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UToledo Research Earns Spot on International Space Station

Protein crystals prepared by researchers at The University of Toledo and grown aboard the International Space Station could one day help scientists better understand basic life functions at the molecular level, unlocking some of the greatest secrets of biochemistry.

Earlier this year, a SpaceX capsule loaded with more than 150 crystals splashed down in the Pacific Ocean after spending six months and traveling some 50 million miles in low Earth orbit. Following retrieval by NASA, the experimental cargo was transported to the Oak Ridge National Laboratory for analysis.

Victoria Drago, a third-year Ph.D. candidate in biochemistry, helped design the unique crystal growth system that flew aboard the International Space Station.

UToledo’s mission? Growing near-perfect crystals large enough to be used in neutron diffraction — a high-tech process that enables researchers to map out the precise location of a molecule’s every single atom.

“We have been able to view our metabolic world at the atomic level for quite some time now. However, hydrogen, the smallest of atoms and responsible for most of the activity, cannot be seen,” said Dr. Timothy Mueser, professor of chemistry and biochemistry in the UToledo College of Natural Sciences and Mathematics. “Neutrons allow us to see the missing hydrogens, but the signal is very weak. We need extraordinarily large crystals for the technique to work, and crystal growth in microgravity on the International Space Station is vital to achieving that.”

Mueser’s lab is one of only a handful of groups in the United States working on neutron crystallography. They’ve sent experiments on three prior space flights and regularly collaborate with Oak Ridge National Lab and Institut Laue-Langevin, a leading nuclear research facility in Grenoble, France.

“There’s a lot of good research that’s going on here,” said Victoria Drago, a third-year Ph.D. candidate in Mueser’s lab, who helped design the unique crystal growth system aboard the International Space Station. “From the 2018 flight, we determined that our setup works. The only thing we saw problems with was that we were not getting much growth when they returned. That indicated we didn’t leave the crystals up there long enough. On the most recent flight, we got back several neutron-worth crystals.”

On that flight, which launched in July 2016, the International Space Station National Lab allowed the experiments to stay on board for six months. The extra time improved results dramatically. Several crystals on the flight grew five to 10 times larger than comparable crystals previously grown on Earth and contained no noticeable defects.

Some of those crystals are scheduled to be taken to the Institut Laue-Langevin this spring for further validation and, hopefully, a complete neutron diffraction analysis. That analysis could unlock precise atomic details about the active form of vitamin B-6, which is essential for a number of metabolic processes in the human body.

Equally — if not more — important is proving the viability and success of UToledo’s novel technique for growing crystals in microgravity.

After disappointing results with another commercially available growth system on their first flight, UToledo researchers developed their own system, which was approved by NASA for the second and third flights. Slightly larger than a deck of playing cards and costing about $100, the system is significantly less expensive and smaller than others. With real estate aboard the International Space Station extremely limited and costly, the size of UToledo’s apparatus makes it particularly appealing.

The hope is that UToledo’s system may make it possible for an explosion of new research to define an array of metabolic processes with major ramifications in the understanding of human health and treatment of disease.

“We’re not in the field where we’re going to be designing drugs, but it could be really useful in that if you truly understand the mechanism at a molecular level, versus making speculations, you can better inhibit it,” Drago said. “We’ve already shown with some of our previous research that we can redefine mechanisms this way to make things a little bit clearer. Down the road, people could use this for better drug design.”

Drago, who completed an undergraduate degree in biochemistry at UToledo, returned to UToledo to pursue her doctorate specifically to work in Mueser’s lab. The decision has afforded her unique opportunities, including being present for the launch of two SpaceX rockets that carried their experiments to the International Space Station and working closely with national and international laboratories.

“I’ve got to experience a lot because of coming here. I wouldn’t be doing what I’m doing and I wouldn’t have the connections I have if I was anywhere else,” Drago said.

Growing protein crystals in space offers several benefits over earthbound growth, but one of the most prominent is that it slows down the entire process.

“Slow crystal growth is good crystal growth,” said Dr. Constance Schall, UToledo professor of chemical engineering, who is one of the researchers involved in the project. “It’s kind of like a crowd trying to get into a door. If you take your time and line everybody up in an orderly fashion, things go much more smoothly. Zero gravity slows the growth and removes convection currents. You end up with much larger and higher quality crystals.”

Smaller, microscopic crystals can be used to map out atomic positioning of proteins via X-ray crystallography, but the process does not show the location of hydrogen atoms or protons.

Neutron crystallography shows those atoms, but it requires the significantly bigger, more perfect crystals that Mueser’s team is growing. Several of the crystals that returned in January were about 1 cubic millimeter.

“This is very exciting work, and I’m grateful to be part of it,” Drago said.” Our Toledo Crystallization Box has the ability to mainstream large crystal growth for the neutron crystallography community, the largest and most time-consuming obstacle in this work. We are in the process of trying to secure more flights with the Toledo Crystallization Box to the International Space Station in order to benefit both our research and others in the field.”

