Tuesday, June 08, 2021

RUDN University chemists created anti-hantavirus drugs 5 times more efficient than existing drugs

RUDN UNIVERSITY

RUDN University chemists and their colleagues from Novosibirsk State University, Novosibirsk Institute of Organic Chemistry and The State Research Center of Virology and Biotechnology VECTOR have obtained a new class of compounds that inhibit the replication of the deadly Hantaan virus that affects blood vessels and internal organs of humans. The resulting substances were 5 times more effective than existing antiviral drugs. The results have been published Bioorganic & Medicinal Chemistry Letters.

The Hantaan virus causes acute haemorrhagic fever with renal syndrome (HFRS). The disease is common in the Asian part of Russia, China, Korea, Finland, Sweden, and the countries of eastern and central Europe. The main reservoir and carrier of the virus is the striped field mouse. A human can be infected through the skin or mucous membranes. The virus accumulates and replicates in the blood vessels causing their inflammation, affects the internal organs, primarily the kidneys. The mortality rate varies in different regions from 1% to 10-15%. There are no standard treatment regimens for HFRS -- the treatment is symptomatic. In this regard, the efforts of many scientific groups are focused on the cure development, including the synthesis of new antiviral drugs. RUDN chemists and their colleagues from Novosibirsk synthesized a new class of compounds based on the available natural substances (terpenes), which suppressed the reproduction of the virus in cells 5 times more effective than existing drugs in preliminary experiments.

"The study of antiviral drugs based on terpenes (hydrocarbons, which are found in large quantities in many plants and their essential oils), is very promising. We previously discovered a class of novel terpenoids active against the influenza virus, specifically camphor-based hydrazones. Now our goal is to find new drugs based on natural terpenes with specific activity to viruses causing HFRS", Fedor Zubkov, PhD, Associate Professor at RUDN department of Organic chemistry.

In previous studies chemists have synthesized derivatives of N-acylhydrazones of camphor and fenchone, which were active against smallpox and influenza viruses. One of these substances served as the starting point of this work. The new drug was obtained from natural camphor and fenchone. They can be extracted from the essential oils and resin of conifer trees. Using these substances, chemists obtained terpenic compounds and combined them with a heterocyclic fragment. As a result, a broad library of structurally diverse compounds was obtained - with or without a double bond, additional functional groups in the heterocyclic core, and so on. The composition of the resulting compounds was studied using 2D NMR spectroscopy.

Chemists tested the biological activity of the obtained compounds on pseudovirus system -- a biologically safe virus with the same glycoproteins on its surface as hantavirus. Such a model allows scientists to evaluate the bioactivity faster and safer than using a real virus. Chemists compared the results with the effects of broad-spectrum antiviral drugs Ribavirin and Triazavirin. 12 of the produced drugs demonstrated antiviral activity; one of them was 5 times more effective than Ribavirin and Triazavirin. Chemists concluded that the key structural feature necessary for the effective action of the drug the presence of the isoindole fragment attached to the terpene fragment.

"This class of compounds does not prevent the virus from entering the cell, but it inhibits its intracellular replication. Therefore, we can conclude that the therapeutic target of the obtained terpene complexes is the Hantaan virus protein responsible for replication", Alexandra Antonova, student at RUDN Department of Organic Chemistry.

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Research advances one step closer to stem cell therapy for type 1 diabetes

Salk research shows how to optimize the production of insulin-producing cells from stem cells

SALK INSTITUTE

Research News

IMAGE: THIS IMAGE SHOWS FUNCTIONAL BETA CELLS MADE FROM HUMAN PLURIPOTENT STEM CELLS. INSULIN (RED) AND NKX6.1 (GREEN) INDICATE TWO PROTEINS PRODUCED BY BETA CELLS. view more
CREDIT: SALK INSTITUTE

LA JOLLA--(June 7, 2021) Type 1 diabetes, which arises when the pancreas doesn't create enough insulin to control levels of glucose in the blood, is a disease that currently has no cure and is difficult for most patients to manage. Scientists at the Salk Institute are developing a promising approach for treating it: using stem cells to create insulin-producing cells (called beta cells) that could replace nonfunctional pancreatic cells.

