word of God—zoology had become subservient to theology, and for centuries the scientific coherence of the former discipline was to suffer as a result.
A strange detour in these zoological traditions came in the early seventh century with the Etymologiae of Isidore of Seville. Isidore’s book was an enormous undertaking, ostensibly an early attempt to create an encyclopedia of all contemporary knowledge. Yet it was skewed by the author’s opinions about which ancient ideas were deemed deserving of perpetuation. Also, as the book’s name suggests, Isidore believed that discovering the origin of particular words was the key to understanding the ideas they denote. So, for example, he saw the concept of being “elephantine” as directly philosophically equivalent to the very nature of the large grey pachyderm—whereas the modern reader would simply assume that concepts can be used to name animals (a sloth, for example), and animals can give their names to concepts (as in a “dogfight”). Indeed, in the long story of animal classification, the Etymlogiae is perhaps the instance when the human urge to organize animals most outstripped our actual understanding of those animals. However, the tome was endlessly reproduced throughout medieval Europe and the Islamic world, and became immensely influential.
These, then, were the forerunners of animal classification in the Late Middle Ages. Aristotle’s metaphysics, Isidore’s obsession with names, and Christianity’s inward-looking self-justification led directly to the first and one of the most artistically spectacular bodies of zoological organization: the bestiary.
Medieval bestiaries flourished, especially in France, England and Scotland in the twelfth and thirteenth centuries, and while their level of artistic achievement varies, they were surprisingly consistent in their structure and focus. Indeed, so much did their compilers draw on previous and contemporary works for their inspiration, that the evolution of medieval bestiaries can itself be arranged into an evolutionary genealogy, with works fitting neatly into “family” lineages of relatedness and descent. The mainly north African animals of the Physiologus were supplemented with north European creatures, as well as mythical beasts, to yield a rich menagerie from which theological lessons could be extracted. Spectacular illustrations presumably made these parables accessible to the illiterate masses, and it is not known whether their audience worried about which of the animals depicted actually existed. In bestiaries animals have a meaning beyond their actual physical nature, so their existence or otherwise is less important than what they can tell us about God. Some symbolism was straightforward—a fox traps birds as the devil ensnares sinners; a panther mauls a dragon as Jesus attacks Satan. However, some animals, especially those with which medieval readers were more familiar, could be complex characters—a goat might be a sinner swallowed by hell in one context, and then the all-seeing sage Christ in another.
Another visual format that became popular in the Middle Ages was the mappa mundi, in which stylized geographies of the entire world (i.e. God’s creation) were summarized in giant cartographic images. In most, the three known continents, Asia, Africa and Europe, are arranged around a centrally placed Jerusalem, a reassurance of God’s place at the centre of the world. Around their periphery, however, lie strange lands, inhabited by exotic and horrific creatures—often distortions of real animals formulated to scare the faithful, or even devilish animal/human chimaeric hybrids. Some of the most dramatic examples of this zoological otherness appear towards the edges of the Hereford mappa mundi (see page 26) where dog-headed people or cynocephali, perhaps based on accounts of real-life baboons, can be seen frolicking.
During the Renaissance, thinking began to change. The religious certainty of medieval cataloguing started to give way to more objective attempts at classification. The sixteenth century saw the publication of works such as the Swiss philosopher Conrad Gessner’s meticulous Historiae Animalium. Fifty years later came Ulisse Aldrovandi, with his vast collection of zoological curiosities in Bologna, and his De Piscibus and Ornithologiae among many other books. The sheer variety of animal life was rendering old ideas of a neat scala naturae untenable.
The “steppiness” of the scala’s ladder of creation was starting to look less clear-cut. Indeed, its neat linear progression from base matter to godhead now seemed an oversimplification. One day this stepwise ascent of animal creation would be transformed into a branching tree, and other more alien forms never conceived by the medieval artist.
Excerpted from How Zoologists Organize Things: The Art of Classification by David Bainbridge. Copyright David Bainbridge, 2020. Frances Lincoln. All rights reserved.


thescientist--2020-09-01--Long-Lasting Wound Infections Linked to Microbes and Genetics