UToledo Teams With National Renewable Energy Laboratory, Partners to Accelerate Promising New Solar Technology

Advancing our country’s global leadership in solar energy technologies, The University of Toledo is a founding member of a new organization called the U.S. Manufacturing of Advanced Perovskites Consortium, which is focused on moving a breakthrough new technology out of the lab and into the marketplace to enhance economic and national security.

The group is working together to accelerate U.S. commercialization of perovskite solar cell technology in partnership with leading domestic companies, including First Solar, one of the world’s largest manufacturers of solar cells and a company that originated in UToledo laboratories.

Members of the Industrial Advisory Board posed for a photo during a meeting in March. They are, front row from left, Daniel Kroupa, BlueDot Photonics; Nancy Terjo, Swift Solar; David Ginger, the University of Washington; Joel Jean, Swift Solar; Joe Berry, NREL; and Jinsong Huang, the University of North Carolina; and back row from left, Stephan DeLuca, Energy Materials Corp.; Gang Xiong, First Solar; Colin Bailie, Tandem PV; Billy Stanbery, NREL; Yanfa Yan, The University of Toledo; Michael Heben, The University of Toledo; Jao van de Lagemaat, NREL; Michael Irwin, Hunt Perovskite Technologies; and Devin MacKenzie, the University of Washington.

Known as US-MAP, the consortium’s founding members are UToledo’s Wright Center for Photovoltaics Innovation and Commercialization; the U.S. Department of Energy’s (DOE) National Renewable Energy Laboratory (NREL) in Golden, Colo.; Washington Clean Energy Testbeds at the University of Washington; and the University of North Carolina at Chapel Hill.

“Perovskites have the potential to become a game-changer for solar and many other fields,” Martin Keller, NREL director, said. “By combining our research efforts, this new consortium will bring this technology to market sooner than if we were all operating alone.”

Perovskites are compound materials with a special crystal structure formed through chemistry.

Dr. Yanfa Yan, UToledo professor of physics, has had great success in the lab drawing record levels of power from sunlight by using two perovskites in a so-called tandem architecture on very thin, flexible supporting material.
Yan’s efforts have increased the efficiency of the new solar cell to about 23%. In comparison, silicon solar panels on the market today have around an 18% efficiency rating.

Dr. Michael Heben, UToledo professor of physics and McMaster endowed chair, also is a leading researcher in this field working on studying the reliability of perovskite solar cells.

“We have a talented team of physicists on faculty making significant advancements using perovskites to make solar energy more affordable, working closely with students and our industry partners,” Heben said. “UToledo is already well-known internationally for its work on cadmium telluride solar cells, which are already being manufactured at large scale by First Solar. We are proud to share our resources and expertise to support U.S. companies in the face of international competition and help the country have control over our energy infrastructure.”

“I applaud The University of Toledo and the National Renewable Energy Lab for their new and exciting partnership advancing U.S. leadership in solar energy technology,” Congresswoman Marcy Kaptur said. “The U.S. Manufacturing of Advanced Perovskites Consortium will move our country and region forward in solar energy development at a time when it is needed more than ever. As the chair of the House Appropriations Subcommittee on Energy and Water Development, I will continue to prioritize Department of Energy programs that help fund these important programs through competitively awarded grant opportunities. I thank The University of Toledo, the National Renewable Energy Lab, and other partnering organizations, including First Solar, for their commitment to solar energy.”

In addition to harnessing sunlight to generate electricity, perovskites have shown promise in a range of other applications, including solid-state lighting, advanced radiation detection, dynamic sensing and actuation, photo-catalysis and quantum information science.

Early research investments by DOE’s Solar Energy Technologies Office, its Office of Science, the Department of Defense and by the domestic industry partners have enabled the United States to engage at the forefront of many of these technology areas and has fostered a vibrant community of industrial leaders.

US-MAP founding members will form the executive board that will oversee successful completion of projects. The executive board and the member institutions will be informed and guided by an industrial advisory board composed of new U.S. startups and established companies in the perovskite area. The founding members of the board are six U.S. industry players: BlueDot Photonics, Energy Materials Corp., First Solar, Hunt Perovskites Technologies, Swift Solar and Tandem PV.

US-MAP capability providers will share research and development, validation, and pilot manufacturing capability and experience, which should reduce development costs and times to minimize technology risks for potential investors. The main focus areas of the consortium include durability, development of advanced analytical tools, scalable manufacturing tools, in-line metrology and more with each partner providing capabilities according to their areas of strength. The commercial members will have access to the array of research facilities at the four founding members or other capability-providing institutions.

The organizers and members of US-MAP have already begun expanding this network to include the University of Colorado at Boulder and the SLAC National Accelerator Laboratory.