In a study published on June 7, 2021, in the journal Nature Communications, the investigators reported that they have developed a new way to create beta cells that is much more efficient than previous methods. Additionally, when these beta cells were tested in a mouse model of type 1 diabetes, the animals' blood sugar was brought under control within about two weeks.

"Stem cells are an extremely promising approach for developing many cell therapies, including better treatments for type 1 diabetes," says Salk Professor Juan Carlos Izpisua Belmonte, the paper's senior author. "This method for manufacturing large numbers of safe and functional beta cells is an important step forward."

In the current work, the investigators started with human pluripotent stem cells (hPSCs). These cells, which can be derived from adult tissues (most often the skin), have the potential to become any kind of cell found in the adult body. Using various growth factors and chemicals, the investigators coaxed hPSCs into beta cells in a stepwise fashion that mimicked pancreatic development.

Producing beta cells from hPSCs in the lab is not new, but in the past the yields of these precious cells have been low. With existing methods, only about 10 to 40 percent of cells become beta cells. By comparison, techniques used to create nerve cells from hPSCs have yields of about 80 percent. Another issue is that if undifferentiated cells are left in the mix, they could eventually turn into another kind cell that would be unwanted.

"In order for beta cell-based treatments to eventually become a viable option for patients, it's important to make these cells easier to manufacture," says co-first author Haisong Liu, a former member of the Belmonte lab. "We need to find a way to optimize the process."

To address the problem, the researchers took a stepwise approach to create beta cells. They identified several chemicals that are important for inducing hPSCs to become more specialized cells. They ultimately identified several cocktails of chemicals that resulted in beta cell yields of up to 80 percent.

They also looked at the ways in which these cells are grown in the lab. "Normally cells are grown on a flat plate, but we allowed them to grow in three dimensions," says co-first author Ronghui Li, a postdoctoral fellow in the Belmonte lab. Growing the cells in this way creates more shared surface area between the cells and allows them to influence each other, just as they would during human development.

After the cells were created, they were transplanted into a mouse model of type 1 diabetes, The model mice had a modified immune system that would not reject transplanted human cells. "We found that within two weeks these mice had a reduction of their high blood sugar level into normal range," says co-first author Hsin-Kai Liao, a staff researcher in the Belmonte lab. "The transplanted hPSC-derived beta cells were biologically functional."

The researchers will continue to study this technique in the lab to further optimize the production of beta cells. More research is needed to assess safety issues before clinical trials can be initiated in humans. The investigators say the methods reported in this paper may also be useful for developing specialized cells to treat other diseases.

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Other authors included Chao Wang, Yang Yu, Lei Shi, and Jiameng Dan of Salk; Zheying Min of Peking University; Alberto Hayek of the University of California San Diego; and Llanos Martinez Martinez and Estrella Nuñez Delicado of Universidad Católica San Antonio de Murcia, in Spain.

This work was funded by Universidad Cato?lica San Antonio de Murcia, Primafrio, The Larry L. Hillblom Foundation, The Moxie Foundation, and Diabetes Research Connection (Project Number: 15; Institution Project Number: Liu-DRC-2019).

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

Considering the potential and pitfalls of "Dr. GPT-3" in a clinic near you

New article assesses natural language computer applications in health care

THE HASTINGS CENTER

Research News

Artificial intelligence natural language computer applications are becoming increasingly sophisticated, raising the possibility that they could assume a greater role in health care, including interacting with patients. But before these applications enter the clinic, their potential and pitfalls need thoughtful exploration, states a new article in NPJ Digital Medicine.

The authors are Diane M. Korngiebel, a Hastings Center research scholar, and Sean D. Mooney, chief research information officer at University of Washington Medicine.

"There is compelling promise and serious hype in AI applications that generate natural language" Korngiebel and Mooney write, referring to OpenAI's Generative Pre-trained Transformer 3 (GPT-3) and similar technologies. The article breaks down potential health care applications into three categories: unrealistic, realistic and feasible, and realistic but challenging.

