Publisher Health

Tiny nets woven from DNA strands can ensnare the spike protein of the virus that causes COVID-19, lighting up the virus for a fast-yet-sensitive diagnostic test — and also impeding the virus from infecting cells, opening a new possible route to antiviral treatment, according to a new study.
Researchers at the University of Illinois Urbana-Champaign and collaborators demonstrated the DNA nets’ ability to detect and impede COVID-19 in human cell cultures in a paper published in the Journal of the American Chemical Society.
“This platform combines the sensitivity of PCR and the speed and low cost of antigen tests,” said study leader Xing Wang, a professor of bioengineering and of chemistry at Illinois. “We need tests like this for a couple of reasons. One is to prepare for the next pandemic. The other reason is to track ongoing viral epidemics — not only coronaviruses, but also other deadly and economically impactful viruses like HIV or influenza.”
DNA is best known for its genetic properties, but it also can be folded into custom nanoscale structures that can perform functions or specifically bind to other structures much like proteins do. The DNA nets the Illinois group developed were designed to bind to the coronavirus spike protein — the structure that sticks out from the surface of the virus and binds to receptors on human cells to infect them. Once bound, the nets give off a fluorescent signal that can be read by an inexpensive handheld device in about 10 minutes.
The researchers demonstrated that their DNA nets effectively targeted the spike protein and were able to detect the virus at very low levels, equivalent to the sensitivity of gold-standard PCR tests that can take a day or more to return results from a clinical lab.
The technique holds several advantages, Wang said. It does not need any special preparation or equipment, and can be performed at room temperature, so all a user would do is mix the sample with the solution and read it. The researchers estimated in their study that the method would cost $1.26 per test.

New UMBC-led research in Frontiers in Microbiology suggests that viruses are using information from their environment to “decide” when to sit tight inside their hosts and when to multiply and burst out, killing the host cell. The work has implications for antiviral drug development.
A virus’s ability to sense its environment, including elements produced by its host, adds “another layer of complexity to the viral-host interaction,” says Ivan Erill, professor of biological sciences and senior author on the new paper. Right now, viruses are exploiting that ability to their benefit. But in the future, he says, “we could exploit it to their detriment.”
Not a coincidence
The new study focused on bacteriophages — viruses that infect bacteria, often referred to simply as “phages.” The phages in the study can only infect their hosts when the bacterial cells have special appendages, called pili and flagella, that help the bacteria move and mate. The bacteria produce a protein called CtrA that controls when they generate these appendages. The new paper shows that many appendage-dependent phages have patterns in their DNA where the CtrA protein can attach, called binding sites. A phage having a binding site for a protein produced by its host is unusual, Erill says.
Even more surprising, Erill and the paper’s first author Elia Mascolo, a Ph.D. student in Erill’s lab, found through detailed genomic analysis that these binding sites were not unique to a single phage, or even a single group of phages. Many different types of phages had CtrA binding sites — but they all required their hosts to have pili and/or flagella to infect them. It couldn’t be a coincidence, they decided.
The ability to monitor CtrA levels “has been invented multiple times throughout evolution by different phages that infect different bacteria,” Erill says. When distantly related species demonstrate a similar trait, it’s called convergent evolution — and it indicates that the trait is definitely useful.