The founding organizers of the US-MAP consortium will explore funding from a variety of sources, including industrial members and the federal government.

Leadership of the consortium will be provided at NREL by Dr. Joseph J. Berry, senior scientist and perovskite team lead, and Dr. Jao van de Lagemaat, director of the Chemistry and Nanoscience Center, who will work with the key points of contact of the other founding member institutions and industrial advisory board.

“Forming this collective will enable innovation in the U.S. that will strengthen our position in these important materials and associated technologies,” Berry said.

For more information about US-MAP, visit the NREL website.

NREL is the U.S. Department of Energy’s primary national laboratory for renewable energy and energy efficiency research and development. NREL is operated for the Energy Department by the Alliance for Sustainable Energy LLC.

UToledo to Maintain Critical Research Operations Only

The University of Toledo, in adherence to the Ohio Department of Health’s recent Stay at Home Order, will restrict research operations to critical research and related essential functions beginning Tuesday, March 24.

Critical research is defined as activity that if discontinued would generate significant data and sample loss; pose a safety hazard; or negatively impact the patient’s care. This includes coronavirus-related activity that has a timeline for deployment that could address the crisis and activity in support of essential human subject research. In addition, this also includes activity that maintains critical equipment in facilities and laboratories; critical samples, reagents and materials; animal populations; and critically needed plant populations, tissue cultures, bacteria, archaea and other living organisms.

Last week UToledo researchers were advised to begin planning for significant disruptions to routine operations. Those plans identified critical research functions and associated essential research personnel for those functions.

From UToledo to NASA, Recent Graduate’s Discovery Sheds New Light on Newborn Stars

Making her dreams come true, a recent graduate of The University of Toledo’s physics program is in the midst of a sky-rocketing year.

Dr. Nicole Karnath earned her Ph.D. last summer and quickly moved to California to serve as instrument scientist at the SOFIA Science Center, which is based in NASA Ames Research Center, where she flies regularly aboard the world’s largest airborne observatory.

Dr. Nicole Karnath, UToledo alumna and instrument scientist at the SOFIA Science Center in California, stands in front of SOFIA, the world’s largest airborne observatory.

On top of her already soaring career success, this week the Astrophysical Journal published Karnath’s research completed while she was a UToledo student, sharing her discovery that reflects a new understanding of what happens at the early stages of star formation.

She credits her student research and the support of her advisor, Dr. Tom Megeath, UToledo astronomy professor, for the job offer from NASA before she had her diploma.

“I am very happy. I enjoy the science, and I love studying the universe,” Karnath said. “Astronomy is an international, collaborative field because we’re working on telescopes all over the world and taking in huge amounts of data. The opportunities are there for students to break in. UToledo astronomy professors know so many people all over the world. Take advantage of their expertise, connections and need for help analyzing data. That’s how I ended up here.”

“Nicole made one of the most exciting discoveries to come out of our UToledo star formation group,” Megeath said. “Just as a talent agent’s biggest dream is to find the actor or actress who will become the next star, for an astronomer, the dream is to find the blob of gas that’s in the process of becoming a star. Nicole has found four such blobs — collapsing gas clouds that are in the first 6,000 years of forming what is called protostar. In ‘star years,’ this is the first 30 minutes of their lives.”

While a graduate student at UToledo, Karnath was part of an international team of astronomers who used two of the most powerful radio telescopes in the world to create more than 300 images of planet-forming disks around very young stars in the Orion molecular clouds.

Pointing both the Very Large Array (VLA) and the Atacama Large Millimeter/submillimeter Array (ALMA) to the region in space where many stars are born, the result is the largest survey to date of young stars, called protostars, and their protoplanetary disks, or planets born in rings of dust and gas.

Among the hundreds of survey images, four protostars looked different than the rest and caught Karnath’s attention.

“These newborn stars looked very irregular and blobby,” Karnath said. “We think that they are in one of the earliest stages of star formation and some may not even have formed into protostars yet.”

It is significant that the scientists discovered four of these objects, which Karnath estimates to be younger than 10,000 years old.

“We rarely find more than one such irregular object in one observation,” said Karnath, who used these four infant stars to propose a schematic pathway for the earliest stages of star formation.

To be defined as a typical protostar, stars should not only have a flattened rotating disk surrounding them, but also an outflow — spewing away material in opposite directions — that clears the dense cloud surrounding the stars and makes them optically visible. This outflow is important because it prevents stars from spinning out of control while they grow. But when exactly these outflows start to happen is an open question in astronomy.

One of the infant stars in this study, called HOPS 404, has an outflow velocity of only 2 kilometers per second, or 1.2 miles per second. A typical protostar outflow has a range of 10 to 100 kilometers per second, or 6 to 62 miles per second.