Unrealistic Applications

Natural language AI applications will not replace doctors, nurses, and other health care personnel in conversation with patients anytime soon. "Interactions with GPT-3 that look (or sound) like interactions with a living, breathing--and empathetic or sympathetic--human being are not," the authors write. In a recent test of GTP-3 for mental health counseling, for example, the application supported a simulated patient's expressed thoughts of suicide. In addition, natural language AI applications currently reflect human biases involving gender, race, and religion.

Realistic and Feasible Applications

Natural language applications could relieve health care providers of some routine tedious tasks, such as navigating complex electronic health records. And, given that they are capable of fairly natural-sounding question and answer exchanges, the applications could improve customer service online chat support and help patients with noncritical tasks such as setting up equipment in preparation for a telehealth visit. But there must be "serious guardrails" for all health care interactions, including training the applications to eliminate "harmful, prejudicial, or inappropriate vocabulary."

Realistic but Challenging Applications

GTP-3 could be used to assist with triaging noncritical patients who come to emergency departments. However, developers of the technology and people implementing it would need to be mindful of harms. For example, natural language applications that do not "speak" a patient's language might triage that patient inappropriately. "Implementation should include another means of triaging those patients who cannot, or do not wish to, use the conversational agent, which may also be too linguistically homogenous to offer culturally mindful language use," the authors write, adding that it is important to maintain a "human in the loop." A staff member would also need to review all triage forms.

The article concludes with recommendations for making sure that natural language applications are equitable. A broad range of stakeholders should be involved from the earliest stage of development through deployment and evaluation. And there should be transparency, including in the datasets used and limitations of the applications.

"We should have cautious optimism for the potential applications of sophisticated natural language processing applications to improve patient care," the authors write. "The future is coming. Rather than fear it, we should prepare for it--and prepare to benefit humanity using these applications."

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Read the full text of the article

Researchers discover how cowpea mosaic plant virus activates immune system against cancer

Immunology researchers led by Dartmouth and Dartmouth-Hitchcock's Norris Cotton Cancer Center discover how the cowpea mosaic plant virus is recognized by and strongly stimulates the immune system to attack and often eliminate cancerous tumors

DARTMOUTH-HITCHCOCK MEDICAL CENTER

Research News

IMAGE: THOUGH IT DOES NOT INFECT MAMMALS, THE COWPEA MOSAIC PLANT VIRUS IS RECOGNIZED BY AND STRONGLY STIMULATES THE IMMUNE SYSTEM TO ATTACK AND OFTEN ELIMINATE CANCEROUS TUMORS. view more
CREDIT: UCSD

LEBANON, NH - Previous work by a team of researchers led by Steven N. Fiering, PhD, Immunology and Cancer Immunotherapy researcher at Dartmouth's and Dartmouth-Hitchcock's Norris Cotton Cancer Center and Nicole Steinmetz, PhD, Jacobs School of Engineering and Moores Cancer Center, University of California San Diego, showed that a plant virus that does not infect mammals, cowpea mosaic plant virus (CPMV), when injected into cancerous tumors, strongly stimulated the immune system to attack and often eliminate the tumor. However, very little was understood about immune recognition of plant viruses and how and why CPMV is exceptionally immuno-stimulating. In a new study, the team identifies just how CPMV is recognized by the immune system, opening the door for CPMV to be pursued as a new biological drug for treatment of cancer.

CPMV is recognized by the immune system as a pathogen--any infectious agent that can cause disease--through a family of receptors on immune cells called toll-like receptors. Toll-like receptors recognize molecules that signal the invasion of a pathogen and send a warning signal to the immune cells to mobilize to attack the pathogen. When tumors are injected with CPMV, the immune system activates and attacks the tumors by way of this pathogen pattern recognition. "The recognition of CPMV by toll-like receptors illustrates how these receptors are quite flexible and recognize many more molecular patterns than immunologists previously knew," says Fiering.

