It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Friday, November 20, 2020
As COVID toll among Kenyan doctors jumps, one widow shares her grief Baz Ratner and Maggie Fick Thu, 19 November 2020, A Funeral for Doctor Alushula who died of COVID-19 in Khumusalaba village
By Baz Ratner and Maggie Fick
KHUMUSALABA, Kenya (Reuters) - When Daniel Alushula began gasping for air after contracting COVID-19 last month, all the intensive care beds in his home town hospital were taken and he had to travel around 50 km (30 miles) to secure one.
The 60-year-old orthopedic surgeon died a week later on Oct. 30, his family said, one of nine Kenyan doctors to have succumbed to the virus in the past four weeks, according to the Kenya Medical Practitioners, Pharmacists and Dentists Union.
He was active in the union's campaign to better protect doctors and their families from the risk of catching while at work, fellow medic Anthony Akoto said.
Four of the nine doctors who have fallen victim to the pandemic died over the past weekend, and the Union has threatened a national strike from Dec. 6 if the government fails to provide protective equipment and medical insurance for its members, and compensation for health workers who die from COVID-19.
"We are not going to be sacrificial lambs," its secretary-general, Chibanzi Mwachonda, told Reuters.
The Health Ministry did not respond to requests for comment.
Up to mid-October, COVID-19 had killed just one Kenyan doctor, as travel restrictions and mandatory mask wearing spared the country the worst of its first wave.
However, the disease has spread faster in the general population too since the government eased the curbs in late September, with compliance with mask wearing and social distancing also dropping.
As of Wednesday, the country had reported 1,313 deaths, about a quarter of which have occurred in November, and hospital beds are filling up across the country.
Before he died, Alushula tried to keep his colleagues' spirits up.
"No need to panic, daktari", Alushula wrote in a text message from his ICU bed to Akoto, a younger doctor he mentored at the hospital in the western district of Busia where they both worked. "You take care of the others, but I will pull through."
Akoto said Alushula's health insurance as a public doctor did not cover his COVID treatment, which his family had to pay for his treatment themselves. His wife and two children were also infected but recovered.
Alushula had not been treating COVID patients, his colleagues said, and it was unclear how he was infected.
At his funeral on Saturday, his wife Carolyne Alushula recalled his dedication. If he was called to an emergency while they were out in the car, she would often take a bus home so that he could drive a sick person to hospital.
"He treasured his calling more than anything else," she said.
(Reporting by Baz Ratner in Khumasalaba, Kenya and Maggie Fick; Editing by Katharine Houreld and John Stonestreet)
Covid-19 mink variants discovered in humans in seven countries
Denmark has already launched a nationwide cull of its farmed mink herd after concerns for vaccine efficacy
Danish farmers have until midnight on Thursday 19 November to cull all mink in the country. Photograph: Mads Claus Rasmussen/Ritzau Scanpix/AFP/Getty
Seven countries are now reporting mink-related Sars-CoV-2 mutations in humans, according to new scientific analysis.
The mutations are identified as Covid-19 mink variants as they have repeatedly been found in mink and now in humans as well.
Uncertainty around the implications of the discovery of a Covid-19 mink variant in humans led Denmark, the world’s largest mink fur producer, to launch a nationwide cull earlier this month.
The cull was sparked by research from Denmark’s public health body, the Statens Serum Institut (SSI), which showed that a mink variant called C5 was harder for antibodies to neutralise and posed a potential threat to vaccine efficacy. Denmark, the Netherlands, South Africa, Switzerland, the Faroe Islands, Russia and the US have all reported cases of mink-related mutations.
Despite a political backlash the cull has continued, and farmers have until midnight on Thursday to cull all mink in the country. However, the row over the cull has forced the resignation of the Danish agriculture minister, Mogens Jensen.
SSI director Kåre Mølbak has also said he would resign. It was the SSI’s findings on reduced antibody efficacy that led to the cull order. Mølbak told local media he is retiring because he is 65 and denied it was related to the mink cull.
Until now there had been no widespread reports of mink variants in humans outside Denmark. But scientists uploading virus sequencing and variant information to Gisaid, a global database initiative, said there have been signs of the mink variants around the world.
“We knew there were these mink variants in seven countries, but we only had about 20 genomes of each, which is very few. Then last week the Danes uploaded 6,000 genome sequences and with those we were able to identify 300 or more of the mink variant Y453F in viruses having infected humans in Denmark,” said University College London (UCL) Genetics Institute director Francois Balloux.
Asked about the implications of the findings, Balloux said it was an indication of the need to cull farmed mink. “A bigger host reservoir means more infections in humans. The main point here, I think, is that although the mutation might not be scary, there is still very good reason to get rid of the mink reservoir. We just don’t need it.” In Denmark, he added, they have a lot of mink, “over three times more than humans”. Denmark's mass mink cull illegal, PM admits as opposition mounts Read more
The prevalence of Danish mink-related mutations is evident in the Gisaid database. “Denmark has 329 F-variant sequences, which roughly maps to as many individuals, although there may be some duplicates,” said Prof Seshadri Vasan, who leads the dangerous pathogens team at Australia’s Commonwealth Scientific and Industrial Research Organisation (CSIRO) and analysed the database for the mink variants. “The Netherlands has six. South Africa and Switzerland have two each, while the Faroe Islands, Russia and Utah [US] have one each.”