Our guts, and all our organs, are arranged in left-right asymmetric patterns inside our bodies, so that everything may fit.
At the same time, development of organs such as the intestine is anything but haphazard. In healthy embryos, rotation of the gut during development always occurs in a counterclockwise direction and is perfectly timed. It’s a complicated process that scientists have long worked to understand.
Now, a study published Sept. 23 in the journal Science finds that gut rotation during development is orchestrated by two waves of expression of a transcription factor called Pitx2. The second wave, it turns out, is triggered by mechanical cues within an elastic tissue that anchors the gut tube, and later becomes a conduit for blood and lymphatic vessels that supply the gut tube.
The findings have important implications for understanding the basic mechanisms of how organs form, which could aid efforts to diagnose and prevent birth defects, such as intestinal malrotation and volvulus, where developing intestines become twisted and strangle themselves.
“The entire gastrointestinal tract is one tube that absorbs all of our nutrients, and it’s giant, so it has to loop to fit inside our body,” said Natasza Kurpios, associate professor of molecular medicine in the College of Veterinary Medicine and senior author of the study. Bhargav D. Sanketi, a doctoral student in Kurpios lab, is the paper’s first author.
“What we found years ago is that looping is highly conserved and it’s very, very regulated,” Kurpios said.
It turns out that organs such as the heart, liver, lungs and gut (intestines) are all asymmetrically situated — found on one side of the body, or spanning the left and right, but not centered. Understanding how the gut forms with left-right asymmetry could reveal patterns of development found in other organs, such as the heart.
Previous work has shown that a gene called Nodal induces the first wave of Pitx2 to establish the early body plan. But Nodal’s presence is short-lived, and once it stimulates Pitx2 expression, it disappears before gut rotation occurs. So, for a long time it has been unknown how Pitx2 stays active to direct gut rotation when Nodal is gone. “Our first surprise was that Pitx2 expression actually goes away and then it comes back as the gut tube is ready to loop,” Kurpios said. “And so the question was, what wakes Pitx2 up?”
The researchers found that a sensor, TGF-beta, lies latent until it gets activated by mechanical forces. In the case of the gut, this is dictated by the dorsal mesentery which attaches to and holds the gut tube in place. To direct rotation, the dorsal mesentery tissue dramatically expands on the right side and compacts on the left. When it does so, TGF-beta senses these changing forces and activates expression of a second wave of Pitx2, which stimulates gut tube looping. In other words, the wave of Pitx2 that establishes body asymmetry is different from the wave that rotates the gut.
In the study, the researchers used engineered mice and chicken embryos, which allow Kurpios and colleagues to open a little window in the egg shell so they can view development and manipulate gene expression.
The lab of co-author Jan Lammerding, professor in the Meinig School of Biomedical Engineering, used a probe in live embryos to measure stiffness and elasticity in the dorsal mesentery. The measurements revealed expansion on the right side and TGF-beta-Pitx2 induced braking of that expansion on the left side, which created the perfect amount of tilt in the tissue for proper gut tube looping.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases; the March of Dimes; the National Heart, Lung and Blood Institute; the Volkswagen Foundation; and the Cornell Center for Vertebrate Genomics.
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Materials provided by Cornell University. Original written by Krishna Ramanujan, Cornell Chronicle. Note: Content may be edited for style and length.

Children who were infected with COVID-19 show a substantially higher risk of developing type 1 diabetes (T1D), according to a new study that analyzed electronic health records of more than 1 million patients ages 18 and younger.
In a study published today in the journal JAMA Network Open, researchers at the Case Western Reserve Univesity School of Medicine report that children and adolescents who contracted COVID-19 were more prone to developing T1D in the six months following their COVID diagnosis.
The findings showed a 72% increase in new diagnoses of T1D in COVID-19 patients 18 years old and younger — although the research emphasized that it is unclear whether COVID-19 triggers new onset of T1D.
About 187,000 children and adolescents younger than 20 live with T1D nationally, according to the Centers for Disease Control and Prevention (CDC).
“Type 1 diabetes is considered an autoimmune disease,” said Pamela Davis, Distinguished University Professor and The Arline H. and Curtis F. Garvin Research Professor at the Case Western Reserve School of Medicine, a study corresponding author. “It occurs mostly because the body’s immune defenses attack the cells that produce insulin, thereby stopping insulin production and causing the disease. COVID has been suggested to increase autoimmune responses, and our present finding reinforces that suggestion.”
The team analyzed the de-identified electronic health records of nearly 1.1 million patients age 18 years and younger in the United States and 13 other countries diagnosed with the SARS-CoV-2 infection between March 2020 and December 2021 and also those diagnosed with a non-COVID-related respiratory infection during that same period.

Imperial researchers have embedded new low-cost sensors that monitor breathing, heart rate, and ammonia into t-shirts and face masks.
Potential applications range from monitoring exercise, sleep, and stress to diagnosing and monitoring disease through breath and vital signs.
Spun from a new Imperial-developed cotton-based conductive thread called PECOTEX, the sensors cost little to manufacture. Just $0.15 produces a metre of thread to seamlessly integrate more than ten sensors into clothing, and PECOTEX is compatible with industry-standard computerised embroidery machines.
First author of the research Fahad Alshabouna, PhD candidate at Imperial’s Department of Bioengineering, said: “The flexible medium of clothing means our sensors have a wide range of applications. They’re also relatively easy to produce which means we could scale up manufacturing and usher in a new generation of wearables in clothing.”
The research team embroidered the sensors into a face mask to monitor breathing, a t-shirt to monitor heart activity, and textiles to monitor gases like ammonia, a component of the breath that can be used to track liver and kidney function. The ammonia sensors were developed to test whether gas sensors could also be manufactured using embroidery.
Fahad added: “We demonstrated applications in monitoring cardiac activity and breathing, and sensing gases. Future potential applications include diagnosing and monitoring disease and treatment, monitoring the body during exercise, sleep, and stress, and use in batteries, heaters, anti-static clothing.”
The research is published today in Materials Today.