“It is a big puffy sun that is still gathering a lot of mass, but just started its outflow to lose angular momentum to be able to keep growing,” Karnath said. “This is one of the smallest outflows that we have seen, and it supports our theory of what the first step in forming a protostar looks like.”

“These very young protostars don’t match existing theory very well, meaning that we still have a lot to learn from future studies,” Megeath said.

This schematic shows a proposed pathway, top row, for the formation of protostars, based on four very young protostars, bottom row, observed by Very Large Array (orange) and Atacama Large Millimeter/submillimeter Array (ALMA) (blue). Step 1 represents the collapsing fragment of gas and dust. In step 2, an opaque region starts to form in the cloud. In step 3, a hydrostatic core starts to form due to an increase in pressure and temperature, surrounded by a disk-like structure and the beginning of an outflow. Step 4 depicts the formation of a class 0 protostar inside the opaque region, which may have a rotationally supported disk and more well-defined outflows. Step 5 is a typical class 0 protostar with outflows that have broken through the envelope — making it optically visible — an actively accreting, rotationally supported disk. In the bottom row, white contours are the protostar outflows as seen with ALMA. This image is courtesy of ALMA (ESO/NAOJ/NRAO), N. Karnath, and NRAO/AUI/NSF, B. Saxton and S. Dagnello.

Karnath’s stellar work continues in California at the SOFIA Science Center. SOFIA is a flying observatory made out of a modified Boeing 747, capable of making observations that are impossible for even the largest and highest ground-based telescopes.

SOFIA, which stands for Stratospheric Observatory for Infrared Astronomy, is a partnership of NASA and the German Aerospace Center and under contract with the Universities Space Research Association.

As an instrument scientist, Karnath is responsible for one of five instruments rotated on and off the telescope on the plane, depending on the type of data astronomers are looking to gather.

“I work on an instrument called FORCAST. It’s an imaging instrument and also a spectrometer,” Karnath said. “I’m up there making sure we’re getting the filters needed or the different wavelengths, or looking at a certain target for the right amount of time, and also troubleshooting issues.”

Karnath also is using SOFIA to continue her own research. She submitted a proposal and was awarded observation time on SOFIA scheduled for February 2021.

The curiosity and determination that first fueled her journey as a little girl still powers this successful woman in science today.

“My dad was an amateur astronomer who had a telescope and regularly had me looking at Saturn or a meteor shower,” Karnath said. “I thought astronomy was the most fascinating subject I ever studied. In high school I enjoyed physics and learned that you could make a living off of this. I never looked back, and I’m so lucky that I still love it.”

Karnath said she couldn’t have accomplished so much so soon without the support of Megeath, the UToledo astronomy program, and past advisors at Lowell Observatory and Ohio State University.

“The best part of my job is handing over astronomical data from a cutting-edge observatory, such as the Spitzer Space Telescope, Hubble Space Telescope, ALMA, or the Lowell Discovery Telescope, to a graduate student and seeing the discoveries they make from the data. They never know exactly what they will find,” Megeath said.

“In Nicole’s case, she did an extraordinary job working with an international team spanning three continents and involving universities and institutes across the U.S., Chile and Spain. She combined data from two of the most powerful radio telescopes on Earth to discover these objects. The exciting part is that every discovery brings new mysteries to solve.”

Prior to UToledo, Karnath earned a master’s in applied physics from Northern Arizona University and a bachelor’s in physics and astronomy from Ohio State University.

UToledo is a member of the Association of Universities for Research in Astronomy, a prestigious consortium of 47 U.S. institutions and three international affiliates that operates world-class astronomical observatories for the National Science Foundation and NASA.

Vaccine Researchers Awarded $2.3 Million to Explore Preventing Drug-Resistant Infection

A multidisciplinary research group at The University of Toledo has been awarded $2.3 million from the National Institutes of Health (NIH) to develop a vaccine against a bacterial infection that, once established, is nearly impossible to eradicate.

Pseudomonas aeruginosa is a common bacterium that is generally harmless to healthy individuals. However, in people with compromised immune systems or specific conditions such as cystic fibrosis, it can be deadly.

Dr. Katherine Wall, professor and chair of medicinal and biological chemistry, and Dr. Steven Sucheck, professor of chemistry and biochemistry, have received a $2.3 million from the National Institutes of Health to develop a vaccine for Pseudomonas aeruginosa.

Chronic lung infections, including those caused by drug-resistant Pseudomonas aeruginosa, are the leading cause of death in cystic fibrosis. For example, 60% of individuals with cystic fibrosis experience such an infection, which is often chronic and leads to serious morbidity or mortality. In addition, ventilator-associated pneumonia represents a serious, and often deadly, hospital-acquired infection most commonly caused by infections from the bacterium.