Asked how the spread might have happened, Vasan said that given some of the human and mink F-variants were from samples collected in Denmark in June, it might be that “movement of people, animals or goods could have spread the F-variant to other countries”.
But, because the Gisaid database includes only patchy patient information and no travel history – and as some of the samples lack collection dates – he said it is impossible to say exactly how and when the spread took place, although local scientists might be better placed to understand.
Last month, Vasan and his team published a global template aimed at improving the collection and sharing of de-identified patient information in a bid to improve data quality.
Viruses are known to mutate, but variants alone are not necessarily a problem. Most importantly, said Prof Joanne Santini, a microbiologist at UCL, we still don’t know whether this mutation happened in mink or humans first.
In a joint email this week to the Guardian, Santini and UCL colleague Prof Sarah Edwards, a bioethicist, said the Sars-CoV-2 Y453F variant in the spike protein is “unlikely to pose any serious risk to the expected efficacy of current candidate vaccines, or itself pose a new public health threat” on its own.
If, however, the variant originated in mink and spread to humans, “then we would have to doubt our ability to manage outbreaks in otherwise seemingly contained farm animals once detected”.
Constant mutations could be a source of concern too. The email added that “multiple additional variants in the spike protein could indeed have concerning implications for how infectious the virus is to humans and also to animals”, potentially posing “new threats to the expected efficacy of our candidate vaccines”.
“The early observations by CSIRO scientists demonstrate the possible implications for the wider spread of Sars-CoV-2 variants between humans and animals,” she said.
Although Denmark is the only country to order a nationwide mink cull, others, including the Netherlands, Spain and, most recently, Greece, are killing mink with Covid-19. On Tuesday, Reuters reported mandatory mink testing had started in Poland, despite industry fears that tests could lead to a nationwide cull.
On the business side, the Danish cull has had immediate effects. Last week, Denmark’s breeder association and world’s largest fur auction house, Kopenhagen Fur, announced a “controlled shutdown” over the next three years, while Danish thinktank estimates put the cost of mink farm closures at about DKK3bn (£360m).
Two K-State studies focus on SARS-CoV-2 transmission in domestic cats, pigs
IMAGE: JÜRGEN A. RICHT, THE REGENTS DISTINGUISHED PROFESSOR AT KANSAS STATE UNIVERSITY IN THE COLLEGE OF VETERINARY MEDICINE, IS THE SENIOR AUTHOR ON TWO RECENTLY PUBLISHED STUDIES THAT FOCUS ON SARS-COV-2... view more
CREDIT: KANSAS STATE UNIVERSITY
MANHATTAN, KANSAS -- Two recently published studies from Kansas State University researchers and collaborators have led to two important findings related to the COVID-19 pandemic: Domestic cats can be asymptomatic carriers of SARS-CoV-2, but pigs are unlikely to be significant carriers of the virus. SARS-CoV-2 is the coronavirus responsible for COVID-19.
"Other research has shown that COVID-19-infected human patients are transmitting SARS-CoV-2 to cats; this includes domestic cats and even large cats, such as lions and tigers," said Jürgen A. Richt, the Regents distinguished professor at Kansas State University in the College of Veterinary Medicine. "Our findings are important because of the close association between humans and companion animals."
There are about 95 million house cats in the U.S. and about 60 million to 100 million feral cats, Richt said.
Richt is the senior author on the two recent collaborative publications in the journal Emerging Microbes & Infections: "SARS-CoV-2 infection, disease and transmission in domestic cats" and "Susceptibility of swine cells and domestic pigs to SARS-CoV-2."
Through their in-depth study at the K-State Biosecurity Research Institute, or BRI, at Pat Roberts Hall, the researchers studied susceptibility to infection, disease and transmission in domestic cats. They found that domestic cats may not have obvious clinical signs of SARS-CoV-2, but they still shed the virus through their nasal, oral and rectal cavities and can spread it efficiently to other cats within two days. Further research is needed to study whether domestic cats can spread the virus to other animals and humans.
"This efficient transmission between domestic cats indicates a significant animal and public health need to investigate a potential human-cat-human transmission chain," said Richt, who is also the director of the university's Center of Excellence for Emerging and Zoonotic Animal Diseases, known as CEEZAD, and the Center on Emerging and Zoonotic Infectious Diseases, known as CEZID.
For the study involving pigs, the researchers found that SARS-CoV-2-infected pigs are not susceptible to SARS-CoV-2 infection and do not appear to transmit the virus to contact animals.
"Pigs play an important role in U.S. agriculture, which made it important to determine the potential SARS-CoV-2 susceptibility in pigs," Richt said. "Our results show that pigs are unlikely to be significant carriers of SARS-CoV-2."
The BRI has provided the high-security laboratories for Richt and collaborators to study SARS-CoV-2. It is a biosafety level-3 and biosafety level-3 agriculture facility that houses important multidisciplinary research, training and educational programs on pathogens that affect animals, plants and insects, as well as food safety and security.
