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Category Archives: Kansas Stem Cells

Human cells in a rat’s brain could shed light on autism and ADHD – Kansas Public Radio

Posted: October 13, 2022 at 1:45 am

Scientists have demonstrated a new way to study conditions like autism spectrum disorder, ADHD, and schizophrenia.

The approach involves transplanting a cluster of living human brain cells from a dish in the lab to the brain of a newborn rat, a team from Stanford University reports in the journal Nature.

The cluster, known as a brain organoid, then continues to develop in ways that mimic a human brain and may allow scientists to see what goes wrong in a range of neuropsychiatric disorders.

"It's definitely a step forward," says Paola Arlotta, a prominent brain organoid researcher at Harvard University who was not involved in the study. "The ultimate goal of this work is to begin to understand features of complex diseases like schizophrenia, autism spectrum disorder, bipolar disorder."

But the advance is likely to make some people uneasy, says bioethicist Insoo Hyun, director of life sciences at the Museum of Science in Boston and an affiliate of the Harvard Medical School Center for Bioethics.

"There is a tendency for people to assume that when you transfer the biomaterials from one species into another, you transfer the essence of that animal into the other," Hyun says, adding that even the most advanced brain organoids are still very rudimentary versions of a human brain.

The success in transplanting human brain organoids into a living animal appears to remove a major barrier to using them as models of human disease. It also represents the culmination of seven years of work overseen by Dr. Sergiu Pasca, a professor of psychiatry and behavioral sciences at Stanford.

Human brain organoids are made from pluripotent stem cells, which can be coaxed into becoming various types of brain cells. These cells are grown in a rotating container known as a bioreactor, which allows the cells to spontaneously form brain-like spheres about the size of a small pea.

But after a few months, the lab-grown organoids stop developing, says Pasca, whose lab at Stanford devised the transplant technique. Individual neurons in the cluster remain relatively small, he says, and make relatively few connections.

"No matter how long we keep them in a dish, they still do not become as complex as human neurons would be in an actual human brain," Pasca says. That may be one reason organoids have yet to reveal much about the origins of complex neuropsychiatric disorders, he says.

So Pasca's team set out to find an environment for the organoids that would allow them to continue growing and maturing. They found one in the brains of newborn rats.

"We discovered that the [organoid] grows, over the span of a few months, about nine times in volume," Pasca says. "In the end it covers roughly about a third of a rat's hemisphere."

The transplanted cells don't seem to cause problems for the rats, who behave normally as they grow, Pasca says.

"The rat tissue is just pushed aside," he says. "But now you also have a group of human cells that are integrating into the circuitry."

The human cells begin to make connections with rat cells. Meanwhile, the rat's blood vessels begin to supply the human cells with oxygen and nutrients.

Pasca's team placed each organoid in an area of the rat brain that processes sensory information. After a few months, the team did an experiment that suggested the human cells were reacting to whatever the rat was sensing.

"When you stimulate the whiskers of the rat, the majority of human neurons are engaged in an electrical activity that follows that stimulation," Pasca says.

Another experiment suggests the human cells could even influence a rat's behavior.

The team trained rats to associate stimulation of their human cells with a reward a drink of water. Eventually, the rats began to seek water whenever the human cells were stimulated.

In a final experiment, Pasca's team set out to show how transplanted organoids could help identify the brain changes associated with a specific human disorder. They chose Timothy Syndrome, a very rare genetic disorder that affects brain development in ways that can cause symptoms of autism spectrum disorder.

The team compared organoids made from the stem cells of healthy people with organoids made from the stem cells of patients with the syndrome. In the lab, the cell clusters looked the same.

"But once we transplanted and we looked 250 days later, we discovered that while control cells grew dramatically, patient cells failed to do so," Pasca says.

A better model, with ethical concerns

The experiments show that Pasca's team has developed a better model for studying human brain disorders, Arlotta says.

The key seems to be providing the transplanted organoids with sensory information that they don't get growing in a dish, she says, noting that an infant's brain needs this sort of stimulation to develop normally.

"It's the stuff that we get after we are born," she says, "especially when we begin to experience the world and hear sound, see light, and so on."

But as brain organoids become more like actual human brains, scientists will have to consider the ethical and societal implications of this research, Arlotta says.

"We need to be able to watch it, consider it, discuss it and stop it if we think we think one day we are at the point where we shouldn't progress," she says. "I think we are far, far away from that point right now."

Even the most advanced brain organoids have nothing even remotely like the capabilities of a human brain, says Hyun, who posted a video conversation he had with Pasca to coincide with the publication of the new study.

Yet many ethical discussions have focused on the possibility that an organoid could attain human-like consciousness.

"I think that's a mistake," Hyun says. "We don't exactly know what we mean by 'human-like consciousness,' and the nearer issue, the more important issue, is the well-being of the animals used in the research."

He says that wasn't a problem in the Pasca lab's experiments because the organoids didn't seem to harm the animals or change their behavior.

If human brain organoids are grown in larger, more complex animal brains, Hyun says, the cell clusters might develop in ways that cause the animals to suffer.

"What I'm concerned about," he says, "is what's next."

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California is poised to phase out sales of new gas-powered cars – Kansas Public Radio

Posted: August 30, 2022 at 2:06 am

SACRAMENTO, Calif. California is poised to set a 2035 deadline for all new cars, trucks and SUVs sold in the state to be powered by electricity or hydrogen, an ambitious step that will reshape the U.S. car market by speeding the transition to more climate-friendly vehicles.

The California Air Resources Board will vote Thursday on the policy, which sets the most aggressive roadmap in the nation for moving away from gas-powered cars. It doesn't eliminate such vehicles, however.

People can continue driving gas-fueled vehicles and purchasing used ones after 2035. The plan also allows for one-fifth of sales after 2035 to be plug-in hybrids that can run on batteries and gas.

But it sets a course for ultimately ending the era of filling up at the local gas station. The switch from gas to electric cars will drastically reduce emissions and air pollutants. The transition may be painful in parts of the state that are still dominated by oil; California remains the seventh-largest oil producing state, though its output it falling as the state pushes forward with its climate goals.

"The climate crisis is solvable if we focus on the big, bold steps necessary to stem the tide of carbon pollution," Democratic Gov. Gavin Newsom said Wednesday. He announced the 2035 goal two years ago and regulators have spent the time since then working out the details of what Newsom termed "the action we must take if we're serious about leaving this planet better off for future generations."

There are practical hurdles to overcome to reach the goal, notably enough reliable power and charging stations. California now has about 80,000 stations in public places, far short of the 250,000 it wants by 2025. The Alliance for Automotive Innovation, which represents many major car makers, flagged the lack of infrastructure, access to materials needed to make batteries, and supply chain issues among the challenges to meeting the state's timeline.

"These are complex, intertwined and global issues well beyond the control of either (the California Air Resources Board) or the auto industry," John Bozella, the group's president, said in a statement.

Though the state makes up 10% of the U.S. car market, it's home to 43% of the nation's 2.6 million registered plug-in vehicles, according to the air board.

California climate officials say the state's new policy will be the world's most ambitious because it sets clear benchmarks for ramping up electric vehicle sales over the next dozen years. By 2026, for example, one-third of new cars sold must be electric. About 16% of cars sold in California in the first three months of this year were electric.

The European Parliament in June backed a plan to effectively prohibit the sale of gas and diesel cars in the 27-nation bloc by 2035, and Canada has mandated the sale of zero-emission cars by the same year. The Chinese province of Hainan said this week it would do the same by 2030.

In the U.S., Massachusetts, Washington and New York are among states that have set goals to transform their car markets or have already committed to following California's new rules.

California has historically been granted permission by the U.S. Environmental Protection agency to set its own tailpipe emissions rules for cars, and 17 other states follow some or all of its policies.