Williams-Beuren syndrome (WBS) is a rare disorder that causes neurocognitive and developmental deficits. However, musical and auditory abilities are preserved or even enhanced in WBS patients. Scientists at St. Jude Children’s Research Hospital have identified the mechanism responsible for this ability in models of the disease. The findings were published today in Cell.
Understanding what causes the superior auditory ability in WBS patients may provide a target for treating the disease in addition to helping advance research on the ability to discriminate between sounds. WBS offers insight into the mechanisms that underlie enhanced auditory abilities. For instance, some people with WBS have perfect pitch, which is the ability to differentiate between notes or frequencies without a reference guide.
“WBS stands out among neurodevelopmental disorders because children with the disorder, despite profound learning disabilities, can have a higher prevalence of superior musical and linguistic abilities than children in the general population,” said corresponding author Stanislav Zakharenko, M.D., Ph.D., St. Jude Department of Developmental Neurobiology. “We were fascinated by that and wanted to know more about how a disorder that is caused by a loss of 27 genes could help individuals gain a better than normal ability for auditory processing.”
Excited neurons in the auditory cortex
Mouse models of WBS have an enhanced ability to discriminate between sound frequencies. These mice also have improved frequency coding in the auditory cortex, the part of the brain that processes sound. The researchers showed that the enhanced ability to discriminate between frequencies is caused by hyperexcitable interneurons in the auditory cortex.
To understand the cellular biology that underlies enhanced auditory abilities in WBS patients, the researchers conducted an RNAseq experiment. The data led the researchers to a neuropeptide receptor called VIPR1, which is reduced in the auditory cortex of individuals with WBS. The reduction in VIPR1 was also found in cerebral organoids, advanced models made in the laboratory using human induced pluripotent stem cells.
The scientists found that the transcription factor Gtf2ird1, encoded by one of the 27 genes lost in those with WBS, regulates VIPR1. Deleting or overexpressing VIPR1 in the auditory cortex can mimic or reverse the auditory effects seen in WBS. Thus, it is Gtf2ird1 downregulating VIPR1 that is responsible for the impact of WBS on auditory ability.
“I didn’t know a lot about VIPR1 before it popped up in our data because the role of this family of receptors in the brain is under-appreciated compared to other neuromodulator or neurotransmitter receptors,” said first-author Christopher Davenport, St. Jude Department of Developmental Neurobiology. “Our findings show that they can strongly impact information processing and behavior and are likely relevant for other behaviors and diseases as well.”
“This work suggests that reducing neuronal hyperexcitability might be a general mechanism for treating WBS through targeting VIPR1,” Zakharenko said. “It also opens up new directions to learn about musicality and how our brain differentiates sounds based on these findings in models of WBS.”
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Materials provided by St. Jude Children’s Research Hospital. Note: Content may be edited for style and length.