Richt and his collaborators plan further studies to understand SARS-CoV-2 transmission in cats and pigs. They also plan to study whether cats are immune to SARS-CoV-2 reinfection after they have recovered from a primary SARS-CoV-2 infection.
"This research is important for risk assessment, implementing mitigation strategies, addressing animal welfare issues, and to develop preclinical animal models for evaluating drug and vaccine candidates for COVID-19," Richt said.
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The research has involved other K-State researchers from the department of diagnostic medicine and pathobiology in the College of Veterinary Medicine: Natasha N. Gaudreault, Jessie D. Trujillo, David A. Meekins, Igor Morozov, Daniel W. Madden, Sabarish V. Indran, Dashzeveg Bold, Velmurugan Balaraman, Taeyong Kwon, Bianca L. Artiaga, Konner Cool, Wenjun Ma and Jamie Henningson, also director of the Kansas State Veterinary Diagnostic Laboratory.
Other researchers involved include Mariano Carossino and Udeni B. R. Balasuriya from Louisiana State University; William C. Wilson with the U.S, Department of Agriculture's Arthropod-Borne Animal Disease Research Unit; Adolfo García-Sastre with Icahn School of Medicine at Mount Sinai; and Heinz Feldmann with the National Institutes of Health's National Institute of Allergy and Infectious Diseases.
Getting it just right - the Goldilocks model of cancer
IMAGE: WNT SIGNALLING DAMPENS RAS-MAPK SIGNALLING, ENABLING CANCER CELLS TO GROW STEADILY INSTEAD OF HEADING TOWARDS THE PREMATURE AGEING THAT CAN BE CAUSED BY EXCESSIVE RAS-MAPK SIGNALLING. WHEN RESEARCHERS INHIBITED WNT... view more
CREDIT: DUKE-NUS MEDICAL SCHOOL
SINGAPORE, 20 November 2020 - Sometimes, too much of a good thing can turn out to be bad. This is certainly the case for the excessive cell growth found in cancer. But when cancers try to grow too fast, this excessive speed can cause a type of cellular ageing that actually results in arrested growth. Scientists at Duke-NUS Medical School have now discovered that a well-known signalling pathway helps cancers grow by blocking the pro-growth signals from a second major cancer pathway.
Inhibiting Wnt signalling with ETC-159 reactivates the hyperactive RAS-MAPK pathway, causing cells to led undergo senescence.Many cancers are driven by activating mutations in the RAS-MAPK signalling pathway which triggers a cascade of proteins that directs cells to grow, divide and migrate. Mutations in proteins involved in this cascade can turn on genes that make this process go into overdrive, causing cells to grow out of control and aggressively invade other parts of the body. However, too much RAS-MAPK signalling causes cancer cells to prematurely age, and eventually stop growing -- a process called cellular senescence.
Publishing in Cancer Research, the Duke-NUS research team found that another important and well-known biochemical pathway, the 'Wnt' (pronounced 'wint') signalling pathway, allows some cancers to grow by dampening RAS-MAPK signalling.
The team made the discovery while investigating how Wnt proteins regulate pancreatic cancers. Scientists have long observed that genetic mutations causing Wnt proteins to be hyperactive drive many common cancers. The long-held thinking had been that this is because Wnt signalling causes cells to grow too fast. The new findings suggest this idea needs re-evaluation.
By making RAS-MAPK signalling "not too hot and not too cold", Wnt signalling enables cancers to grow steadily instead of heading towards the premature ageing that can be caused by excessive RAS-MAPK signalling. These findings support a growing awareness that cancers need a "just-right" level of RAS-MAPK signalling. Disrupting modulating signals like Wnt can cause cancers to stop growing by forcing them to undergo cellular senescence, similar to just getting old.
Assistant Professor Babita Madan, from Duke-NUS Cancer and Stem Cell Biology (CSCB) Programme, a senior co-author of the study, explained, "Using an experimental drug, ETC-159 , to stop Wnts in multiple models of human pancreatic and colorectal cancer, we found that, unexpectedly, Wnt signalling turns off as many genes as it turns on."
Digging deeper, the team made the connection between Wnt signalling and the diminished activity of the RAS-MAPK pathway. Inhibiting Wnt signalling with ETC-159 and other anti-cancer drugs actually activated RAS-MAPK signalling, while inhibiting cancer growth at the same time.
"This makes sense; while activating mutations in the RAS-MAPK pathway are common in cancer, in isolation, they cause cells to stop growing by causing senescence, a form of ageing-induced arrested cell growth," said Professor David Virshup, Director of the CSCB Programme, and also a senior co-author of the study. (Prof Virshup's seminal research on Wnts led to the development of ETC-159.) "By reining in RAS-MAPK signalling, Wnt signalling achieves Goldilocks' goal of getting it not too hot, not too cold, but just right."
One implication of this research is that it opens up additional ways to attack cancers. The traditional way is to kill cancer cells, however this new study shows that stopping cancer cell growth can be achieved by inducing senescence.