The new electric vehicle rules will also require federal approval, which is considered likely with President Joe Biden in the White House. A future Republican president, though, could challenge California's authority to set its own car standards, as the Trump administration did.

Indeed, the new commitment comes as California works to maintain reliable electricity while it moves away from gas-fired power plants in favor of solar, wind and other cleaner sources of energy. Earlier this year, top energy officials warned the state could run out of power during the hottest days of summer, which happened briefly in August 2020.

That hasn't happened yet this year. But Newsom is pushing to keep open the state's last-remaining nuclear plant beyond its planned closer in 2025, and the state may turn to diesel generators or natural gas plants as a backup when the grid is strained.

Adding more car chargers will put a higher demand on the energy grid.

Ensuring access to charging stations is also key to ramping up electric vehicle sales. The infrastructure bill passed by Congress last year provides $5 billion for states to build charges every 50 miles (80 kilometers) along interstate highways. Newsom, meanwhile, has pledged to spend billions to boost zero-emission vehicle sales, including by adding chargers in low-income neighborhoods.

Driving an electric vehicle long distances today, even in California, requires careful planning about where to stop and charge, said Mary Nichols, former chair of the California Air Resources Board. The money from the state and federal government will go along way to boosting that infrastructure and making electric cars a more convenient option, she said.

"This is going to be a transformative process and the mandate for vehicle sales is only one piece of it," she said.

Though hydrogen is a fuel option under the new regulations, cars that run on fuel-cells have made up less than 1% of car sales in recent years.

Both the state and government have rebates for thousands of dollars to offset the cost of buying electric cars, and the rules have incentives for car makers to make used electric vehicles available to low- and middle-income people. Over the past 12 years, California has provided more than $1 billion in rebates for the sale of 478,000 electric, plug-in or hybrid vehicles, according to the air board.

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Doctors Transplant Kidneys to Children Without Need for Immune …

Posted: July 11, 2022 at 2:25 am

THURSDAY, June 16, 2022 (HealthDay News) -- Researchers have figured out a way to safely give children a donor kidney without the need for immune-suppressing drugs -- an advance they hope to expand to many more kidney transplant patients in coming years.

Reporting in the June 15 issue of the New England Journal of Medicine, doctors at Stanford University describe the first three children to be treated with the new approach. It involved giving them not only a new kidney, but a new immune system -- both donated from a parent.

All three children now have normal kidney function, and are free of the anti-rejection drugs that transplant recipients normally have to take every day for the rest of their lives.

Much research remains before the approach can be widely offered, and experts cautioned that the three children in these cases had a rare genetic condition causing their kidney disease.

"This is a great outcome for these children," said Dr. Bradley Warady, director of pediatric nephrology at Children's Mercy Kansas City, in Missouri. "But we can't extrapolate this to all children who need a kidney transplant."

That caveat made, "there's cautious optimism this could become a more widespread procedure," said Warady, who is also on the board of directors for the National Kidney Foundation.

Lead researcher Dr. Alice Bertaina said the findings show a "holy grail" of transplant medicine is achievable.

"The most important thing is, we've shown this is possible," said Bertaina, an associate professor of pediatrics at Stanford.

Freeing kidney transplant recipients from anti-rejection drugs would be a huge advance, both doctors said. Lifelong immune suppression comes with a host of consequences, including heightened risks of serious infections and cancer, as well as conditions like diabetes and high blood pressure.

Dr. Eliza Blanchette, a pediatric nephrologist at Children's Hospital Colorado, pointed to another benefit of negating the need for anti-rejection drugs: Over time, they can actually damage the kidney they are designed to protect. So it's possible that freeing patients from the drugs could prolong the life of a donor kidney.

For years, researchers have sought a way to induce "immune tolerance" for donor organs, so that a lifetime of anti-rejection drugs is unnecessary. One approach is through a stem cell transplant from the organ donor.

Stem cells are primitive cells that give rise to mature cells, including those of the immune system. So, a stem cell transplant from an organ donor essentially provides the recipient with a new immune system that should recognize the donor organ and leave it unscathed.

The problem is that new immune system can also attack the recipient's body, causing a potentially fatal reaction called graft-versus-host disease (GVHD).

"It's been thought that the risk was too high," Bertaina said.

But she and her colleagues developed a protocol to minimize the risks, by refining how the donor stem cells are processed: They deplete the transplant of the particular cells, called alpha-beta T-cells, which cause GVHD.

The three children in the current report all received stem cells from their kidney-donor parent, and then five to 10 months later received the kidney itself. One child did develop mild GVHD, but it was managed with medication.

At this point, all three children have been living with fully functioning kidneys for 22 to 34 months -- without immune-suppressing drugs.

Jessica and Kyle Davenport of Muscle Shoals, Ala., are the parents of two of the children. Jessica was the donor for her 8-year-old son Kruz, while his 7-year-old sister, Paizlee, received transplants from Kyle.

"They've healed and recovered, and are doing things we never thought would be possible," Jessica Davenport said in a Stanford news release.

A major caveat is that all three kids have a rare genetic disorder called Schimke immuno-osseous dysplasia (SIOD). Along with kidney disease, SIOD causes short stature, immune system deficiencies and other problems.

Bertaina said the immune deficiencies seen in SIOD may actually be one reason the transplant approach worked so well for these kids.

Far more often, Warady said, pediatric kidney disease is caused by a birth defect, in children with normal immune function.

"We need more research to see if this is effective for children with an intact immune system," he said.

Blanchette also stressed that the effectiveness for children with normal immune function is not yet known.

Bertaina is hopeful this report will spur additional medical centers to do that kind of research. The Stanford team has already expanded the approach to other patient groups, including children whose bodies rejected a prior kidney transplant.

Those patients, Bertaina said, are generally "hypersensitized," and likely to reject a repeat transplant. So giving them a new immune system first might surmount that obstacle.

The ultimate hope, Bertaina said, is to expand the procedure to children, and adults, with a range of underlying causes for their kidney disease.

At this point, it requires a living donor who is a genetic half-match; for an adult, that could be a sibling or child, Bertaina noted. But the researchers are also hoping to adapt the protocol, to even include transplants from deceased donors.

More information

The Nemours Foundation has more on pediatric kidney disease.

SOURCES: Alice Bertaina, MD, PhD, associate professor, pediatrics, Stanford University School of Medicine, Stanford, Calif.; Bradley Warady, MD, member, board of directors, National Kidney Foundation, New York City, and director, pediatric nephrology/dialysis and transplantation, Children's Mercy Kansas City, Kansas City, Mo.; Eliza Blanchette, MD, pediatric nephrologist, Children's Hospital Colorado; Stanford University, news release, June 15, 2022; New England Journal of Medicine, June 16, 2022

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The Future of Parkinson Disease Therapies and the Challenges With Stem Cell Therapies – Neurology Live

Posted: June 22, 2022 at 2:49 am

The future of therapeutics for Parkinson disease (PD) appears to be bright, with the pipeline of clinical development featuring a vast number of investigational and varied approaches to treating the condition. This is notable because although levodopaa gold standard therapyhas provided many patients with relief from PD symptoms, there are still limitations to its abilities, and there are several needs that remain unaddressed.

In a presentation given by Rajesh Pahwa, MD, FANA, FAAN, on these emerging therapies at the2022 Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congressin Washington, DC, June 17-19, four specific therapies on the horizon were highlighted that might be able to address, at least in part, some of the shortcomings of the available options.1 Pahwa, the Laverne and Joyce Rider Professor of Neurology; chief, Parkinsons Disease and Movement Disorders Division; and director, Parkinsons Foundation Center of Excellence, University of Kansas Medical Center, shared that IPX-203, apomorphine subcutaneous infusion, continuous foslevodopa/foscarbidopa infusion (also known as ABBV-591), and continuous subcutaneous liquid levodopa/carbidopa (also known as ND0612) could all enter the market within the next couple years.