“Pseudomonas, and many other bacteria, are becoming increasingly resistant to even the best currently available antibiotics. It’s a major source of hospital-acquired infections and has a high mortality rate,” said Dr. Katherine Wall, professor and chair of the UToledo Department of Medicinal and Biological Chemistry in the College of Pharmacy and Pharmaceutical Sciences, and principal investigator on the NIH grant. “The infection is very hard to get rid of once it gets established.”

The Word Health Organization recently placed the bacterium among the most critical antibiotic-resistant pathogens, particularly because of the threat it poses in healthcare settings. In the United States alone, more than 32,000 infections of multidrug-resistant Pseudomonas aeruginosa occurred in hospitalized patients in 2017, causing an estimated 2,700 deaths. Thousands more deaths occurred worldwide. In addition to lung infections, Pseudomonas aeruginosa can cause serious blood infections.

Researchers have been working on vaccines targeting the bacterial infection for decades, but as development of new antibiotics lags, preventing the infection has taken on a new urgency.

A 2016 report commissioned by the British government, for example, found antimicrobial resistance could cause up to 10 million annual deaths and cost $100 trillion in economic damages by the year 2050.

The five-year NIH grant, which comes through the National Institute of Allergy and Infectious Diseases, will fund UToledo research aimed at developing new methods for creating synthetic vaccines and a workable vaccine that could protect against Pseudomonas aeruginosa.

“There have been many attempts to make protein and carbohydrate vaccines. One thing that is unique about this project is that we are combining well-defined organism-specific carbohydrate antigens with organism-specific protein antigens,” said Dr. Steven Sucheck, professor in the Department of Chemistry and Biochemistry in the College of Natural Sciences and Mathematics, and lead principal investigator on the grant.

Antigens are the toxins from a bacteria or virus that trigger the body’s immune response.

“In this work, we combine a synthetic carbohydrate antigen with organism-specific protein antigens to increase the antigen coverage,” Sucheck said. “If the strategy is successful, it greatly expands the potential applications of synthetic carbohydrates in vaccines.”

Many of the common vaccines we receive in childhood, such as chicken pox and polio, are manufactured with dead, weakened or altered pathogens to generate immunity to the infection.

Synthetic carbohydrate vaccines instead use complex chemistry to create well-defined carbohydrate antigens that can be conjugated with proteins to create a vaccine.

Sucheck and Wall have been collaborating on vaccine development for more than a decade, beginning with a project to develop synthetic vaccines to help the body’s natural immune system better engage against cancer cells.

The new Pseudomonas aeruginosa project, which also includes Dr. Erin Prestwich, assistant professor in the Department of Medicinal and Biological Chemistry, is a significant expansion of that, taking the basic vaccine development platform and shifting its target to bacteria rather than tumor cells.

Sucheck also is working on discovering new drugs to fight tuberculosis, another bacterial infection that is becoming increasingly difficult to treat because of antibiotic resistance. In 2018, he and a former colleague now at the University of Nebraska received a five-year, $2.1 million NIH grant to continue their work.

“There’s an expertise in the lab related to carbohydrates that we’re trying to leverage in different ways. You can use them to make vaccines, or we can try to target bacteria such as Mycobacterium tuberculosis with small molecules. That’s the broader theme that runs through my work,” Sucheck said. “We’re always trying to do work that’s impactful and addresses an urgent need. New approaches to treating drug-resistant bacteria is one of those urgent needs.”

Researchers Seek New Treatment for Sepsis Through Innovative Approach

New research from The University of Toledo College of Medicine and Life Sciences suggests it may be possible to treat septic shock with drugs that are already part of the clinical repertoire.

Screening existing pharmaceutical agents for unexpected applications is increasingly seen as a valuable tool for establishing new treatments, particularly within the field of oncology research.

Pan

Dr. Kevin Pan, professor and chair of the UToledo Department of Medical Microbiology and Immunology, is applying that innovative approach to sepsis, a life-threatening condition in which the body’s extreme immune response to infection damages its own organs.

“Severe sepsis is a big problem in the clinic,” Pan said. “There are about 750,000 annual cases in the U.S. alone, and we do not have very effective treatments beyond targeting the original infection with antibiotics. We are hoping to find new ways within our existing drug library to regulate the immune response and directly treat sepsis.”

By focusing on existing drugs, researchers hope to advance therapies more quickly and with less cost than the novel drug discovery process.

Pan and his collaborators at Southern Medical University in Guangzhou, China, recently published a study in the journal Scientific Reports that found a drug called rolipram protected mice from E. coli induced septic shock.

“Our research shows rolipram can reduce inflammatory cytokine production and increase mouse survival. This suggests rolipram might be a novel therapeutic agent for fighting against sepsis in the clinical setting,” Pan said.

Rolipram was originally developed as an anti-depressant and has been studied for a number of other potential applications, including chronic obstructive pulmonary disease. Pan’s team is the first to show it might protect against sepsis.