Fat cells, or adipocytes, that grow in close proximity to breast cancers can shift into other cell types that promote tumor growth, a new study by UT Southwestern researchers suggests. The findings, published in Cell Reports, could lead to new ways to fight breast cancer, a disease that is diagnosed in more than 300,000 U.S. women each year and kills nearly 45,000 annually.
“We identified novel adipocyte-derived cell types in the mammary gland that offer a fertile soil for breast cancer tumor invasion and growth,” said study leader Philipp Scherer, Ph.D., Professor of Internal Medicine and Cell Biology and a member of the Harold C. Simmons Comprehensive Cancer Center at UTSW.
Obesity has long been considered a risk factor for breast cancer occurrence and worse prognosis. Studies have shown that fat cells in close contact with breast tumor cells have an enhanced ability to break down their lipids to provide fuel for invading tumor cells. However, Dr. Scherer explained, it has been unclear what other roles these adipocytes play in breast cancer progression.
To answer this question, Qingzhang Zhu, Ph.D., an Instructor of Internal Medicine and member of the Scherer laboratory, and his colleagues used a genetic technique that “painted” adipocytes in lab mice so they glowed a fluorescent color, making it possible to follow these cells long term. When the researchers implanted breast tumors in the mice or genetically manipulated the rodents’ own breast cells to turn them into tumor cells, they saw that nearby fat cells shrank and took on forms different from native adipocytes. Genetic testing to identify which genes were active in these fat cells showed these cells first regressed to an earlier stage in development, then gradually developed genetic markers of other cell types, including connective tissue cells, muscle cells, and immune cells.
Further investigation showed these changed fat cells encouraged breast cancer tumors to grow. However, this property also depended critically on their ability to supply energy to neighboring tumor cells. In addition, the properties of the cell types that fat cells morph into after they lose their lipids and their fat cell identity are important, since they add significantly to the local fibrosis, which contributes to the stiffness of breast tissue. When the researchers enhanced the lipid-storing capacity of mature fat cells, they ceased to morph into other cell types and no longer promoted tumor growth.
Dr. Scherer said the mechanism for how adipocytes change into other cell types is not yet clear; however, a chemical signal from tumor cells is probably responsible for this phenomenon. He and his colleagues plan to search for this signal and look for other ways to manipulate this system to discourage breast cancer growth.
The study is part of a joint initiative of UTSW’s Touchstone Diabetes Center and Harold C. Simmons Comprehensive Cancer Center to better understand the connection between cancer risk and obesity.
Dr. Scherer holds the Gifford O. Touchstone, Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research and the Touchstone/West Distinguished Chair in Diabetes Research.
Other UTSW researchers who contributed to this study include Yi Zhu, Chelsea Hepler, Qianbin Zhang, Jiyoung Park, Christy Gliniak, Gervaise H. Henry, Clair Crewe, Dawei Bu, Zhuzhen Zhang, Shangang Zhao, Thomas Morley, Na Li, Dae-Seok Kim, Douglas Strand, Yingfeng Deng, Ruth Gordillo, Christine M. Kusminski, and Rana K. Gupta.
This study was supported by National Institutes of Health grants (R01-DK104789, RC2-DK118620, R01-DK55758, R01-DK099110, R01-DK118620, R01-10 DK127274, and R01-131537).

Type 1 diabetes (T1D) is an autoimmune disease in which the pancreas makes little or no insulin. The details on the events that occur during autoimmune destruction of the pancreatic beta-cells have been studied extensively yet the mystery of what causes autoimmunity is unknown. In a new study, researchers from Boston University School of Medicine (BUSM), Indiana University School of Medicine and Temple University School of Medicine, present a testable hypothesis to explain the initiation of autoimmunity. If validated, this would allow early detection and possible prevention of T1D in susceptible individuals.
“Previous studies have focused on the triggers, genes and proteins that differentiate individuals with T1D from those without diabetes with a focus on the b-cell (b-cells create antibodies) as a target of immune destruction and blood glucose as the main abnormality. Our focus is on metabolic communication as an early instigator with the b-cell as an active participant together with the immune cells,” explains corresponding author Barbara Corkey, PhD, professor emeritus of medicine and biochemistry at BUSM.
According to Corkey, her research led her to generate the testable hypothesis that the induction of autoimmunity is a consequence of one or more major inflammatory events in individuals with susceptible human leukocyte antigens (molecule found on the surface of most cells in the body that play an important part in the body’s immune response to foreign substances) phenotypes plus elevated sensitivity to cytokines (substances secreted by certain cells of the immune system) and free fatty acids (FFA).
“Illnesses or environmental agents that dramatically increase cytokine production and/or elevate FFA initiate autoimmune destruction in individuals with specific genetic features. Thus, early prevention should be aimed at decreasing elevated lipids and diminishing excessive simultaneous elevation of cytokines or cytokine- and lipid-induced immune cell proliferation,” she adds.
Corkey believes that the characteristics that make individuals susceptible to autoimmune destruction could also apply to other autoimmune diseases such as toxic shock syndrome and possibly long COVID.
These findings appear online in the journal Diabetes.
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Materials provided by Boston University School of Medicine. Note: Content may be edited for style and length.