During the immune stimulation process, the immune cells release proteins that signal and activate other immune cells, known as cytokines. The team's study, "Cowpea mosaic virus stimulates antitumor immunity through recognition by multiple MYD88-dependent toll-like receptors," newly published in Biomaterials, identifies the three toll-like receptors that recognize CPMV. The paper also highlights the importance of a particular cytokine, "interferon alpha," for strong anti-tumor impact when used as an in situ vaccine to treat cancer.

In situ vaccination, in which tumors are directly treated with immune stimulating reagents, have powerful potential to improve cancer immunotherapy in a safe and inexpensive manner. "In situ vaccination has made contributions already to cancer treatment. CPMV is an excellent reagent that may soon be used to help patients in the same manner," says Fiering. "The in situ vaccination treatment of a tumor by CPMV can stimulate the immune system to also attack distant metastatic tumors that have not been treated."

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Commercial development of CPMV as a biological drug for the treatment of cancer in the form of in situ vaccination is in progress by Mosaic ImmunoEngineering Inc., a biotech company co-founded by Steinmetz and Fiering with a team of scientists and entrepreneurs. The company has licensed the rights to this technology and is actively pursuing bringing it to the clinic for the direct benefit of patients.

Phase I trials of CPMV in situ vaccination in humans are planned to start in late 2021 or early 2022.

Steven N. Fiering, PhD, is a Professor of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth, and a member of the Immunology and Cancer Immunotherapy Research Program at Dartmouth's and Dartmouth-Hitchcock's Norris Cotton Cancer Center. His research interests include developing clinically useful in situ vaccination approaches to generate therapeutic anti-tumor immunity.

About Norris Cotton Cancer Center

Norris Cotton Cancer Center, located on the campus of Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH, combines advanced cancer research at Dartmouth College's Geisel School of Medicine in Hanover, NH with the highest level of high-quality, innovative, personalized, and compassionate patient-centered cancer care at DHMC, as well as at regional, multi-disciplinary locations and partner hospitals throughout NH and VT. NCCC is one of only 51 centers nationwide to earn the National Cancer Institute's prestigious "Comprehensive Cancer Center" designation, the result of an outstanding collaboration between DHMC, New Hampshire's only academic medical center, and Dartmouth College. Now entering its fifth decade, NCCC remains committed to excellence, outreach and education, and strives to prevent and cure cancer, enhance survivorship and to promote cancer health equity through its pioneering interdisciplinary research. Each year the NCCC schedules 61,000 appointments seeing nearly 4,000 newly diagnosed patients, and currently offers its patients more than 100 active clinical trials.

About Dartmouth-Hitchcock Health

Dartmouth-Hitchcock Health (D-HH), New Hampshire's only academic health system and the state's largest private employer, serves a population of 1.9 million across northern New England. D-H provides access to more than 2,000 providers in almost every area of medicine, delivering care at its flagship hospital, Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH. DHMC was named again in 2020 as the #1 hospital in New Hampshire by U.S. News & World Report, and recognized for high performance in 9 clinical specialties and procedures. Dartmouth-Hitchcock also includes the Norris Cotton Cancer Center, one of only 51 NCI-designated Comprehensive Cancer Centers in the nation; the Children's Hospital at Dartmouth-Hitchcock, the state's only children's hospital; affiliated member hospitals in Lebanon, Keene, and New London, NH, and Windsor, VT, and Visiting Nurse and Hospice for Vermont and New Hampshire; and 24 Dartmouth-Hitchcock clinics that provide ambulatory services across New Hampshire and Vermont. The D-H system trains nearly 400 residents and fellows annually, and performs world-class research, in partnership with the Geisel School of Medicine at Dartmouth and the White River Junction VA Medical Center in White River Junction, VT.

In Oregon, new gun violence restraining orders appear to be used as intended, but could be used more proactively

AMERICAN SOCIETY OF CRIMINOLOGY

Research News

Extreme risk protection orders (ERPOs), also known as gun violence restraining orders, are civil court orders that grant temporary restrictions on purchasing and possessing firearms for individuals determined by a civil court judge to be at extreme risk of committing violence against themselves or others. A new study examined ERPO use in Oregon in the first 15 months after it was adopted. The study found that while ERPOs are commonly considered as a tool to remove guns from dangerous individuals, they should also be considered as a tool to prevent gun purchases by dangerous individuals.