Treatment for sepsis is largely limited to flooding the body with antibiotics and fluids. However, the growing problem of antibiotic resistance means many bacterial infections can be difficult to kill, allowing the body’s overheated immune response to go on unchecked.

By exploring new ways to modulate that immune response, Pan and his collaborators hope to provide a complimentary treatment to go along with antibiotics that can prevent damage to critical organ systems.

“This is early stage research, and rolipram is known to have difficult side effects. However, our work proves the potential of repurposing drugs to treat septic shock,” Pan said. “We plan to continue working with rolipram, and are beginning tests on a number of other drugs.”

New Biomarker Could Better Predict Diabetic Kidney Disease

Clinicians may soon have a better way to predict which of their diabetic patients are most likely to develop kidney disease, allowing for earlier interventions that keep patients off lifelong dialysis or transplant waiting lists.

In a study led by Dr. Rujun Gong, professor and director of kidney research at The University of Toledo College of Medicine and Life Sciences, researchers analyzed how an enzyme present in urine can be used as a novel biomarker for diabetic kidney disease progression.

Gong

The study was published in the journal Kidney International.

“The research in this field is very important,” Gong said. “There is a pressing need to more precisely determine which diabetic patients are at the highest risk, as early intervention and intensive treatment can prevent this certain cohort of patients from developing diabetic kidney disease and kidney failure.”

Diabetic kidney disease is the No. 1 cause of kidney failure in the United States, accounting for nearly half of all new cases, according to the National Kidney Foundation. Prior research has shown approximately 40% of diabetics will develop kidney disease, but Gong said clinicians lack a reliable way of determining which patients will be affected.

“Right now, testing patients for albuminuria, or protein in the urine, is considered by some as a gold standard diagnostic,” Gong said. “However, in the field of nephrology practice, there is a huge debate about the test’s usefulness. There is evidence suggesting it is not accurate.”

By examining cell culture and animal models and performing a retrospective study of diabetic patients in China, Gong and his collaborators from the Brown University School of Medicine and Zhengzhou University concluded that an over-activation of an enzyme called GSK3-beta was strongly linked to the progression of diabetic kidney disease, and a better indicator of disease development than albuminuria.

GSK3-beta plays a key role primarily in the insulin pathway, helping the body transform glucose — or sugar — into glycogen — or stored energy — and back again. The enzyme is also pivotal for other cellular processes and can be measured in urine because it is present in cells shed from the kidney.

“The idea here is to take advantage of these exfoliated cells as a liquid biopsy,” Gong said. “It’s not painful. It’s not invasive. We can simply collect the urine and examine the exfoliated kidney cells as a biomarker.”

The incidence rate of diabetes has risen sharply. The U.S. Centers for Disease Control and Prevention notes the percentage of Americans living with diabetes rose from 4.4% in 2000 to 7.4% in 2015, while the World Health Organization says the number of people with diabetes has risen from 108 million in 1980 to 422 million in 2014.

As the number of people with diabetes continues to grow, Gong said it is important to give clinicians new tools to keep their patients healthy. If a physician knows a diabetic patient is prone to developing kidney disease, they can take steps to reduce the risk by ensuring tighter glycemic control, strictly monitoring blood pressure, avoiding nephrotoxic drugs, and prescribing other protective medications.

Beyond being a biomarker, GSK3-beta may be a therapeutic target itself, as it is implicated in a number of kidney conditions. Previous research by Gong under the support of the National Institutes of Health grant found that very small doses of lithium, frequently used as a medication for conditions such as bipolar affective disorder, can inhibit GSK3-beta and accelerate the recovery of renal function.

The next step for researchers is to conduct a large-scale randomized study to further confirm the ability of GSK3-beta to predict diabetic kidney disease.

UToledo Law Scholar’s New Book ‘Originalism’s Promise’ Illuminates Constitution

In the midst of President Donald Trump’s impeachment trial and heading into the 2020 presidential election, a constitutional law scholar at The University of Toledo released a new book providing the first natural law justification for an originalist interpretation of the American Constitution.

In “Originalism’s Promise: A Natural Law Account of the American Constitution” published by Cambridge University Press, Lee Strang, John W. Stoepler Professor of Law and Values in the UToledo College of Law, provides a summary of the history of constitutional interpretation in the United States and writes a thorough and detailed description of how originalism operates in practice.

Strang

“This book provides an argument for how Americans should interpret the Constitution and offers a way out of the bitterness exemplified by the confirmation hearings for Supreme Court Justice Brett Kavanaugh,” Strang said. “Faithfulness to the Constitution’s original meaning is supported by sound reasons, reasons that help all Americans achieve their own human flourishing.”

The College of Law is celebrating the book’s release with a book launch that features a lecture by Strang Wednesday, Jan. 29, at noon in the Law Center McQuade Auditorium. The free, public event will be followed by a book signing.