If I were to predict, I would say the next four of them would definitely be in the market in the next 3 to 4 years, Pahwa said. We have had levodopa which is the gold standard for the treatment of Parkinson disease. We have had different extended forms of levodopawe had the sustained release carbidopa-levodopa that came out 30 years ago. We had the extended-release capsules that came out, about 4 to 5 years ago now. The next generation, so to speak, is IPX-203.

He said that likely, the next therapy that will become available will be subcutaneous apomorphine infusion, closely followed by foslevodopa/foscarbidopa, and then IPX-203. The Neuroderm subcutaneous liquid levodopa [ND0612] will be another few years later. The rest of themwe do not know where they'll end up with phase 3 studies, he said.

The thing is, we still don't have that perfect carbidopa-levodopa where we can say OK, we have reached the stage that this is the best one out there. But every extended-release formulation, we have made some degree of improvement over the past. The extended-release capsules were better than the sustained release because we could get immediate action. And the same thing, I think, with IPX-203. We will, hopefully, have a better improvement than we saw with the previous one, he continued.

After running through the available clinical data on these therapies, Pahwa began to look further into the future of treatment. Touching briefly on the gene therapies that have been assessedmostly unsuccessfullyin PD, he then turned to stem cell-based therapies. Speaking to the hope that patients often carry when talking about the potential of stem cell approaches, he shared that this approach can often come with difficulties, and the progress has been slow.

READ MORE: The Importance of Treatment Nuance and Novel Options in Treating Parkinson Disease

We are very early in the journey of stem cell therapies. The challenges with Parkinson are multiple. You have to figure out the source of this stem cell, the quality of stem cell, age of the patient, stage of the patient, surgical techniques used, the need to use immunosuppression therapy or not use immunosuppression therapy, Pahwa explained. We are looking at a lot of challenges that we have not completely eliminated when we talk about stem cells. But like I said, every patient really feels that the stem cell is going to be an answer to their Parkinson's disease. The challenge is, as far as being a clinician is that Parkinson's is a progressive disorder that affects multiple areas in the brain. Using stem cell therapy, can we stop this progression? Can we actually slow down the disease or cure it? Or is it really going to only focus on dopaminergic replacement? And I think those are our challenges.

These challenges as well as the promises, he explained, can also be unique to each source of stem cells that is taken with this approach. For fetal ventral mesencephalic cells or embryonic stem cells, there are a few trials ongoingthe TRANSEURO (NCT01898390), STEM-PD (NCT02452723), and NYSTEM (NCT03119636), specificallyand there have been positives with these cells, including good long-term graft survival and their indefinite expandability. But they do carry ethical concerns and can be both unpredictable and limited in terms of their supply. Additionally, tissue rejection and tumorigenesis are possible risks.

Induced pluripotent stem cells are another approach in an ongoing trial at the Center for iPS Cell Research and Application, in Kyoto, Japan. These cells, similar to the aforementioned ones, also come with the benefit of indefinite expandability, and unlike the prior mentioned, have an easily accessible source and lack the need for immunosuppressive therapy. Although, they have a high operative cost, can be time consuming to develop, and require complex procedures.

The final option, neural progenitor cells, are also being assessed in two clinical trials (NCT03309514 and NCT01329926), and offer an easy expansion and differentiation protocol, as well as a large quantity source and multipotency. But, again, they carry risks such as low graft survivability and limited proliferation, and they require invasive tissue collection.

People are surprised that we are so slow with stem cells, Pahwa said. Seven years ago, I used to say, Oh, it's going to be 5 to 10 years, and everyone was led to believe that it was all the federal governments fault that we were going so slow. But really, it takes a long time, looking at the safety of it, because all you need is one patient who have a significant complication, and this is going to be put on the backburner for a long time.

Pahwa stressed the importance of being honest with patients about the progress being made in this area, given the significant interest from the general population in stem cell approaches. He warned about patients seeking out unapproved, unregulated treatment by either traveling out of the United States, or within.

What I tell my patients is don't spend the money because a lot of people out there [are selling this idea], not only if you're talking about going to a different country, even in the US, he said. I have a patient who was walking and doing well, who had stem cells injected in her spine, and could not walk after that. It is very likely she had, some form of fibrosing meningitis or something that that affected her gait significantly. Not only there is no efficacy data, there is no safety data. So, I strongly try to discourage my patients.

But the challenge is, people who are interested in stem cells, they often don't believe you, they want to go because the person who's doing the stem cells is doing a very good job selling this product for them. I don't know how to say we can stop this from happening, and that's why I always talk about how there are very few studies going on, Pahwa said.

Click here for more coverage of ATMRD 2022.

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Chemical Markers That May Unlock Future Therapeutic Uses of mRNA – Lab Manager Magazine

Posted: May 2, 2022 at 1:56 am

In recent years, messenger RNA, DNAs close cousin in lifes complex process of going from a string of genetic blueprints to fully functioning organism, has received intense scrutiny in the scientific and medical community for the role it can play in creating next-generation vaccines, cancer treatments, and stem cell therapies addressing a myriad of previously incurable diseases. The previously obscure topic of mRNA became a nearly universal household utterance following the rush to discover a type of vaccine that could prevent COVID-19 related fatalities. The scientific communitys herculean effort did result in Pfizers mRNA COVID-19 vaccine, and products with similar mechanisms of action closely follow from other US and global pharmaceutical companies.

An international research team led by Professor Katsura Asano of Hiroshima Universitys Graduate School of Integrated Sciences for Life in Japan, and also of Kansas State University in the US, set out to find new ways to artificially induce mRNA to respond in ways that could eventually lead to therapeutic outcomes, expanding on the success of the mRNA-based COVID-19 vaccines and opening up new possibilities across a host of possible genetic therapies.

Asano and his research team paid attention to a biochemical process termed chemical modification that adds a chemical mark to RNA bases, corresponding to a genetic letter of lifes blueprint, and identified such chemical marks that both speed up and slow down action in the beginnings of the chemical zippers involved in generating gene-specified proteins. They published their findings in Science Advances.

In animals, including humans, mRNA is called to action in the protein production process with a signal called the AUG Start Codon, a universal code for the genetic zipper of RNA. The compound that AUG makes up is an amino acid called methionine, one of the twenty building blocks of protein molecules. Other RNA codons such as GUG (amino acid Valine), UUG (amino acid Leucine), and CUG (also Leucine) are generally considered non-start codons, meaning theyre less likely to represent the beginning of a gene translation. Instead, they appear in the middle of protein coding region that is meant to unzip the genetic blueprint and produce a given protein.

Few other codons than AUG are known to be able to activate mRNA in the way AUG does. But in setting out to change that, Asano and his team set out to test common RNA chemical modifications, evaluating their effects on different types of rare start codons initiating the translation process. To do so, they used their previous discovery that GUG, UUG, and CUG codons that are different by one letter from AUG, are converted to a reasonably strong start codon specifying methionine through attaching the optimum RNA sequence for initiating their translation event in animals. Their study design pitted a dozen RNA sequences, derived from these sequences, for expressing green fluorescent proteins through various non-AUG start codons at various efficiencies. To accurately evaluate GFP expression, they used a technique called flow cytometry to measure fluorescence from ~10,000 cells per attached RNA sequence and start codon. In this way, they compared translation efficiencies between natural RNA and chemically modified RNA.

They found common trends in altering translation efficiencies when a certain non-AUG start codon received a certain chemical mark. A remarkable discovery, they reported, was the ability of U-to-Psi (pseudouridine) conversion to dramatically increase initiation potentials of CUG, GUG and UUG start codons (and more satisfyingly no affect on AUG). Chemical modification of non-AUG start codons can greatly alter initiation frequencies from these codons, Asano said. Computer simulation played a key role in understanding the mechanism leading to these effects. mRNA translation from non-AUG start codons is an old but new concept. These start codons were used in prokaryotes [bacteria] but our research takes the concept a big step further by highlighting the possibilities of doing so in eukaryotes, including humans.