"Cancer is the second leading cause of death globally, responsible for an estimated one in six deaths. In Singapore, cancer cases have been rising over the years, and the number of people living with cancer will continue to increase ," noted Professor Patrick Casey, Senior Vice Dean for Research at Duke-NUS. "Studies like these exemplify the importance of robust fundamental science research to guide new approaches and strategies that have the potential to make a major impact on disease."
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Breast cancer discovery could help stop disease's deadly spread
IMAGE: UVA'S SANCHITA BHATNAGAR, PHD, FOUND THAT THE BREAST CANCER ONCOGENE TRIM37 NOT ONLY CAUSES TRIPLE NEGATIVE BREAST CANCER TO SPREAD BUT ALSO MAKES IT RESISTANT TO CHEMOTHERAPY. view more
CREDIT: DAN ADDISON | UVA COMMUNICATIONS
University of Virginia Cancer Center researchers have identified a gene responsible for the spread of triple-negative breast cancer to other parts of the body - a process called metastasis - and developed a potential way to stop it.
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that accounts for 40,000 deaths in the United States annually. The majority of these deaths result from resistance to chemotherapy and subsequent aggressive metastases. So UVA researchers asked: What causes a primary tumor to become metastatic? This is an important question in cancer biology because patients with metastatic tumors have the highest death rate.
UVA's Sanchita Bhatnagar, PhD, and her team found that the breast cancer oncogene TRIM37 not only causes the cancer to spread but also makes it resistant to chemotherapy. A new approach she and her colleagues have developed could possibly address both, the researchers hope.
"Despite metastasis being the key reason for failure of cancer therapies, it remains poorly understood. We do not clearly understand what drives the metastatic growth in patients," said Bhatnagar, who was the first to identify TRIM37 as a breast cancer oncogene. "In general, several genes are altered during tumorigenesis. However, whether targeting the same genes will prevent metastatic transition remains to be addressed."
Promising research from Bhatnagar's team shows that targeting TRIM37 prevents metastatic lesions in mouse models. Those findings form the foundation of her lab's current work exploring the role of TRIM37 in racial disparities in triple negative breast cancer. Incidence of the disease is disproportionately higher in African-American women compared with other races, with a 5-year survival rate in African-American patients of only 14% compared with 36% in non-African-American women.
Targeting Triple-Negative Breast Cancer
Bhatnagar and UVA's Jogender Tushir-Singh, PhD, have developed a new approach to stop the effects of TRIM37 and, hopefully, prevent or significantly delay the spread of triple-negative breast cancer. This could also lower the disease's defenses against chemotherapy.
Blocking the gene could benefit approximately 80% of triple negative breast cancer patients, the researchers estimate.
Bhatnagar and Tushir-Singh's approach uses nanoparticles - microscopic balls of fat - to deliver treatment to block TRIM37. These nanoparticles are paired with specially engineered antibodies that bind to the cancerous cells but not to healthy cells. "As soon as the antibody finds the triple negative breast cancer cell, it binds to the receptor and is taken up by the cell," explained Tushir-Singh, of UVA's Department of Biochemistry and Molecular Genetics.
"It is a kiss of death," Bhatnagar said, "that selectively reduces the expression of TRIM37 in cancer cells and prevents the spread."
The approach could be used to deliver targeted treatments for many other cancers as well, the researchers report. "That would not only get the treatment where it needs to be but, hopefully, help prevent unwanted side effects. Besides preventing metastases, it adds selectivity," Bhatnagar said.
"A problem in the field is, how will you give [a nanoparticle treatment] to the patients? Most of these nanoparticles are cleared by the liver, so they never have a chance to really do their job," she said. "In this study, researchers bypassed this issue by delivering nanoparticles by nasal route, increasing the rate of uptake in the lungs - one of the most common metastatic target sites in TNBC patients."
The development of the new approach is in its early stages, but tests with lab mice have offered encouraging indications. "The lungs showed dramatic reduction in metastatic lesions after the treatment in comparison to the mice that received no treatment," Bhatnagar said.
Next Steps
To verify that TRIM37 targeting might offer a potential treatment approach, Bhatnagar teamed up with Tushir-Singh, her husband, to test it in the lab. "And we find that our targeted nanoparticles significantly reduce metastatic lesions in the lungs of spontaneous metastatic murine [mouse] models - both immune compromised and immune sufficient," she said. "This is an important proof-of-concept much needed for the bench-to-clinic transition of these important findings."
Clinically, most women in the early stages of breast cancer are treated with surgery, followed by radiation or chemotherapy. However, metastasis remains a challenging medical problem. Bhatnagar's research offers a potential way to target a driver of metastasis that she hopes will prevent or slow metastatic progression and improve overall survival.
Much more work needs to be done, but Bhatnagar's research is being noticed by pharmaceutical companies interested in exploring the approach's potential. "This is a delivery platform, not only for targeting our protein of interest but for many other chemotherapeutic drugs that can be packaged into the nanoparticles and selectively delivered," Bhatnagar said.