The study was conducted by researchers at Michigan State University (MSU), Columbia University, the University of Michigan, and Johns Hopkins University. It appears in Criminology & Public Policy, a publication of the American Society of Criminology.

"The findings from our study can help us better understand how these laws are being used, including what types of behaviors are prompting others to file an ERPO petition," explains April Zeoli, associate professor of criminal justice at MSU, who led the study.

As of 2020, 19 states and the District of Columbia had passed laws establishing ERPOs. Due to the newness of these laws, there is little research on the circumstances under which ERPO petitions are filed and the individuals for whom they are filed. Oregon enacted its ERPO law at the start of January 2018. Under the process, a law enforcement officer or family or household member may file a petition, and a hearing is held within one judicial business day. The petitioner has the burden of proving to the civil court judge that the respondent is at high risk for injury to themselves via suicide attempt or to others.

This study examined 93 petitions for ERPO cases through March 2019; petitions were accessed through public records requests.

At least one ERPO petition was filed in 22 of Oregon's 36 counties during the study period. Most ERPO respondents were reported by petitioners to have histories of interpersonal violence (75 percent) or suicidality (73 percent), and more than half of those were reported to have threatened suicide by using a gun. More than half of ERPO respondents reportedly made both suicide threats or attempts, and threats or use of violence against others, which is higher than in other states, the authors note.

In 56 percent of ERPO petitions, the petitioner specifically referred to the respondent as having a mental illness or mental health concern, despite the fact that Oregon law does not list mental health as a factor to be considered in ERPO petitions. Petitions filed by law enforcement were more likely to report mental illness or mental health concerns than petitions filed by others.

Also, more than half of death threats, suicide threats, or suicide attempts with known timing occurred within one week of the petition being filed, the study found, suggesting that the petitions are being used in times of immediate crisis.

The study also found that 74 percent of petitioners reported that respondents had a gun at the time of the filing, and 49 percent said respondents had recently acquired or tried to acquire a deadly weapon, 96 percent of which were firearms.

In 26 percent of cases, the petitioner did not explicitly indicate that the respondent currently had a gun. Some petitioners said they filed the ERPO petition to prevent a respondent without a gun from acquiring one out of concern about the increased risk of harm that would pose. This use of ERPO may be overlooked by policymakers and other stakeholders because ERPOs are more commonly thought of as a tool to remove guns from dangerous individuals than as a tool to prevent gun purchases by dangerous individuals, the authors suggest.

Most petitions (65 percent) in Oregon were filed by law enforcement, which is lower than in other states where non-law-enforcement individuals can file ERPOs, according to the authors. Petitions filed by law enforcement were more likely to be granted than petitions filed by family or household members.

The study concluded that ERPO petitions and orders are overwhelmingly being used as intended, that is, for cases of imminent risk of harm to self or others. Yet it is possible they could be used more.

"The number of ERPO petitions in Oregon and the number of counties without a single petition in the first 15 months of the law suggest that ERPOs may be an underused tool," suggests Jennifer Paruk, a doctoral student in criminal justice at MSU, who coauthored the study. "Greater dissemination of public information about ERPOs could increase their appropriate use so high-risk individuals and their families could benefit, especially when dangerous individuals are prevented from purchasing guns."

The authors clarify that their work, in characterizing and describing information in ERPO petitions, should not be viewed as a systematic measurement of characteristics of ERPO respondents. The study, they note, was limited by their reliance on petitions completed by individuals who may or may not know respondents' full histories. In addition, sometimes language used by petitioners was imprecise, leaving the researchers to estimate meanings. Finally, the study provides a view of ERPOs in one state and so its findings should not be generalized to other states.

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The study was funded by the NIH/NICHD supported Firearm Safety among children and Teens Consortium The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funding agencies.