Asano hopes the medical industry will take note of this new body of data and continue to conduct further research into how to use chemical modified RNA for generating synthetic expression switchesin such a way to stimulate translation activity in a highly targeted way in humans and animals. I am hoping that the companies making mRNA vaccines will use our findings, he said. For example, they could use UUG start codon and chemically modify mRNA by 1m Psi, as Pfizer did with their COVID-19 vaccine. They will allow strong expression of the antigen from the start codon and yet avoid protein expression from cDNA made and integrated into genome by chance.

Asano explained further that so far, no significant risks related to long-term use of various mRNA vaccines have been identified. But there is a small chance that vaccines against retroviruses make vaccine cDNA when the patient encounters these viruses during immunization. If this integrates into the patients genome, the antigen may be expressed in a way that attenuates vaccine production for boosting, he said. But beyond that, the concept is so easy and adds no extra cost. So we hope these techniques are adopted.

- This press release was originally published on the Hiroshima University website

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Jayhawks shine at 2022 Capitol Graduate Research Summit | The University of Kansas – KU Today

Posted: April 19, 2022 at 2:38 am

LAWRENCE Three University of Kansas students received honors during the 19th annual Capitol Graduate Research Summit in Topeka at the end of March. Rohit Singh, Jacob Hodge and Lauren Johnson were each recognized for their outstanding research and presentations at an event that brings together the top graduate student researchers in the state of Kansas.

Rohit Singh, doctoral student in mechanical engineering, received a research award from the Office of Graduate Studies at the Lawrence campus for the project A Novel Technology to Treat Blood-Vessel Related Disease through Space and Time Synchronized Ultrasound and Laser.

A non-visible micron-sized bubble created by ultrasound plus laser inside a blood vessel can treat diseases related to blood vessels, Singh said. It can dissolve blood clots inside vessels in case of deep vein thrombosis disease, and it can close leaky microvessels in the eye to prevent blindness caused by diabetic retinopathy and age-related macular degeneration.

This treatment method aims to improve the human condition and provide a useful alternative to existing treatment techniques that cost anywhere from $15,000 to $20,000 for deep vein thrombosis.

Rohits work explores innovative, non-invasive methods for treating vascular disease, said Jennifer Roberts, vice provost for graduate studies and academic affairs. The procedures he studies would provide preventative treatment for patients with potential blindness due to macular degeneration and diabetic retinopathy.

Jacob Hodge, doctoral student in bioengineering in the M.D.-Ph.D. Medical Scientist Training Program, received a research award from the Office of Graduate Studies at the Lawrence campus for the project Tailoring Stem Cell Therapies to Enhance Regenerative Wound Healing.

My research focuses on using a novel 3D printed biosystem to improve the regenerative capabilities of adult stem cells, Hodge said. Within our bodies, stem cells produce a vast number of compounds that aid in tissue regenerative processes. By utilizing our 3D printed tissue mimetic system, we can control the activity of stem cells and isolate these regenerative compounds to develop personalized medical therapies for a variety of soft tissue ailments, such as wound care.

Hodges research could lead to the development of novel tailorable therapeutics that lessen the economic burden of chronic wounds of patients in the Kansas health care system.

Jacob presented impactful research investigating new techniques for promoting healing for individuals with chronic wounds, Roberts said. Both he and Rohits research showcase the high-quality research underway at KU, and their results show real promise for directly impacting and improving the lives of Kansans.

Lauren Johnson, medical student in the School of Medicine, received a research award from BioKansas and the Office of Graduate Studies at the KU Medical Center for the project Should Breast Cancer Patients Have Preoperative Biopsy of Borderline Abnormal Axillary Lymph Nodes?

Johnsons research has implications for the future treatment of breast cancer patients in Kansas by making treatment more affordable.

The goal of my research project was to determine if a preoperative biopsy of borderline lymph nodes is helpful in the management of breast cancer patients, Johnson said. We found that biopsy is more often an unnecessary procedure as it was only helpful in 32% of patients. We hope this finding can limit travel time, financial burden and unnecessary procedures for breast cancer patients in Kansas.

The free Capitol Graduate Research Summit provides an opportunity for the public as well as Deputy Secretary of Business Development Paul Hughes and state senators and representatives to learn more about the important work of graduate students across the state.

Founded by graduate students 19 years ago, the summit brings attention to the innovative research conducted by students at state universities and emphasizes the public benefits of graduate students research. KU students joined graduate students from Emporia State University, Fort Hays State University, Kansas State University, Pittsburg State University and Wichita State University at the summit.

Top photo:From left to right, Kyung M. Min, Julia Russell, Max S. Fairlamb, Lauren Johnson, Amy Herman, Samantha Cintron, Elizabeth Thoenen, Siddharth Subham, Rohit Singh, Jacob Hodge and Micah Unruh pose after the Capitol Graduate Research Summit. Credit: Genevieve Prescher.Right photo: Jacob Hodge presents his project to Jennifer Roberts, vice provost for Academic Affairs and Graduate Studies.Credit: Genevieve Prescher.

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Four researchers named recipients of the University Scholarly Achievement Award | The University of Kansas – KU Today

Posted: March 25, 2022 at 1:45 am

LAWRENCE Four midcareer faculty members at the University of Kansas will receive an award in recognition of their significant research or scholarly achievements in their field.

The University Scholarly Achievement Award recognizes truly outstanding scholarly or research contributions, with one award given each year in each of four categories: arts and humanities; medicine and clinical sciences; science, technology and mathematics; and social science and professional programs.

This years winners:

These four scholars have all helped to elevate our university through their work, and I look forward to helping them celebrate their successes, said Chancellor Douglas A. Girod. Taken together, these faculty members and their inspiring achievements demonstrate the breadth and depth of the contributions to society that are possible through the work of one of Americas leading research universities.

A panel chaired by Dave Tell, professor of communications studies, reviewed the nominations from colleagues at KU and across the nation.

These four winners along with the winners of other annual research awards will be honored at the University Research Awards ceremonyfrom 7-9 p.m. April 5 at the Lied Center of Kansas. The event will be hosted by the chancellor, and all faculty and staff are invited to attend to help celebrate the universitys top researchers from both the Lawrence and KU Medical Center campuses.

Additional information about each of this years recipients and their work from the nomination materials is below.

Misty Schieberle

Misty Schieberlemade a once-in-a-lifetime discovery that has changed the landscape of late medieval literary studies. Schieberle effectively found a literary Holy Grail: a stunning discovery of a 15th-century manuscript by a prominent English author, royal secretary to Henry IV, Thomas Hoccleve. Schieberles discovery and article, A New Hoccleve Literary Manuscript, substantially reorients approaches to Hoccleve, his original English poetry, and to 15th-century language and literature.Thisdiscovery placesSchieberleamong the few elite researchers who have discovered a new manuscript written by a medieval author. The article in which she announced her discovery pushed a record number of downloads before it was printed. Her discovery has rocked the world of medieval studies in English, history and French as well as in book history/manuscript studies.

Soumen Paul

The body of Soumen Pauls work has clinical implications for pregnancy-associated disorders, pregnancy loss and perinatal pathology. Paul is a leading researcher in the field of stem cells, vascular biology and hematopoiesis, which he has applied to the areas of pregnancy and early intrauterine development, with emphasis on the pioneering fields of embryonic stem cells and trophoblast stem cells. Pauls laboratory first discovered the importance of a transcription factor, GATA3, in early stages of trophoblast development and embryo implantation. Subsequently, he also identified the importance of another GATA factor, GATA2, in this process.His discoveries have been used as a benchmark of early trophoblast development by scientists all over the world in the field of regenerative medicine.Thus, Pauls research has contributed novel and fundamental discoveries that are highly cited by scientific peers worldwide. In addition to his strong funding track record and significant scientific contributions, Paul has invested immense time in the training and mentoring of KUMC graduate students, postdoctoral fellows and faculty.