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Findings Published
The researchers have published their findings in the scientific journal Cancer Research. The research team consisted of Piotr Przanowski, Song Lou, Rachisan Djiake Tihagam, Tanmoy Mondal, Caroline Conlan, Gururaj Shivange, Ilyas Saltani, Chandrajeet Singh, Kun Xing, Benjamin B. Morris, Marty W. Mayo, Luis Teixeira, Jacqueline Lehmann-Che, Jogender Tushir-Singh and Sanchita Bhatnagar.
Bhatnagar, a Hartwell Investigator, is supported by the Department of Defense Breast Cancer Research Breakthrough Award (BC170197P1, BC190343P1) and Metavivor Translational Research Award. A provisional patent has been filed for the molecularly targeted nanoparticle design engineered by the Bhatnagar and Tushir-Singh laboratories.
IMAGE: IN GLYPHOSATE-SENSITIVE BACTERIA, THE EPSPS ENZYME IN THE SHIKIMATE PATHWAY IS BLOCKED BY GLYPHOSATE AND THE ESSENTIAL AROMATIC AMINO ACIDS ARE NOT PRODUCED. GLYPHOSATE-RESISTANT BACTERIA ARE NOT AFFECTED BY THE... view more
CREDIT: PERE PUIGBÒ
Glyphosate is the most commonly used broad-spectrum herbicide. Researchers from the University of Turku in Finland have developed a new bioinformatics tool to predict if a microbe, e.g. a human gut bacterium, is sensitive to glyphosate.
"Glyphosate targets an enzyme called EPSPS in the shikimate pathway. This enzyme is crucial to synthesizing three essential amino acids. Based on the structure of the EPSPS enzyme, we are able to classify 80-90% of microbial species into sensitive or resistant to glyphosate," says Docent Pere Puigbò, developer of the new bioinformatics tool.
Based on the analyses using the new bioinformatics tool, 54% of the human core gut bacterial species are potentially sensitive to glyphosate.
"This groundbreaking study provides tools for further studies to determine the actual impact of glyphosate on human and animal gut microbiota and thus to their health," explains Docent Marjo Helander.
Glyphosate is thought to be safe to use because shikimate pathway is found only in plants, fungi and bacteria. However, glyphosate may have a strong impact on bacterial species in the human microbiome, and several recent studies have shown that perturbations in the human gut microbiome are connected to many diseases. Therefore, the widespread use of glyphosate may have a strong effect on gut microbiomes as well as on human health.
The dominance of this herbicide in the pesticide market is mainly attributed to the use of transgenic crops, such as soy, corn and canola, which are often grown as glyphosate-resistant varieties outside Europe. In Europe, glyphosate is commonly used to desiccate cereal, bean and seed crops before harvest. It is also used to eradicate weeds prior to sowing in no-till cropping systems.
The risk to come across glyphosate residue in food that has been grown in Finland is small, because desiccation of the cereal fields by glyphosate is not allowed in Finland.
A rich and diverse microbial community is living in soil, on plant surfaces, and in animal guts. It is possible that even low glyphosate residue may indirectly affect pest and pathogen occurrence in these communities.
"In addition to bioinformatics, we need experimental research to study the effects of glyphosate on microbial communities in variable environments," Helander adds.
An international research team led by UCSF scientists has shown, for the first time, that gut immune cells travel to the brain during multiple sclerosis (MS) flare-ups in patients. These gut cells seem to be playing a protective role, helping drive MS symptoms back into remission.
Scientists know that in MS, other types of immune cells go haywire and attack myelin, crucial insulation material that helps nerve cells communicate with one another quickly and reliably. The resulting damage leads to periodic MS attacks that can leave patients struggling with vision loss, memory problems, pain and other symptoms. These "relapse" symptoms often subside on their own after days or weeks, but medical experts still don't have a good understanding of what flips the switch from flare-up to remission and back again.
The new findings, published November 20, 2020 in Science Immunology, suggest that an unexpected new player might help bring flare-ups under control: immune cells from the gut that express a type of antibody called IgA. In the gut, these cells serve as a critical first line of defense against foreign invaders and, scientists think, help keep the teeming bacteria of our gut microbiome from growing out of control. Recently, a UCSF-led international research team made the surprising discovery that, in animal models of MS, these gut immune cells leave the digestive system and travel to the brain where they appear to help cut inflammation.
"It was a very new idea," said Sergio Baranzini, PhD, a professor of neurology and member of the UCSF Weill Institute for Neurosciences, lead author on the new study. "Nobody thought to look for this type of immune cell."
Now the team, including scientists in Canada, Germany, Sweden and Switzerland, has gone a step further, finding traces of the IgA antibody in the cerebrospinal fluid of MS patients during flare-ups, but not when episodes are in remission. They also found signs of IgA-producing immune cells in donated postmortem brain tissue that had been damaged during MS attacks. The findings confirm for the first time that gut immune cells are involved in MS relapses in humans.
"Only at the time of an attack was there an increase in these cells and the antibodies they produce," Baranzini said. "That really caught our attention."
In the hopes of determining what these gut immune cells were doing in the brain, the team then looked to see what kinds of molecules the IgA antibody reacted to. Recent research has provided evidence that an unhealthy gut microbiome plays a role in MS, when certain potentially damaging species of bacteria proliferate. While the team found that IgA did not bind to myelin protein, it did bind to some of these harmful bacteria species, suggesting that, unlike other immune cells, which are known to cause damage in MS, IgA-expressing immune cells play a protective role, possibly chasing these harmful bacteria to the brain and mounting a defense against them there.