ABOVE : Pathogenic bacteria such as Staphylococcus epidermidis , shown here , are more likely to emerge in wounds in which the diversity of other microbes is low .
© ISTOCK.COM , KSASS C. Tipton et al.
, “ Patient genetics is linked to chronic wound microbiome composition and healing , ” PLOS Pathog , 16 : e1008511 , 2020 .
How quickly scrapes , cuts , and gashes in the skin heal can vary greatly depending on a person ’ s body mass , age , and whether the individual suffers from certain chronic conditions such as diabetes .
@ @ @ @ @ @ @ may also play a role , with variations in two specific genes lowering the diversity of a wound ’ s microbiome and lengthening healing time .
Through a partnership with Southwest Regional Wound Care Center in Lubbock , Texas , geneticist Caleb Phillips at Texas Tech University and colleagues gained access to 85 patients ’ DNA samples .
Analyzing each person ’ s sample and comparing it to the diversity of bacteria in the patient ’ s infected wound , the team found that individuals with specific single nucleotide polymorphisms ( SNPs ) @ @ @ @ @ @ @ actin assembly , and ZNF521 , which encodes a transcription factor , had lower overall microbial diversity in their wounds and were much more likely to suffer from Pseudomonas and Staphylococcus infections .
Those patients ’ skin injuries were also much slower to heal , suggesting that individuals with these specific TLN2 and ZNF521 mutations may be at higher risk of developing chronic wounds .
Despite the “ modest sample size , ” Phillips says , the study offers a better understanding of what makes a patient vulnerable to chronic wounds .
The @ @ @ @ @ @ @ ZNF521 could serve as biomarkers to identify patients at risk for slow wound recovery , he notes .
The extent of the microbiome ’ s role in chronic wounds is “ a really big question in the field of healing and repair , ” notes Lindsay Kalan , a medical microbiologist and immunologist at the University of Wisconsin–Madison who was not involved in the study .
While the paper ’ s results are “ not immediately translatable ” for patient care , she says , it is “ definitely a step in the @ @ @ @

ABOVE: Pathogenic bacteria such as Staphylococcus epidermidis, shown here, are more likely to emerge in wounds in which the diversity of other microbes is low.
© ISTOCK.COM, KSASS
EDITOR’S CHOICE IN GENETICS & GENOMICS
The paper
C. Tipton et al., “Patient genetics is linked to chronic wound microbiome composition and healing,” PLOS Pathog, 16:e1008511, 2020.
How quickly scrapes, cuts, and gashes in the skin heal can vary greatly depending on a person’s body mass, age, and whether the individual suffers from certain chronic conditions such as diabetes. Genetics, a new study suggests, may also play a role, with variations in two specific genes lowering the diversity of a wound’s microbiome and lengthening healing time.
Through a partnership with Southwest Regional Wound Care Center in Lubbock, Texas, geneticist Caleb Phillips at Texas Tech University and colleagues gained access to 85 patients’ DNA samples. Analyzing each person’s sample and comparing it to the diversity of bacteria in the patient’s infected wound, the team found that individuals with specific single nucleotide polymorphisms (SNPs) in TLN2, a gene involved in actin assembly, and ZNF521, which encodes a transcription factor, had lower overall microbial diversity in their wounds and were much more likely to suffer from Pseudomonas and Staphylococcus infections. Those patients’ skin injuries were also much slower to heal, suggesting that individuals with these specific TLN2 and ZNF521 mutations may be at higher risk of developing chronic wounds.
Despite the “modest sample size,” Phillips says, the study offers a better understanding of what makes a patient vulnerable to chronic wounds. The SNPs the team described in TLN2 and ZNF521 could serve as biomarkers to identify patients at risk for slow wound recovery, he notes.
The extent of the microbiome’s role in chronic wounds is “a really big question in the field of healing and repair,” notes Lindsay Kalan, a medical microbiologist and immunologist at the University of Wisconsin–Madison who was not involved in the study. While the paper’s results are “not immediately translatable” for patient care, she says, it is “definitely a step in the right direction.”


Back to School

My wife and I , like parents across the US and beyond , are grappling with a very difficult situation at the moment : the start of another school year for our children amidst rampant COVID-19 spread in our state and country .
Our local school district has decided that its more than 18,000 students will start the 2020–21 school year with a “ remote for all ” educational model .
Kids from 3 to 18 years old , including our preschooler and two elementary school students , will log in to virtual classrooms to meet with teachers , interact @ @ @ @ @ @ @ that had to be reenvisioned in the face of the disruption and forced flexibility wrought by the ongoing pandemic .
We followed along intently via livestreamed meetings as our district school board hashed out the details of the coming academic year , hoping that evidence-based thinking and appropriately proportioned risk avoidance would guide its decisions .
By and large that was the case , and our board heeded warnings and guidance from state and federal public health agencies .
Other schools , including private schools in our area , have chosen to invite @ @ @ @ @ @ @ back into classrooms with precautions designed to reduce the risk of SARS-CoV-2 transmission .
Frankly , I feel for the cohort that is returning to schools in person this fall .
Especially for teachers , who are perennially underappreciated , underpaid , and overworked , being forced back into the classroom seems to add insult to historical injury .
In effect , they must choose between their vocation and their health , between the needs of their students and the safety of themselves and their loved ones .
My consternation arises from facts @ @ @ @ @ @ @ schools across the nation returned to in-person instruction in late May .
Within days , one Jerusalem high school reported that 154 students and 26 staff members had tested positive for SARS-CoV-2 .
Infections rippled into their communities .
Eli Waxman , a researcher at the Weizmann Institute of Science and chairman of the team advising Israel ’ s National Security Council on reopening schools , shared some advice in early August for other countries weighing the benefits and drawbacks of opening schools .
“ They definitely should not do what we have @ @ @ @ @ @ @ York Times .
“ It was a major failure.
” Israel made its decision to reopen at a time when the country was reporting fewer than 100 new infections per day .
As of this writing ( in mid-August ) , on the eve of many US schools opening their doors , America is seeing an average of more than 56,000 new cases per day , according to the US Centers for Disease Control and Prevention .
Indeed , in Georgia , schools in a suburban district north of Atlanta opened on August @ @ @ @ @ @ @ 1,200 students and staff members had been ordered to quarantine due to COVID-19 outbreaks at more than 10 schools .
I consider these episodes to be clear cautionary tales .
Adding to this anecdotal evidence is the evolving science surrounding the susceptibility of young people .
Recent research has combated notions of adolescents being less susceptible to SARS-CoV-2 infection , and in fact has suggested that children who contract the virus may carry higher viral loads than adults .
To be sure , I am aware of the fact that for children , @ @ @ @ @ @ @ forum .
For most , it fulfills vital social needs for peer interaction .
And for too many , even for kids within my own district , school offers a respite from abuse , hunger , or an otherwise chaotic or uncertain home life .
Taking away that refuge represents something much more dangerous than a delay or alteration in the educational process .
But for the millions engaging in virtual learning this semester , I am hopeful that parents , students , and teachers can view the situation in a light that @ @ @ @ @ @ @ as usual .
I am hopeful that my own kids and others in their classes will cultivate valuable skills and thought patterns as they navigate the technological and social realities before them .
After all , even before the pandemic changed so much about life in 2020 , the world was becoming ever more connected , virtual , and off-site .
There is a strong probability that the next generation will be learning or working remotely in their lifetimes .
So at the start of another school year , one that none of @ @ @ @ @ @ @ staff members , teachers , school board members , students , and parents who are braving our new normal , and urge them to see the positive in this difficult situation .