Amy Burgin

Amy Burgin is an outstanding scholar who works at the interface of biogeochemistry, aquatic ecology, microbial ecology, ecosystem ecology and hydrology to address environmental problems. Her work looks at some of the fundamental issues facing the planet today:What is the role of climate change in degrading waterquality? How do agricultural practices impact streams? How donon-perennial streams influence water chemistry? In addition to questions of global concern, she addresses important local issues such as the impact of a decommissioned fertilizer plant on Kansas River water quality. Burgin has secured more than $8 million in federalgrants, published 50 peer-reviewed papers and is a leader in her fieldfor performing cutting-edge research across a range of aquatic systems. In 2021, she and her studentspublished "A practical guide for undergraduate research" that many, evenoutside her field, use to build inclusive research spaces. She alsopublished a paper providing concrete suggestions for supporting academicmothers during COVID-19 and beyond.

Brian Boyd

Brian Boyd is the director of Juniper Gardens Childrens Project in Kansas City, Kansas, a part of the KU Life Span Institute. His research focuses on the development andevaluation of evidence-based practicesto improve outcomes for children with autism.His inquiry is at the forefront of community-engaged research and scholarship and building community partnerships to implement evidence-based practices in school and community contexts. His work also focuses on issues of implicit bias and race and how these issues affect the lives and outcomes of children of color, including children with disabilities.His work hasshaped the directionof autism and disability research, reflected in over 80 peer-reviewed publications, over $20 million in current grant funding from multiple sources, and strong and sustained community impacts.

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COVID-19 directly damages, creates scar tissue on the kidneys, study finds – WDAF FOX4 Kansas City

Posted: January 5, 2022 at 2:19 am

(StudyFinds.org) Although studies show COVID-19 is capable of infecting a patients kidneys, the viruss exact impact on the organs has been unclear until now. A team of German and Dutch scientists report COVID-19 causes direct cellular damage within the kidneys, contributing to tissue scarring.

Conducted at the RWTH Uniklinik Aachen in Germany and the Radboud University Medical Center in the Netherlands, study authors assessed and compared kidney tissues among COVID-19 ICU patients, other patients in the hospital for a non-COVID-related lung issue, and a group of healthy people. Results show kidney tissue from the COVID-19 patients showed much more tissue scarring than others.

The first phase of the investigation clearly established that COVID-19 damagesthe kidneys. Next, researchers set out to determine how the virus accomplishes this.

Many recent studies indicate that some of COVID-19s more severe symptoms emerge due to an overreaction of the bodys immune response and too much inflammation, not coronavirus itself. Is this the case for the kidneys as well, or is COVID-19 inflicting damage on these organs directly?

The team created a series ofmini kidneys, called organoids, by culturing them in a lab setting. Developed using stem cells, the organoids featured many different kidney cells, except immune cells. Researchers infect each organoid with COVID, allowing the team to observe the virus direct impact on kidney cells. Once again, scientists noted kidney organoid scarring as well as accompanied signals that contribute to the scarring process.

These findings strongly indicate that the coronavirus itself, notinflammationor any other systemic effects, is responsible for the observed kidney damage seen in COVID-19 patients.

In our study, we thoroughly investigated the causal damaging effects of the Coronavirus in the kidneys. The infected kidney organoids show that the virusdirectly causes cell damage, independent of the immune system. With this work, we found a piece of the puzzle showing the deleterious effects the virus can have in the body, says co-researcher Jitske Jansen in amedia release.

These conclusions are quite similar to the findings of another, larger American study encompassing over 90,000 COVID-19 survivors. Just like this work, that research found that reported declines in kidney functioning amongCOVID-19 patientsis likely due to the coronavirus itself.

Kidney fibrosis, or scarring, is a serious long-term consequence that can occur virtually after any injury to the kidney and correlates with kidney function. Our work shows kidney scarring in COVID-19 patients, which provides an explanation why the virus might cause kidney functional decline as demonstrated in other studies. Long-term follow-up studies will provide further insights into kidney-related pathologies caused by SARS-CoV-2, concludes co-researcher Katharina Reimer.

Thestudyis published in the journalCell Stem Cell.

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The controversy being created about the origins of the virus that causes COVID-19 – Frontline

Posted: July 6, 2021 at 2:07 am

The famous question about whether the world as we know it arose from evolution or creation was settled long ago in favour of evolution and against religious bigotry. But the old debate resurfaced, only in a different garb, during the pandemic. The question is posed thus: did the SARS-CoV-2 virus, which causes COVID-19, naturally evolve from bats through an intermediary to humans or was it engineered in a laboratory in Wuhan, the capital of Hubei Province, and leaked accidentally or intentionally?

COVID-19, perhaps one of the most virulent pandemics in the past 100 years, has exposed the frailties of public health systems in many countries, as evidenced by the massive loss of lives and livelihoods across the world. But it has also shown the power of science and technology, especially the open and quick sharing of data and results. Obversely, the ensuing infodemic has brought with it a tide of misinformation, chiefly the manufactured controversies on whether the SARS-CoV-2 virus evolved naturally or was deliberately or artificially created by Chinese scientists who then caused its spread intentionally or otherwise.

Here, we argue that the virus, which appears so perfect and complexly suited to infecting humans and for transmission amongst them, is most likely of natural evolutionary origin. Various statements and articles speculating that the virus was created by design and released through laboratory leaks appear to lack scientific credibility and border on conspiracy theories. The push by some scientists and governments for investigations, in the name of biosafety monitoring, into a possible laboratory leak from the Wuhan Institute of Virology (WIV) appear to be driven by paranoia or a Chinaphobia.

Nearly two centuries ago, Charles Darwin said in his Origin of Species: To suppose that the eye with all its inimitable contrivances .could have been formed by natural selection, seems, I freely confess, absurd in the highest degree. When it was first said that the sun stood still and the world turned round, the common sense of mankind declared the doctrine false .Reason tells me, that if numerous gradations from a simple and imperfect eye to one complex and perfect can be shown to exist, ...then the difficulty of believing that a perfect and complex eye could be formed by natural selection, though insuperable by our imagination, should not be considered as subversive of the theory.

Also read: On the political economy of pandemics

Viruses are opportunistic and take advantage of unusual situations and the weaknesses of their hosts. In most cases, humans invite viral pathogens upon themselves by invading and occupying biological spaces to the detriment of other animals, thereby also presenting viruses with greater opportunities to infect them. The precise path that leads a particular virus jumping from its reservoir population to humans is mostly fortuitous, difficult to determine and, in some instances, has remained inconclusive.

The influenza pandemic that started in 1918, which was popularly called the Spanish flu though the origin was not in Spain but in Haskell County, Kansas, United States, infected about 500 million people and resulted in the death of possibly 50 million. It is now known to have been caused by the virus H1N1 with genes of avian origin, although the exact origin has still not been conclusively established. It is thought to be of zoonotic origin from birds because since then there have been several similar influenza virus pandemics: in 1958 (H2N2), 1968 (H3N2) and 2009 (H1N1 pdm09). Interestingly, H1N1 pdm09 was also called swine flu because it contained a sequence segment similar to the Eurasian swine influenza virus from 1992. It is estimated that 0.001 per cent to 0.007 per cent of the worlds population died of respiratory complications associated with the H1N1 pdm09 virus infection in the first 12 months of the virus circulation. Where did that virus jump from? No intermediate host has been identified. Thankfully, there was no laboratory leak conspiracy theory for that episode.