#BIOPHAGES

Trained viruses prove more effective at fighting antibiotic resistance

Practice boosts phage potency in evolutionary battleground with deadly bacteria

UNIVERSITY OF CALIFORNIA - SAN DIEGO

Research News

IMAGE: AFTER COMPETING IN FLASKS, DIFFERENT STRAINS OF BACTERIA ARE MOVED TO AGAR PLATES WHERE RESEARCHERS CAN EVALUATE THE "WINNER " BY COUNTING NUMBERS OF THOSE THAT SURVIVED. BACTERIA ARE IDENTIFIED WITH... view more
CREDIT: MEYER LAB, UC SAN DIEGO

The threat of antibiotic resistance rises as bacteria continue to evolve to foil even the most powerful modern drug treatments. By 2050, antibiotic resistant-bacteria threaten to claim more than 10 million lives as existing therapies prove ineffective.

Bacteriophage, or "phage," have become a new source of hope against growing antibiotic resistance. Ignored for decades by western science, phages have become the subject of increasing research attention due to their capability to infect and kill bacterial threats.

A new project led by University of California San Diego Biological Sciences graduate student Joshua Borin, a member of Associate Professor Justin Meyer's laboratory, has provided evidence that phages that undergo special evolutionary training increase their capacity to subdue bacteria. Like a boxer in training ahead of a title bout, pre-trained phages demonstrated they could delay the onset of bacterial resistance.

The study, which included contributions from researchers at the University of Haifa in Israel and the University of Texas at Austin, is published June 8 in the Proceedings of the National Academy of Sciences.

"Antibiotic resistance is inherently an evolutionary problem, so this paper describes a possible new solution as we run out of antibiotic drug options," said Borin. "Using bacterial viruses that can adapt and evolve to the host bacteria that we want them to infect and kill is an old idea that is being revived. It's the idea of the enemy of our enemy is our friend."

The idea of using phages to combat bacterial infections goes back to the days prior to World War II. But as antibiotic drugs became the leading treatment for bacterial infections, phage research for therapeutic potential was largely forgotten. That mindset has changed in recent years as deadly bacteria continue to evolve to render many modern drugs ineffective.

Borin's project was designed to train specialized phage to fight bacteria before they encounter their ultimate bacterial target. The study, conducted in laboratory flasks, demonstrated classic evolutionary and adaptational mechanisms at play. The bacteria, Meyer said, predictably moved to counter the phage attack. The difference was in preparation. Phages trained for 28 days, the study showed, were able to suppress bacteria 1,000 times more effectively and three- to eight-times longer than untrained phage.

"The trained phage had already experienced ways that the bacteria would try to dodge it," said Meyer. "It had 'learned' in a genetic sense. It had already evolved mutations to help it counteract those moves that the bacteria were taking. We are using phage's own improvement algorithm, evolution by natural selection, to regain its therapeutic potential and solve the problem of bacteria evolving resistance to yet another therapy."

The researchers are now extending their findings to research how pre-trained phages perform on bacteria important in clinical settings, such as E. coli. They are also working to evaluate how well training methods work in animal models.

UC San Diego is a leader in phage research and clinical applications. In 2018 the university's School of Medicine established the Center for Innovative Phage Applications and Therapeutics, the first dedicated phage therapy center in North America.

"We have prioritized antibiotics since they were developed and now that they are becoming less and less useful people are looking back to phage to use as therapeutics," said Meyer. "More of us are looking into actually running the experiments necessary to understand the types of procedures and processes that can improve phage therapeutics."

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The study's full author list includes: Joshua Borin, Sarit Avrani, Jeffrey Barrick, Katherine Petrie and Justin Meyer.

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Trained and untrained phages are pitted against bacteria in battleground flasks to evaluate which is more effective at killing.

CREDIT

Meyer Lab, UC San Diego

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Sensing what plants sense: Integrated framework helps scientists explain biology and predict crop performance

IOWA STATE UNIVERSITY

Research News

AMES, Iowa - Scientists have invested great time and effort into making connections between a plant's genotype, or its genetic makeup, and its phenotype, or the plant's observable traits. Understanding a plant's genome helps plant biologists predict how that plant will perform in the real world, which can be useful for breeding crop varieties that will produce high yields or resist stress.