"This opens up a whole new line of research," said Anne-Katrin Pröbstel, MD, a former UCSF postdoctoral researcher, now at the University of Basel in Switzerland and first author on the paper. "I think it has huge potential for therapeutics."
Collaborations within the UCSF Benioff Center for Microbiome Medicine allowed researchers to work with the various bacteria thought to be hallmarks of the MS microbiome, and the work relied heavily on data and biological samples collected through the multidisciplinary UCSF EPIC Study, which has followed hundreds of MS patients over 16 years.
"I think UCSF is one of the only places where we could have done this, because of the access to patient samples that allow us to look at bacteria in the gut, immune cells from the blood, immune cells from the spinal fluid and brain tissue," said Pröbstel. "It's really a unique resource."
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See study online for a full list of authors, funding information, and relevant disclosures.
About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes UCSF Health, which comprises three top-ranked hospitals, as well as affiliations throughout the Bay Area. Learn more at ucsf.edu, or see our Fact Sheet.
A Basel-led international research team has discovered a connection between the intestinal flora and sites of inflammation in the central nervous system in multiple sclerosis. A specific class of immune cell plays a central role in this newly identified gut-brain axis. The discovery could pave the way for new treatments for MS that target the intestinal flora.
What do you do when your own immune system attacks your nervous system? Newer treatments for the autoimmune disease multiple sclerosis (MS) rely on removing specific immune cells (B cells) from the blood of patients. However, researchers at both the University of Basel and the University Hospital Basel discovered several years ago that it's better not to remove too broad a range of B cells, as this can aggravate the disease.
A new study in the journal Science Immunology sheds more light on this observation: an international team of researchers, led by Dr. Anne-Katrin Pröbstel at the University of Basel and University Hospital Basel, has discovered that specific B cells form a kind of bridge between the intestinal flora and the sites of inflammation in the central nervous system, exerting an anti-inflammatory effect.
"We knew from earlier studies that the composition of intestinal flora plays a role in MS. But how exactly intestinal bacteria and immune cells influence one another was previously unknown," explains Pröbstel, the study's lead author.
Immune cells for gut and brain
At the heart of the new study are IgA-producing B cells, or IgA B cells in short. Immunoglobulin A (IgA) is a class of antibodies that specializes in immune defense of mucous membranes; the IgA B cells are key to intestinal health.
By analyzing stool samples from MS patients and healthy people, the researchers discovered that MS patients have IgA B cells in their intestines that target in particular bacteria typical of MS - i.e. bacteria that are more common in MS sufferers.
In a next step, the researchers analyzed the role of these immune cells during acute flares of the illness in a total of 56 MS patients. They found that IgA B cells accumulated in the cerebrospinal fluid and brain tissue of MS patients with acute sites of inflammation. "Apparently, these immune cells migrate from the intestine to the inflammation sites in the central nervous system, where they release an anti-inflammatory messenger substance," says Pröbstel. "That could explain why the illness worsens if these immune cells are removed from the blood with medication."
Trigger still unknown
What exactly activates the IgA B cells as helpers against MS and triggers their migration from the intestine to the central nervous system is still being investigated. "If we find the trigger for that, we could use it to treat MS," says Pröbstel. For example, it may be conceivable to change the composition of the intestinal flora of MS sufferers in a targeted way in order to mobilize IgA B cells as helpers against inflammation in the nervous system.
In addition to the University of Basel, other participants in the study included the University of California San Francisco, the Technical University of Munich, the universities of Heidelberg, Umeå (Sweden) and Toronto (Canada), and the Max Planck Institute of Colloids and Interfaces in Potsdam. The study was funded among others by the National Multiple Sclerosis Society and the Swiss National Science Foundation.
IMAGE: FIGURE 1 FROM THE PAPER: EXAMPLES OF TWITTER CONVERSATIONS (REPLY TREES) WITH LABELED HATE (RED), COUNTER (BLUE), AND NEUTRAL SPEECH (WHITE). THE ROOT NODE IS SHOWN AS A LARGE SQUARE. view more
CREDIT: GARLAND ET AL, EMNLP 2020
The rise of online hate speech is a disturbing, growing trend in countries around the world, with serious psychological consequences and the potential to impact, and even contribute to, real-world violence. Citizen-generated counter speech may help discourage hateful online rhetoric, but it has been difficult to quantify and study. Until recently, studies have been limited to small-scale, hand-labeled endeavors.
A new paper published in the proceedings of the 2020 Conference on Empirical Methods in Natural Language Processing (EMNLP) offers a framework for studying the dynamics of online hate and counter speech. The paper offers the first large-scale classification of millions of such interactions on Twitter. The authors developed a learning algorithm to assess data from a unique situation on German Twitter, and the findings suggest that organized movements to counteract hate speech on social media are more effective than individuals striking out on their own.