A highly pathogenic avian influenza (HPAI), A(H5N1) was first detected in humans in 1997 during an outbreak among poultry in Hong Kong. H5N1 has continued to circulate and been detected at various times, for instance in 2003 and 2014. It has been found that low pathogenicity avian influenza viruses (LPAIVs) are generally asymptomatic in their natural avian hosts. LPAIVs can evolve into highly pathogenic forms, which can affect avian and human populations with devastating consequences. The acquisition of multiple amino acids with positively chargeable side chains such as lysine (K) and arginine (R) in the haemagglutinin cleavage site creates what is called a polybasic motif because of the presence of exchangeable hydrogens in the side chains. Thus, for example, the polybasic motif (RERRRKKR) can be cleaved by proteases such as furin in the human host. This leads to the switch to a HPAI virus from LPAIV precursors facilitating viral entry into cells. Proteolytic cleavage regulates numerous processes in health and disease.

Also read: COVID-19: No endgame in sight

The ubiquitously expressed protease furin cleaves a plethora of proteins at polybasic recognition motifs. Mammalian substrates of furin include cytokines, hormones, growth factors and receptors. A viral pathogen generally needs to bind to a receptor in human cells in order to make its entry. The receptor binding decides the type of cells the virus infects. Receptor binding is often enhanced by proteolytic cleavage of the viral protein that binds. Since the virus can reproduce and make the proteins it needs only after entry into cells, it makes use of the proteases in the host. So, not surprisingly, numerous viral pathogens exploit the ubiquitous nature of furin to enhance their virulence and spread. A furin cleavage site occurs in SARS-CoV-2, and its occurrence is the centrepiece of the conspiracy theories, the so-called smoking gun if you will.

Acquired immune deficiency syndrome (AIDS), which was first reported in 1981 from New York City, has killed about 35 million plus people so far. A retrovirus, now termed human immunodeficiency virus type 1 (HIV-1), was subsequently identified as the causative agent of what has since become one of the most devastating infectious diseases to have emerged in recent history. The zoonotic origin of HIV-1 was unclear for more than a decade and was discovered by pure luck and some hard work.

The HIV-1 is similar in sequence and genomic organisation to viruses found in chimpanzees (simian immunodeficiency virus, or SIVcpz). However, there was a low prevalence of SIVcpz infection in wild-living animals. Moreover, chimpanzees were present in geographic regions of Africa, but AIDS was not initially seen there. This along with the differences between HIV-1 and SIVcpz cast doubts on chimpanzees as a natural host and reservoir for HIV-1. It was then suggested that another, as yet unidentified, primate species could be the natural host for SIVcpz and HIV-1. The link was finally established in 1999. A chimpanzee (named Marilyn) of the subspecies Pan troglodytes troglodytes had been caught in the wild in Africa and then exported as an infant to the U.S. for research. She had not received any blood contaminated with HIV. But, during a sero-survey in 1985 amongst 98 chimpanzees, Marilyn showed a high level of antibodies to HIV-1. She died shortly afterwards giving birth to stillborn twins. A polymerase chain reaction analysis in 1999 of the spleen and lymph node tissues retrieved from frozen samples showed the presence of the virus now called SIVchzptt, which is the closest relation to HIV-1, and confirmed its zoonotic origin.

Also read: India's vaccination policy: A U-turn and a spin

Interestingly, the HIV-1 envelope protein initiates infection by mediating the fusion of the viral envelope with the cell membrane. For this to occur, the envelope protein has to be cleaved by host proteases such as furin at a polybasic motif in a loop connecting two regions. In fact, in an attempt to bolster the conspiracy theory that SARS-CoV-2 was man-made, claims have been made that Dr Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH), holds patents of an HIV component used to create COVID-19.

The severe acute respiratory syndrome (SARS) pandemic of November 2002 to July 2003, which was caused by a coronavirus now called SARS-CoV, affected about 8,000 people in more than 30 countries. In May 2003, sampling of 25 animals in a wet market in Hong Kong showed the presence of a coronavirus in three masked palm civets, one racoon dog and two Chinese ferret badgers with 99.8 per cent of its sequence identical to the human SARS-CoV. Subsequently, serological and epidemiological surveys pointed to traders of palm civets having been infected with SARS-like viruses earlier. Studies in 2004 suggested that a small proportion of healthy individuals in Hong Kong had been exposed to SARS-CoV-related viruses at least two years before the SARS outbreak reached Hong Kong in mid February 2003.

In 2005, two groups of researchers demonstrated that bats were natural reservoirs of SARS-like viruses. There is now evidence to suggest that there are four possible routes of transmission of SARS-CoV: animal-to-human, animal-to-animal, human-to-human and human-to-animal. Studies with animals showing infectivity to SARS-CoV have shown that inter-species contact and cross-species virus transmission (i.e. spillover) are essential and sufficient to cause epidemic emergence. Sustained transmission and virus adaptation within the spillover species determine the magnitude and scope of subsequent disease outbreaks. For example, SARS-CoV uses the angiotensin-converting enzyme (ACE2) as a receptor for its spike protein to bind to and gain entry into human cells. The spike protein also gets cleaved by a host protease (not furin), which enables the binding and fusion of the viral envelope with the cell membrane. It was found that the spike protein in the virus isolated from human patients in the 2002-03 outbreak bound more efficiently to the ACE2 receptor than the virus isolated from palm civets or from humans with mild cases in 2004. It took about three years after the outbreak of SARS-CoV to establish all this.

Also read: COVID-19: Perils of vacuous claims

However, a study in 2012 isolated a SARS-like coronavirus that was able to utilise ACE2 in humans, civets and in Chinese horseshoe bats for cell entry. This virus (bat SL-CoV-WIV1) offers strong evidence that SARS-CoV originated from a bat reservoir and suggests that an intermediate host may not have been required to facilitate adaptation to human ACE2. Curiously, in 2009 an article in the journal Proceedings of National Academy of Sciences of the United States of America revealed that a group at Cornell University engineered SARS-CoV to introduce a furin cleavage polybasic site to study the proteolytic activation of SARS-CoV.

In November 2012 came the first case of the disease that since May 2013 has been called the Middle East respiratory syndromes (MERS), which is caused by the MERS coronavirus (MERS-CoV). The outbreak started in the Middle East and has now spread to about 24 countries, affecting people and causing deaths, albeit in comparatively smaller numbers than COVID-19. In June 2014, it was found that the sequence of the virus from a man who became sick with MERS and that isolated from the camel he was tending were nearly identical. It was concluded that the camel was the intermediate host from which the virus could have jumped to humans. But a 2015 study showed that transmission from camels to humans is rare. This raises questions about whether the camel was really the intermediate animal for transmission. MERS-CoV does not use ACE2 as the receptor but binds to dipeptidyl peptidase 4 (DPP4). However, it has a furin cleavage site similar to that in SARS-CoV-2, which helps in its infection.

In China, on December 29, 2019, local hospitals in Wuhan using the surveillance mechanism for a pneumonia of an unknown aetiology that was established in the wake of the 2003 SARS outbreak identified the first four cases of COVID-19, which were all associated with the seafood wholesale market in Wuhan. On December 31, the Chinese Centre for Disease Control and Prevention dispatched a rapid response team to Wuhan to accompany the Hubei provincial and Wuhan city health authorities who were conducting an epidemiological and aetiological investigation. Scientists of the WIV made the sequence of the virus available to the international community through a manuscript that was submitted to the journal Nature on January 20, 2020. The paper was published online on February 3. It showed that the sequence of the virus from human patients was 94.4 per cent identical to SARS-CoV and 96.2 per cent identical to the virus from bat samples (RaTG13) collected previously from caves in Yunan.