A new study by researchers at the Marshall University Joan C. Edwards School of Medicine found that lower initial cortisol levels may serve as a predictor for retention in treatment programs for substance use disorder.
The prospective observational study examined the salivary cortisol, stress exposure, adverse childhood experiences (ACEs) and treatment retention of males enrolled in abstinence-based, residential alcohol and drug recovery programs. Their findings were published last month in Alcoholism: Clinical and Experimental Research, the scientific journal on alcohol abuse and treatment for the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism.
Cortisol levels reflect a physiological response to stress. In this case, researchers found that participants who remained in the treatment program less than 90 days had significantly higher initial cortisol levels than those who remained in the program longer than 90 days. Further, a Cox proportional hazards model indicated that elevated salivary cortisol, marital/relationship status and ACEs score correlated significantly with hazards of discontinuing the program early.
“Our hope is that these findings will lead to cortisol as a biomarker that can help clinicians determine which individuals might need a more intensive therapeutic approach,” said Todd H. Davies, Ph.D., associate director of research and development at the Joan C. Edwards School of Medicine and corresponding author on the study.
Taylor R. Maddox-Rooper, Kristiana Sklioutouskaya-Lopez, Trenton Sturgill, Caroline Fresch, Charles W. Clements II, M.D.; Rajan Lamichhane, Ph.D.; and Richard Egleton, Ph.D., also served as co-authors on the article. The research team also collaborated with Recovery Point of West Virginia, a long-term, residential recovery program based on the peer-driven model of recovery.
The research team, in collaboration with Recovery Point, currently has a larger follow-up study underway that seeks to identify the clinical significant levels of cortisol. This expanded study also includes a more representative population and examine the hormone oxytocin.
This work is supported by a rural grant from the Marshall University Robert C. Byrd Center for Rural Health through the West Virginia Higher Education Policy Commission. 
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Materials provided by Marshall University Joan C. Edwards School of Medicine. Note: Content may be edited for style and length.

A new discovery from the University of Virginia School of Medicine could let doctors ramp up production of blood-clotting platelets on demand, a timely finding following the Red Cross’ declaration earlier this year of a national blood “crisis.” The group labeled it the worst blood and platelet shortage in more than a decade and said it posed a “concerning risk to patient care.”
In addition to making available more lifesaving platelets for transfusion, UVA’s new discovery could help doctors better treat thrombocytopenia, a potentially dangerous clotting disorder that strikes almost a third of newborns in intensive care. The finding also could benefit patients battling cancer who need cord-blood transplants.
“Because of worsening shortages of donor-derived platelet units, there has been a big push within both public and private sectors for cell culture-based methods of generating platelets,” said Adam N. Goldfarb, MD, the chief of UVA’s Division of Experimental Pathology. “In addition to alleviating platelet shortages, the cell culture approach affords the opportunity for creating ‘designer platelets’ — for example, platelets that do not elicit an immune response, which is a major problem in cancer patients.”
Understanding Platelet Production
The new findings offer important insights into platelet-producing cells called megakaryocytes and how they change between birth and adulthood. In babies, megakaryocytes are much better at proliferating — making more megakaryocytes — than they are at making platelets. It’s like they’re focused on building platelet-production factories. With time, the megakaryocytes begin cranking out platelets in great volume, but this is accompanied by a dramatic slowdown in the production of megakaryocytes. So platelet numbers go up, but the ability to create new “factories” slows to a crawl.
Goldfarb and his team found they could toggle megakaryocytes between their infant and adult modes — between making factories or making platelets — by blocking a particular enzyme, Dyrk1a. Need more factories? No problem. That could relieve a major bottleneck in the production of platelets outside the body for transfusion.
Further, the finding could benefit cancer patients who receive cord-blood transplants by helping overcome platelet problems that slow the immune system’s recovery and raise the risk of dangerous infections. Patients often receive cord-blood transplants when they cannot find a suitable donor for stem-cell transplants. Finding a donor can be especially challenging for people of African, Asian, Hispanic, Middle Eastern, southern European or mixed ethnic backgrounds.
The discovery could also lead to new treatments for thrombocytopenia, a condition in which the body has too few platelets. This can be the result of immune system problems, a bone marrow disorder such as leukemia (blood cancer), some viral infections or the use of certain medications. Thrombocytopenia is a particular problem for premature babies — the more premature the baby is, the more severe the condition tends to be. Many premature babies require platelet transfusions to reduce their risk of uncontrolled bleeding inside the body.
Promisingly, there are already drugs to inhibit Dyrk1a — that could flip the biological switch in megakaryocytes. These drugs are being evaluated to battle diseases ranging from Alzheimer’s to diabetes. The availability of the drugs should speed human trials testing the clinical benefits of manipulating megakaryocytes, the researchers say. “Fortunately, these megakaryocytes can be grown in large numbers from umbilical cord blood cells,” said researcher Kamaleldin E. Elagib, MBBS, PhD, of UVA’s Department of Pathology.
Goldfarb, the associate director of UVA Health’s Clinical Hematology Laboratory, notes that the new discovery could have far-reaching benefits. “In the short term, we hope to improve the efficiency of donor-independent platelet production to the point where it could be scaled up for routine clinical use. In the long term, we hope to identify new patient treatments that could stimulate rapid platelet recovery,” he said. “Our findings offer a perfect example of how studying infantile versus adult cell development can yield clinical benefits.”
The research was supported by the National Institutes of Health, grants R01 HL130550 and R01 HL149667.