ABOVE: © istock.com, RAWF8
My wife and I, like parents across the US and beyond, are grappling with a very difficult situation at the moment: the start of another school year for our children amidst rampant COVID-19 spread in our state and country. Our local school district has decided that its more than 18,000 students will start the 2020–21 school year with a “remote for all” educational model. Kids from 3 to 18 years old, including our preschooler and two elementary school students, will log in to virtual classrooms to meet with teachers, interact with classmates, and follow a curriculum that had to be reenvisioned in the face of the disruption and forced flexibility wrought by the ongoing pandemic.
We followed along intently via livestreamed meetings as our district school board hashed out the details of the coming academic year, hoping that evidence-based thinking and appropriately proportioned risk avoidance would guide its decisions. By and large that was the case, and our board heeded warnings and guidance from state and federal public health agencies. Other schools, including private schools in our area, have chosen to invite teachers, students, and staff members back into classrooms with precautions designed to reduce the risk of SARS-CoV-2 transmission. Frankly, I feel for the cohort that is returning to schools in person this fall. Especially for teachers, who are perennially underappreciated, underpaid, and overworked, being forced back into the classroom seems to add insult to historical injury. In effect, they must choose between their vocation and their health, between the needs of their students and the safety of themselves and their loved ones.
My consternation arises from facts on the ground. In Israel, schools across the nation returned to in-person instruction in late May. Within days, one Jerusalem high school reported that 154 students and 26 staff members had tested positive for SARS-CoV-2. Infections rippled into their communities. Eli Waxman, a researcher at the Weizmann Institute of Science and chairman of the team advising Israel’s National Security Council on reopening schools, shared some advice in early August for other countries weighing the benefits and drawbacks of opening schools. “They definitely should not do what we have done,” he told The New York Times. “It was a major failure.”
Andrzej Krauze
Israel made its decision to reopen at a time when the country was reporting fewer than 100 new infections per day. As of this writing (in mid-August), on the eve of many US schools opening their doors, America is seeing an average of more than 56,000 new cases per day, according to the US Centers for Disease Control and Prevention. Indeed, in Georgia, schools in a suburban district north of Atlanta opened on August 3. By August 12, nearly 1,200 students and staff members had been ordered to quarantine due to COVID-19 outbreaks at more than 10 schools.
I consider these episodes to be clear cautionary tales. Adding to this anecdotal evidence is the evolving science surrounding the susceptibility of young people. Recent research has combated notions of adolescents being less susceptible to SARS-CoV-2 infection, and in fact has suggested that children who contract the virus may carry higher viral loads than adults. To be sure, I am aware of the fact that for children, school is far more than an educational forum. For most, it fulfills vital social needs for peer interaction. And for too many, even for kids within my own district, school offers a respite from abuse, hunger, or an otherwise chaotic or uncertain home life. Taking away that refuge represents something much more dangerous than a delay or alteration in the educational process.
But for the millions engaging in virtual learning this semester, I am hopeful that parents, students, and teachers can view the situation in a light that extends beyond the obvious disruption to education as usual. I am hopeful that my own kids and others in their classes will cultivate valuable skills and thought patterns as they navigate the technological and social realities before them. After all, even before the pandemic changed so much about life in 2020, the world was becoming ever more connected, virtual, and off-site. There is a strong probability that the next generation will be learning or working remotely in their lifetimes. So at the start of another school year, one that none of us will soon forget, I commend staff members, teachers, school board members, students, and parents who are braving our new normal, and urge them to see the positive in this difficult situation.
Bob Grant
Editor-in-Chief