Also read: COVID and other diseases: An Animal Farm perspective

On February 11, the International Committee on Taxonomy of Viruses named the virus SARS-CoV-2 because of its close relationship to SARS-CoV. The World Health Organisation (WHO) called the disease COVID-19 to distinguish it from the earlier SARS. The disease rapidly spread to many countries, and the WHO declared it a pandemic on March 11. The virus was shown to use the ACE2 receptor for binding and cell entry and was aided by cleavage by protease transmembrane serine protease 2 (TMPRSS2). A furin protease cleavage site not seen in SARS-CoV was found in this virus, and the cleavage at this site enables the entry of the virus into the cell.

To date, the disease has caused 177.5 million cases and 3.8 million deaths worldwide, and 1.99 million sequences from infected cases have been made publicly available. These sequences have shown the evolutionary changes that are happening in the virus. No other virus or disease in history has been subject to such close scrutiny and public discussion, thanks to the sharing of data and findings facilitated by modern communication, including social media channels. The first reports of the virus and disease were from China, which is becoming a major player in the world economy and is threatening to surpass existing powerhouses. The fact that the WIV specialises in coronaviruses, and has allegedly been engaged in collaborative work with U.S. institutions on gain of function research because of the prevalence of these viruses in the region, gave rise to conspiracy theories spread by right-wing governments and scientists.

At the beginning of 2020, several scientists/virologists were of the opinion that the question of whether the virus was the result of natural evolution should be answered in the affirmative. But because of the elections in the U.S., President Donald Trump needed an enemy to blame and attack in order to distract attention from his poor handling of the pandemic despite prior warnings from the U.S. Centres for Disease Control and Prevention. When the horrifying images of people being buried in New York were splashed in the media, he chose to call the virus a China virus. He even declared that he had found the cure in the form of hydroxychloroquine. But in the beginning, a few reputed scientists even declared the disease an ordinary influenza. Later, the vicious nature of the pandemic became clear, and the whole world had to look for solutions that would work in the temporary short term as well as the permanent long term.

Once the U.S. elections were over, the new President brought in measures to help the vulnerable sections and to ramp up vaccinations. Now the question about the origin of the virus, which scientists were working on anyhow, became politicised to align with the new policy to challenge the emerging force of China. The discredited conspiracy theory that the virus was a bioweapon engineered at a laboratory in Wuhan is now brought out as new wine in old bottles with the claim it leaked from that same laboratory.

Also read: COVID-19: Vaccine follies

So what evidence has been marshalled in support of the contending conjectures and what should be done now? Coronaviruses are not new. They have been around for at least a few decades. Jemma Geoghegan, the well-known virologist from New Zealand who was prominent in her countrys prompt COVID-19 response, said: SARS-CoV-2, the virus that causes the COVID-19, is closely related to other viruses that exist in nature. This virus is likely to have taken a path similar to SARS in 2003, viz., from animals to humans. Jemma Geoghegan explores the role that size, structure and mode of transmission of viruses play in the prediction of whether a virus will infect humans and cause a pandemic. She explained that prediction was difficult because of the vast number of viruses and said it was simply impossible to predict... whether a newly discovered animal virus could jump into humans and cause a pandemic. She also mentioned that five coronaviruses have emerged in the past and the intermediary animal responsible for COVID-19 remains unclear. Farm animals such as rabbits could be a possible intermediary for many viruses, but more studies are required to establish this conclusively. Ninety-six per cent of the genome sequence of SARS-CoV-2 is common to that found in bat coronaviruses. That the spike protein of SARS-CoV-2 can bind effectively to human cells is most likely a result of natural selection rather than manipulation in a laboratory. The backbone of the virus seems to be linked to bats and pangolins and is quite different from anything available in laboratories.

The genome of SARS-CoV-2 shows thousands of differences from its closest relative, according to Jonathan Stoye, group leader of the Retrovirus-Host Interactions Laboratory at the Francis Crick Institute in the United Kingdom. Now the changes that have been observed in the nucleotide sequence of the SARS-CoV-2 genomes sequenced so far clearly indicate that it is highly improbable for modifications that span such a large evolutionary distance to have taken place in a laboratory. This therefore suggests that the variations happened in animals, either bats, which form the reservoir for coronaviruses, or an intermediary animal in the wild, which is yet to be discovered.

The most important supposed villain in this is said to be the spike glycoprotein, which helps the virus bind to the specific ACE2 receptor. A cleavage of the spike protein by the host proteases, one of which is furin, helps facilitate the entry. This was the smoking gun the science correspondent Nicholas Wade attributed to the Noble laureate David Baltimore. While Wade used this information and spun stories beyond what is known, Baltimore himself withdrew from Wades surmises. In an article in Current Science (June 10, 2021), Prof. P. Balaram developed Wades arguments and gave further impetus to the improbable thesis that the virus was manipulated/engineered in the WIV and leaked. This scenario was also the favourite among the conspiracy theorists initially. However, U.S. scientists immediately responded that nature was responsible for the virus reaching humans through an intermediary via slow evolutionary processes. Moreover, many viruses use the furin cleavage site, and it is not unique to SARS-CoV-2. An analysis of all coronavirus sequences published in the journal Stem Cell Research in December 2020 showed that furin cleavage sites in spike proteins naturally occurred independently multiple times in coronaviruses.

Also read: Misplaced optimism as COVID numbers go down

A recent report in the journal Cell showed the great diversity of viruses in least horseshoe bats, or Rhinolophus pusillus (https://doi.org/10.1016/j.cell.2021.06.008 ). It showed that apart from the previously reported coronavirus sample, RaTG13, two others, RpYN06 and RmYN02, had similarities over the whole genome. A bioRxiv reprint in March 2021 used the available 1,58,118 public seasonal genome sequences of hCoV, SARS-CoV-1, SARS-CoV-2 and MERS-CoV and noted that the current sampled diversity of seasonal coronaviruses had emerged over a 70-year-period, punctuated by the emergence of new lineages at intervals ranging from 5 to 20 years.

Interestingly, in July 2020, a group published an analysis of the more than 45,000 SARS-CoV-2 sequences from infected people then available, which showed the mutations and deletions that happened in the furin cleavage site, and concluded that the furin cleavage site might not be essential for SARS-CoV-2 to enter human cells in vivo. This shows that the virus in its passage through human cells is capable of losing the furin cleavage site. So it is not a site that is essential to virus infection, and this makes the case for the artificial insertion of this sequence to create a new virus much less appealing. A study published in PLOS Biology in March 2021 showed that the bat virus closest to SARS-CoV-2, RmYN02 (sharing an ancestor from about 1976), arose from a recombination within coronaviruses in bats and shares genetic features similar to SARS-CoV-2. This suggests the possibility that SARS-CoV-2 could have evolved in bats and directly jumped to humans without the need for an intermediate animal.

Although it is possible to conclude that there may be an undiscovered facilitating intermediate species, the results support the premise that the progenitor of SARS-CoV-2 was capable of efficient human-to-human transmission as a consequence of its adaptive evolutionary history in bats, not humans, that created a relatively generalist virus capable of infecting many hosts. Thus, finding the closest relative to SARS-CoV-2 could then be a matter of screening diverse bat populations. This really warns us against jumping the gun, whether it is smoking or not, and concluding that SARS-CoV-2 does not have a natural origin. A letter published in Science on May 14 said: We must take hypotheses about both natural and laboratory spillovers seriously until we have sufficient data. A proper investigation should be transparent, objective, data-driven, inclusive of broad expertise, subject to independent oversight, and responsibly managed to minimise the impact of conflicts of interest.