Strang, who was a visiting fellow at the James Madison Program at Princeton University during the 2018-19 academic year, has published dozens of articles in the fields of constitutional law and interpretation; property law; and religion and the First Amendment.

“In this presidential election year, my goal is to inform Americans as they debate the Supreme Court’s future,” Strang said. “‘Originalism’s Promise’ is the product of more than 20 years of thinking through two common American commitments. First, Americans strive to be faithful to our Constitution. Second, and following the Declaration of Independence, many Americans are committed to some version of natural law. Together, these commitments suggest that Americans of all stripes should utilize originalism to interpret our common Constitution.”

The UToledo College of Law awarded Strang the Faculty Scholarship Award in 2019 for “Originalism’s Promise.” He was the recipient of The University of Toledo Outstanding Faculty Research and Scholarship Award in 2017.

In 2015, Strang served as a visiting scholar at the Georgetown Center for the Constitution.

Strang said the inspiration for writing the book stems from his experiences as a younger person attending political events with his parents, his education as a law student, and how vigorously Americans disagree about how to interpret the Constitution.

“I listened as politicians and activists argued that the Constitution supported their positions, so this book grew out of an attempt to identify how Americans can ascertain which claims are correct,” Strang said. “Also, as a student taking constitutional law classes, we did not study the Constitution’s text, structure and history. I remember we nearly always read Supreme Court opinions, which themselves rarely paid attention to the Constitution’s text. This book both criticizes and supports aspects of that educational approach.”

Study Examines Attitudes Toward Transgender Athletes

As several states draft legislation that would force student-athletes to play as their gender identified on their birth certificate instead of on a team that matches their gender identity, a team of political scientists investigated underlying factors that drive public opinion on transgender athletes.

The new study shows while women in general are more supportive than men of transgender athletes participating in sports by gender identity instead of biological sex, women who are sports fans are more likely to oppose it, holding views that resemble male sports fans.

The research recently published in the journal Sex Roles investigated public attitudes toward the participation of transgender people in sports by using data from a 2015 survey of 1,020 adults across the U.S.; the data was previously used by the same researchers to analyze public opinion on a variety of transgender rights issues.

Dr. Jami Taylor, professor of political science and public administration at The University of Toledo who focuses on transgender politics and policy, is part of the team who found that attitudes about transgender athletes are strongly shaped by an individual’s characteristics, political values and personality traits.

Also, the study shows people who have contact with transgender, gay and lesbian people, as well as those with stronger egalitarian attitudes, are more favorable toward transgender participation, whereas those with high moral traditionalism are more opposed.

“This is a very complicated area, and there are legitimate concerns about fairness for both transgender athletes and those who are not transgender,” said Taylor, author of the 2017 book “The Remarkable Rise of Transgender Rights.” “We need to have thoughtful policies that ensure fair competitions, but also ensure that transgender athletes aren’t discriminated against. As governments, nonprofits and businesses begin to craft policies that decide how and with whom transgender athletes will compete in sports, they need to avoid one-size-fits-all solutions because of the complexity of the issues.”

“Given the gendered nature of sports and the resistance to the issue among sports fans — both male and female — policymakers will likely need to tread carefully and should have a care in this area as they craft policy solutions. Our work might be helpful to inform policymakers, as well as advocates who promote inclusion.”

Research contributors include Taylor; Dr. Andrew Flores, assistant professor in the Department of Government at American University and lead author of the study; Dr. Donald Haider-Markel, professor and chair of the Department of Political Science at the University of Kansas; Dr. Daniel Lewis, associate professor of political science at Siena College; Dr. Patrick Miller, associate professor in the Department of Political Science at the University of Kansas; and Dr. Barry Tadlock, professor of political science at Ohio University.

Current policy depends on the position of governing bodies, such as the NCAA at the collegiate level, and applicable laws that may vary by location. For instance, California law requires that transgender students be treated according to their gender identity, not biological sex.

The issue, according to lawmakers proposing new legislation in New Hampshire, Washington, Georgia, Tennessee and Missouri, is whether transgender-rights protections are leading to unfair competition in women’s sports, referencing male-to-female transgender students and arguing they have natural physical advantages over biological females.

However, the study cited a female-to-male case: Mack Beggs’ victory in the Texas Class 6A girls’ state wrestling championship in 2017, even though the female-to-male transgender student started his transition two years prior and took testosterone injections.

“It was a ridiculous situation. He wanted to wrestle with the boys and received harsh treatment from fans when he was forced to compete with girls,” Taylor said. “Due to his success, parents accused him of cheating, but the rule in Texas was he had to compete according to the gender on his birth certificate, which was a girl. If he was in California, he would’ve competed against boys.”

The study finds that 35.6% of women agreed with allowing transgender athletes to participate in sports aligned with their gender identity, compared to 23.2% of men.

As the 2020 Olympic games in Tokyo approach, Taylor calls the Olympics reasonably inclusive to transgender athletes and commends the International Olympic Committee for its attention to both human rights and fair competition.