"I've seen this big shift in civil discourse in the last two or three years towards being much more hateful and much more polarized," says Joshua Garland, a mathematician and Applied Complexity Fellow at the Santa Fe Institute. "So, for me, an interesting question was: what's an appropriate response when you're being cyber-bullied or when you're receiving hate speech online? Do you respond? Do you try to get your friends to help protect you? Do you just block the person?"
To study such questions scientifically, researchers must first have access to a wealth of real-world data on both hate speech and counter-speech, and the ability to distinguish between the two. That data existed, and Garland and collaborator Keyan Ghazi-Zahedi at the Max Planck Institute in Germany found it in a five-year interaction that played out over German Twitter: As an alt-right group took to the platform with hate speech, an organized movement rose up to counter it.
"The beauty of these two groups is they were self-labeling," explains Mirta Galesic, the team's social scientist and a professor of human social dynamics at SFI. She says researchers who study counter-speech usually have to employ hundreds of students to hand-code thousands of posts. But Garland and Ghazi-Zahedi were able to input the self-labeled posts into a machine-learning algorithm to automate large swaths of the classification. The team also relied on 20-30 human coders to check that the machine classifications matched up with intuition about what registers as hate and counter-speech.
The result was a dataset of unprecedented size that allows the researchers to analyze not just isolated instances of hate and counter speech, but also compare long-running interactions between the two.
The team collected one dataset of millions of tweets posted by members of the two groups, using these self-identified tweets to train their classification algorithm to recognize hate and counter speech. Then, they applied their algorithm to study the dynamics of some 200,000 conversations that occurred between 2013 and 2018. The authors plan to soon publish a follow-up paper analyzing the dynamics revealed by their algorithm.
"Now we can resolve a massive data set from 2016 to 2018 to see how the proportion of hate and counter-speech changed over time, who gets more likes, who is retweeted, and how they replied to each other" Galesic says.
The quantity of data, a tremendous boon, also makes it "incredibly complex," Garland notes. The researchers are in the process of comparing tactics for both groups and pursuing broader questions such as whether certain counter-speech strategies are more effective than others.
"What I'm hoping is that we can come up with a rigorous social theory that tells people how to counter hate in a productive way that's non-polarizing," Garland says, "and bring the Internet back to civil discourse."
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Dogmatic people seek less information even when uncertain
People who are dogmatic about their views seek less information and make less accurate judgements as a result, even on simple matters unrelated to politics, according to a study led by UCL and Max Planck Institute for Biological Cybernetics researchers.
The researchers say their findings, published in PNAS, point to differences in thinking patterns that lead people to hold rigid opinions.
First author Lion Schulz, a PhD candidate at the Max Planck Institute in Germany who began the research while at UCL, said: "Anecdotally, it seems that dogmatic people are less interested in information that might change their mind. However, it was unclear if this is because a specific opinion is of high importance to them or if more fundamental processes are at play that transcend specific opinions."
Dogmatic people are characterised by a belief that their worldview reflects an absolute truth and are often resistant to change their mind, for example when it comes to partisan issues. This tendency can have societal impacts by polarising political, scientific and religious debates. However, the cognitive drivers of dogmatism are still poorly understood.
To investigate this, the researchers asked over 700 people to perform a simple decision-making task. Participants saw two boxes with flickering dots and had to decide which box contained more of the dots. Critically, after the participants had made an initial choice, the researchers gave them the chance to view another, clearer version of the boxes. They then made a final decision.
Schulz explained: "This mirrors many real-life situations - for example, when we hear a rumour but aren't sure if it's true. Do we share it, or do we check a credible source beforehand?"
Joint first author, Dr Max Rollwage (Wellcome Centre for Human Neuroimaging at UCL and Max Planck UCL Centre for Computational Psychiatry & Ageing Research) said: "By using simple tasks, we were able to minimise motivational or social influences and pin down drivers of altered evidence processing that contribute to dogmatic beliefs."
The task was followed by a comprehensive set of questionnaires that allowed the researchers to measure participants' political orientation and levels of dogmatism.
Dogmatic individuals and moderates did not differ in their accuracy or confidence of their decisions. However, the researchers found that more dogmatic participants were more likely to decline the helpful additional information.
The differences between more and less dogmatic participants were especially large when participants had little confidence in a decision. Senior author Dr Steve Fleming (Wellcome Centre for Human Neuroimaging at UCL, Max Planck UCL Centre for Computational Psychiatry & Ageing Research and UCL Experimental Psychology) said: "Previous work has found that there is a close link between how confident we feel and whether or not we seek out new information. In the current study we found that this link was weaker in more dogmatic individuals."
In general, the reduced search was detrimental, with more dogmatic people being less accurate in their final judgements.
Dr Fleming added: "It is striking that we could detect links between dogmatism about issues such as politics, and information-seeking in a simple online game. This tells us that real-world dogmatism isn't just a feature of specific groups or opinions but may be associated with more fundamental cognitive processes."
The study highlights that simply having corrective information available does not necessarily mean people will consume it.
Schulz said: "This is particularly relevant today. We have never been so free to decide if we have enough evidence about something or whether we should seek out further information from a reliable source before believing it.