Also read: India needs to spread its bets on vaccines: Dr Satyajit Rath

But a couple of months earlier, The Lancet published a letter emphatically dismissing conspiracy theories and saying that sharing of data is being threatened by disinformation and rumours. This issue of sharing data and information has become more about political sloganeering, in which some scientists too have joined in, than about science. Scientists from various countries have analysed the genomes of SARS-CoV-2 and come to the conclusion that this virus originated in the wild as did many other pathogens. The presidents of the U.S. national academies of sciences, engineering and medicine have backed this and warned that conspiracy theories create only fear, rumours and prejudice and jeopardise the global fight against the virus. They said they supported the call from the WHO Director General to promote scientific evidence and unity over misinformation and conjecture.

The problem with conspiracy theories is that they usually provide one point of speculative evidence that forms the basis for further speculative theorising. Essentially, they all turn to one final definitive source to rest their case. In this case, Nicholas Wades publication of his speculative thesis in Bulletin of the Atomic Scientists has been used to spread the canard that the pandemic was caused by negligence or deliberate action in Wuhan.

Incidentally, Wades book A Troublesome Inheritance: Genes, Race and Human History (2014) drew sharp criticism from 130 scientists for its racist overtones. They said in a letter to The New York Times: Wade juxtaposes an incomplete and inaccurate account of our research on human genetic differences with speculation that recent natural selection has led to worldwide differences in I.Q. test results, political institutions and economic development. We reject Wades implication that our findings substantiate his guesswork. They do not. We are in full agreement that there is no support from the field of population genetics for Wades conjectures. In the past, many people have criticised him for misreporting their remarks in his articles.

No doubt more data is needed on the nature of studies at the WIV. The institute is one of international standing where research work is carried out in collaboration with scientists from the U.S., Europe, Australia, Japan and India (the National Centre for Biological Sciences, or NCBS) with funding from these countries. It is one of the two laboratories in China to have a biosafety level of 4 (the highest level). Even the U.S. Department of Defence has funded programmes at the institute. It is only natural that researchers from these countries would demand a high degree of transparency about safety procedures at the WIV, including the recording of accidents and the corrections undertaken. The WIV has a high level safety procedures that is not matched even by the Indian Department of Atomic Energyfunded NCBS. There has even been a collaboration on the bat viruses from Nagaland involving scientists from the NCBS. A needless controversy has now been created about whether proper approvals were obtained from the Indian Council of Medical Research, the Ministry of External Affairs, and so on, for such studies. This is because the issue has deliberately been politicised with the intention of derailing international scientific collaborations with entities based in China.

Also read: The B.1.617 variant of COVID-19 that emerged in India is spreading to South Asia and beyond

To this end, conspiracy theorists have attempted to link Dr Fauci, the face of the COVID-19 response in the U.S., to the laboratory leak theory. His office provided a research grant of $6,00,000 for five years (which the NIH eventually halted) to an American organisation, EcoHealth Alliance, working with the WIV. Dr Fauci received an email on April 18, 2020, from the zoologist Peter Daszak thanking him on behalf of the staff of EcoHealth Alliance for rejecting the laboratory leak theory. Actually, Dr Fauci did not reject it but only claimed it was less likely compared with the zoonotic origins theory. Republican senators in the U.S. introduced a Bill to remove Dr Fauci, who has advised several Presidents across parties, from his post.

Harping on conspiracies vitiates the atmosphere to the point where research involving international collaboration, particularly on virus mutations and the required responses, becomes increasingly difficult. In an article in Forbes magazine, Ethan Siegel lists out the strident remarks that have been made about the virus, which cannot, in the language of the scientific method, even be termed hypotheses: 1. It was a bioweapon developed in Wuhan. 2. Dr Fauci was directly involved in funding the programme in the laboratory that created the virus 3. Dr Shi Zhengli, the bat woman, was the brains behind the research to unleash the virus 4. Some kind of banned/unregulated research in gain of function was being done to modify a coronavirus, which resulted in the virus that causes COVID-19. All these are extraordinarily improbable compared with the hypothesis that the disease has zoonotic origins.

But the international collaboration the pandemic has brought about among scientists, virologists, medical professionals and public health administrators is extraordinary. They will eventually agree that Darwin still rules the world of cell biology.

S. Krishnaswamy is a retired professor of biotechnology earlier from Madurai Kamaraj University, Tamil Nadu. T.R. Govindarajan is a retired professor of physics from the Institute of Mathematical Sciences, Chennai.

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Kelly lauds $21 billion state budget bill, vetoes $500,000 …

Posted: June 6, 2021 at 1:45 am

TOPEKA Gov. Laura Kellys enthusiasm when signing a new $21 billion state government budget couldnt be dampened with the lone veto of an earmark for research using stem cells to search for a treatment of severe COVID-19 cases.

Im proud of this bipartisan, fiscally responsible budget that demonstrates what lawmakers can get done when we work together, Kelly said. This budget includes increased funding for disability services, the criminal justice system, mental health services and higher education.

She said the appropriations would deliver critical services so that Kansans, businesses and local governments continue with the COVID-19 recovery.

The House voted 98-21 to approve Senate Bill 159, while the Senate voted 26-12 on the bills behalf. Its possible the Legislature would attempt to override the governor Wednesday when convened for the final day of the annual session, but there remained sharp division between legislators who believe the state was spending too little or too much.

I refuse to give more of my hard-earned money to government that has an endless appetite for spending with no true results for the great people of Kansas, said Rep. David French, a Lansing Republican among House members opposed to the bill.

The budget for the fiscal year starting July 1 and signed into law Friday raised state spending by $17 million to provide salary increases for employees in the Kansas court system and to add 70 new court services officers.

The Legislature rejected proposals to provide across-the-board pay raises for state workers, with some lawmakers declaring it unfair to give increases to state employees who didnt lose jobs during the pandemic. Kelly recommended state employees get a 2.5% salary bump.

Is the irony lost on anyone else that the very judges salaries that we are increasing as a good job are the same judges that have stepped all over our toes with massive education funding? said Rep. Tatum Lee-Hahn, a Ness City Republican irritated by previous court rulings that state aid to K-12 schools was unconstitutionally low. This is a huge reason we cannot get control of our states budget.

Topeka Rep. Vic Miller, one of the few Democrats to vote against the budget, did so for a reason contrary to Lee-Hahns position. Miller said he voted no because the rest of state employees were also deserving of a pay raise.

The law did authorize issuance of bonds to finance the $120 million renovation of Docking State Office Building next to the Capitol and $65 million in bonds for construction of a Kansas Department of Health and Environment lab in the Topeka area.

The measure funneled $53 million to public and private universities and colleges for scholarships, staff recruitment and economic development. The extra funding was designed to comply with federal requirements on higher education institutions receiving federal COVID-19 aid.

The bill directed $3.6 million at the Board of Indigents Defense Services to boost the rate paid attorneys. It included $3 million to support implementation in Kansas of the nationwide 988 hotline for people to connect with mental health or suicide prevention counselors.

Kelly vetoed a provision setting aside $500,000 for the University of Kansas Medical Center to conduct clinical trials for a COVID-19 treatment using stem cells derived from umbilical cords. Critics said the modest level of funding to the Midwest Stem Cell Therapy Center would make the project not realistic or even feasible, because a typical clinical trial could cost 20 times the amount appropriated.

Given those realities and the proven effectiveness of COVID-19 vaccines and treatments that are now widely available, we should focus our efforts on increasing the number of Kansans who are vaccinated so that we can prevent infections, severe illnesses and deaths, Kelly said.

Sen. Mike Thompson, R-Shawnee, said he was disappointed the governor undermined research on COVID-19. He said $500,000 was enough to support a clinical trial involving 10 people.

There is currently no treatment available for COVID-19 patients who have developed the most severe symptoms, including pneumonia, said Thompson, among Republicans critical of Kellys handling of the pandemic. There is an urgent need for a medical intervention beyond supportive therapy for these patients.

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Kelly lauds $21 billion state budget bill, vetoes $500,000 ...

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