But environmental conditions play a role as well. Plants with the same genotype will perform differently when grown in different environments. A new study led by an Iowa State University scientist uses advanced data analytics to help scientists understand how the environment interacts with genomics in corn, wheat and oats. The results could lead to more accurate and faster models that will allow plant breeders to develop crop varieties with desirable traits.

The study was published recently in the peer-reviewed academic journal Molecular Plant.

Jianming Yu, a professor of agronomy and the Pioneer Distinguished Chair in Maize Breeding, said the study sheds light on phenotypic plasticity, or the ability of crops to adapt to environmental changes. This could help plant breeders get a better understanding of how "shapable" plant species are, or how much potential they have to perform well in different environments.

"We knew that genetic performance is context dependent. It's not static; It's dependent on environmental conditions," said Xianran Li, an adjunct associate professor and the first author of the study. "Two alleles of a gene perform differently in one environment but the same in another. What is challenging is to understand the interplay between genes and the environment under the natural field conditions. The obvious obstacle is that natural environments are much more complex than controlled laboratory conditions. How can we detect the major signals plants perceive?"

The study made use of previously gathered data on the three crop species from across the globe. A group of 17 scientists from four institutions contributed to the current study, but a much larger group of scientists carried out the initial experiments that generated the data. The dataset included 282 inbred lines of corn evaluated in the United States and Puerto Rico; 288 inbred lines of wheat evaluated in Africa, India and Middle Eastern countries; and 433 inbred populations of oats evaluated in the United States and Canada. The data included environmental conditions such as temperature and availability of sunlight. The phenotypic data analyzed in the study included yields, plant height and flowering time, or the window of time during which the plant reaches the reproductive stage.

Advanced data analytics allowed the researchers to develop an environmental index, extracting the major differentiating pattern among the studied natural field conditions. With this explicit environmental dimension defined, how individual genes respond to external signals and collectively lead to the varied final performance of an organism can be systematically evaluated.

"It is like the undiscernible pulses of a plant's perception of the outside conditions now become visible on a monitor screen," said Tingting Guo, a research scientist in agronomy and co-first author of the study.

The study "presents an integrated framework that not only reveals the genetic effect dynamics along an identified environmental index but also enables accurate performance predictions and forecasting," the authors wrote in the paper.

"We are pleased to be able to design such a framework to cover two major research areas, genome-wide association studies and genomic selection (GWAS and GS)," Yu said.

The study found the integrated framework predicted flowering time and plant height accurately, while predictions for yields were more difficult. Li said that's most likely due to how many different environmental parameters, beyond just temperature and sunlight, affect yield at different growth stages. The research team will continue refining its methods to account for more environmental factors in an effort to better predict yields.

Yu and his collaborators first developed their initial data analytics in sorghum but have since expanded their research to include other major global crops. This could help plant scientists design a better plan for finding varieties to test. Yu said applying advanced data analytics to all the available genomic, phenotypic and environmental data can help breeders zero in on varieties they're interested in much faster and more efficiently.

"We believe we have the requisite amount of data to make better predictions about plant performance," Yu said. "Now, we're trying to gain knowledge and wisdom from the data to guide the real-world decision-making process."

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Funding for the research came from U.S. Department of Agriculture's National Institute of Food and Agriculture, the U.S. Department of Energy Advanced Research Projects Agency-Energy, the National Science Foundation, the ISU Raymond F. Baker Center for Plant Breeding and the ISU Plant Sciences Institute.

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Tuesday, June 08, 2021

RUDN University chemists created anti-hantavirus drugs 5 times more efficient than existing drugs

Research advances one step closer to stem cell therapy for type 1 diabetes

Considering the potential and pitfalls of "Dr. GPT-3" in a clinic near you

Researchers discover how cowpea mosaic plant virus activates immune system against cancer

In Oregon, new gun violence restraining orders appear to be used as intended, but could be used more proactively

#BIOPHAGES

Trained viruses prove more effective at fighting antibiotic resistance

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Sensing what plants sense: Integrated framework helps scientists explain biology and predict crop performance

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