"It is also important to stress that the differences between more and less dogmatic people were subtle, and we don't know yet how they would manifest when considering real-world information such as news about political parties. In the end, it's a cautionary tale, whether we think of ourselves as dogmatic or not: when uncertain, it might be wise to check the information again."
The researchers are now trying to further unravel the underlying cognitive algorithms which trigger people to search for further information in situations of uncertainty.
Simple, no-cost ways to help the public care for the commons
Researchers from University of Wisconsin-Madison, New York Institute of Technology, University of Iowa, and Cornell University published a new paper in the Journal of Marketing that examines whether it is possible to make people feel as if the property is theirs--a feeling known as psychological ownership--and how this affects their stewardship behaviors.
The study, forthcoming in the Journal of Marketing, is titled "Caring for the Commons: Using Psychological Ownership to Enhance Stewardship Behavior for Public Goods" and is authored by Joann Peck, Colleen Kirk, Andrea Luangrath, and Suzanne Shu.
Maintaining the natural environment is a pressing issue. The intentional care of public goods, such as publicly owned parks, waterways, drinking water, and air quality, has become increasingly difficult. For example, for public parks, it has become more challenging during the pandemic as park services are reduced while the number of people spending time outside has increased. It is widely acknowledged that property that is publicly, versus individually, owned tends to be more neglected by its users - a phenomenon known in economics as the tragedy of the commons.
The most extreme solution to a tragedy of the commons problem is to convert common property into private property so that a single owner has responsibility for its care. As Peck explains, "We wondered whether it is possible to instead make people feel as if the property is theirs--a feeling known as psychological ownership--without any change to legal ownership. The hypothesis is that people who feel as if they own a public resource might be more likely to engage in stewardship behaviors." Leveraging psychological ownership, the researchers developed a series of actionable interventions that managers of public goods can implement to elicit feelings of ownership in users. Four experiments tested this hypothesis.
The first study was at a public lake with kayakers. Floating trash was set in the water where kayakers would see it. As visitors rented kayaks, half were asked to create a nickname for the lake before entering the water. Using binoculars, the researchers observed whether the kayakers tried to pick up the planted trash. Kayakers who gave the lake a nickname felt more ownership of the lake. Most importantly, they were more than five times as likely to try to pick up the planted trash (41% vs. 7% of the other kayakers).
In the second study, participants imagined taking a walk in a park. They were shown a sign at the park entrance that said either "Welcome to the Park" or "Welcome to YOUR Park." Participants who saw the "YOUR park" sign felt more ownership and responsibility for the park, were more likely to pick up trash, and would donate 34% more to the park ($32.35 vs. $24.08).
The third study tested yet a different way to elicit psychological ownership to see if it could increase actual donations. This study involved cross-country ski renters at a state park. As they rented equipment, they received a map. Half of them were asked to plan their route on the map in advance. The prediction was that this investment of time might increase the skiers' psychological ownership of the park and thus increase their donations through the addition of $1.00 to the rental fee. As expected, skiers who planned their routes and therefore felt more ownership donated to the park 2.5 times more often than those who did not plan their routes. They also reported being more likely to volunteer for the park, to donate in the future, and to promote the park on social media.
The fourth study explored whether managers of public goods may be unintentionally discouraging stewardship behaviors. Many parks tout their attendance numbers, but the intuition was that an attendance sign with a large number of people on it might diffuse users' feelings of responsibility. Research participants imagined they were visiting a park and saw either a "the park" or "YOUR park" welcome sign. Then half of them imagined seeing an attendance sign that read "This week, you are visitor #22,452". (Many U.S. parks have over a million visitors annually, so we designed an attendance sign that included an appropriately large number.) Participants were given money for participating, but also had the option to use some of that money for an anonymous donation to the park. As in the prior studies, individuals who felt more ownership of the park donated more to the park. They were also more likely to say that they would volunteer to help the park, including picking up trash. However, these effects were reduced when participants imagined the attendance sign, which possibly suggested the feeling that these other people would take responsibility for the park.
"This research has implications for consumers, organizations caring for public resources, policy makers, and for-profit companies by demonstrating that simple interventions based on increasing psychological ownership can enhance stewardship of public goods. The actionable interventions we designed and tested to increase psychological ownership are inexpensive, novel, and flexible solutions that successfully motivate individual stewardship behaviors" says Luangrath. By fostering visitors' individual feelings of ownership of a public resource, visitors will feel more responsible for it, take better care of it, and donate more time and money for its benefit.
The Journal of Marketing develops and disseminates knowledge about real-world marketing questions useful to scholars, educators, managers, policy makers, consumers, and other societal stakeholders around the world. Published by the American Marketing Association since its founding in 1936, JM has played a significant role in shaping the content and boundaries of the marketing discipline. Christine Moorman (T. Austin Finch, Sr. Professor of Business Administration at the Fuqua School of Business, Duke University) serves as the current Editor in Chief.
As the largest chapter-based marketing association in the world, the AMA is trusted by marketing and sales professionals to help them discover what's coming next in the industry. The AMA has a community of local chapters in more than 70 cities and 350 college campuses throughout North America. The AMA is home to award-winning content, PCM® professional certification, premiere academic journals, and industry-leading training events and conferences.