“The International Olympic Committee no longer requires transgender athletes to have had surgery, but there is a strict requirement around hormonal management,” Taylor said. “It’s far less restrictive for female-to-male athletes than for male-to-female athletes, which seems to be a reasonable attempt to grapple with this complex issue. Importantly, the IOC’s approach looks at evidence in this evolving area.”

Growth of Craft Beer Linked to Record Number of States Harvesting Hops

Tasting terroir, or a sense of place, isn’t only reserved for wine lovers drinking a glass of burgundy or champagne from France.

It’s evident, too, in the U.S. craft beer boom and the growing preference for local hops.

Reid

Hops, a key ingredient in making beer, is a crop making a comeback on farms across the country thanks to the incredible rise of the craft brewing industry over the past decade.

Craft breweries and their customers’ thirst for new, locally grown flavors are playing a big role in fueling an unprecedented geographic expansion of hop production across the U.S., according to researchers at The University of Toledo and Penn State University.

Their findings, which were recently published in the Journal of Wine Economics, suggest that as more craft breweries emerge around the country, so may new opportunities for farmers.

“It is fantastic to see the re-emergence of hop production in states which, at one point, had abandoned the crop,” said Dr. Neil Reid, professor of geography and planning at The University of Toledo, who teaches a class titled The Geography of Beer and Brewing. “Hops provide aroma and bittering characteristics in beer. Looking to differentiate themselves from Molson Coors and Anheuser Busch, independent craft brewers demand locally grown hops, experiment with different varieties of hops, and use more hops in beer production compared to mass-produced beers.”

According to the Brewers Association, between 2007 and 2017, the number of breweries in the U.S. increased from 1,459 to 6,490.

The researchers found that the number of breweries in a state is associated with more hop farms and hop acres five years later. The number of hop farms grew from 68 to 817, and hop acreage expanded from 31,145 to 59,429 acres.

Before 2007, hop production in the country was limited to only three Pacific Northwest states—Oregon, Washington and Idaho. Hops are now produced in 29 states, according to the Hop Growers of America.

“Our study is the first to systematically show that the number of hop farms in a state is related to the number of craft breweries,” said Claudia Schmidt, assistant professor of agricultural economics in Penn State’s College of Agricultural Sciences. “It suggests that in areas where hop production is possible and not cost-prohibitive, breweries are expanding markets for farmers and providing an opportunity to diversify farm income.”

In fact, the growth positioned the U.S. as the largest producer of hops globally, both in terms of acreage and production.

Working with farm, brewery and climate data, the researchers developed a statistical model to determine whether new craft breweries in a state between 2007 and 2017 resulted in a larger number of hop producers and hop acres planted, by both new and existing growers in that state. They built a time lag into their model to identify the effect of new breweries over time. They also controlled for other variables that may influence farmers to start growing hops, such as average farm size, average net farm income and climate.

Their findings are correlational and do not point to a clear cause and effect. However, the time lag built into the model indicates that the growth in breweries preceded the growth in hop farms.

If more brewers are looking for hops grown nearby, then more farmers may be willing to try growing them, even if only on a small scale. For instance, in Pennsylvania, only 17 farms reported hop production in 2017, and their combined acreage is small — only 21 acres in all, according to the U.S. Census of Agriculture.

In contrast, in 2017, there were 100 acres of farmland devoted to hop production in Ohio. According to the Ohio Hop Growers Guild, there are more than 70 farms in Ohio that are growing hops.

While the growing of hops in states like Ohio and Pennsylvania is a relatively recent phenomenon, many Midwestern and Northeastern states have historical connections to the hop industry.

“In 1870, the three leading hop-producing states were New York, Wisconsin and Michigan,” Reid said. “A number of factors, including declining yields, disease outbreaks, high production and processing costs, and an inability to achieve economies of scale, contributed to the decline and disappearance of the hop industry in the Midwest and Northeast.”

Reid, who is affectionately known as “The Beer Professor,” is an expert on the craft brewing industry and its economic geography. His research is focused on the industry’s growth in the U.S. and its potential role in helping to revitalize neighborhood economies.

His previous research found that the craft brewery boom is good for home values. That study showed single-family homes in the city of Charlotte, N.C., saw their value increase by nearly 10% after a brewery opened within a half mile of the property, and center-city condos got a nearly 3% bump.

Reid will give the opening keynote address at the 2020 Beer Marketing and Tourism Conference Wednesday, Feb. 5, in St. Petersburg, Fla.

His new book titled “Agritourism, Wine Tourism, and Craft Beer Tourism: Local Responses to Peripherality Through Tourism Niches” will be published later this month. The book is co-edited with Maria Giulia Pezzi and Alessandra Faggian of the Gran Sasso Science Institute in L’Aquila, Italy.