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Presentations by young Chinese aquaculture scientists: From the 2021 China Society of FisheriesAnnual Conference of Youth Scholars – World Aquaculture…

Photo by iStock 1 INTRODUCTION

Young scientists are the most active force driving scientific advancement and technological innovation. Nonetheless, young scholars also face challenges such as heavy workloads, shortage of research-focused hours, high competition in grant application, and securing an academic job, among others. Mentorship from supervisors and senior peers is important to encourage and reassure the scientific endeavors of young scholars. Favorable policies and activities arranged by public agencies or academic societies are also essential for nurturing and promoting the successful establishment of young scholars. Chinese young scientists have been making great contributions to aquaculture research and applications. The China Society of Fisheries organized the Annual Conference of Youth Scholars in Shanghai on October 18, 2021. There were over 300 attendees to this meeting, which covered the topics of aquaculture techniques and equipment, biotechnologies and breeding, nutrition and feeds, diseases and quality security, aquaculture resources and conservation, and aquaculture economy and management. Here, we summarize some representative work by the attendees who were selected for this special issue, which partially reflects the recent research focus on young aquaculture scientists in China.

The healthy and sustainable development of aquaculture depends heavily on research on nutritional feeds in terms of precise nutritional requirements of aquatic animals. The largemouth bass,Micropterus salmoides, characterized by its fast growth and delicious taste, is currently a major species of freshwater aquaculture in China. According to the China Fishery Statistical Yearbook report, the total production of farmed largemouth bass in 2020 was more than 619,500 tons, and the national demand for this fish is also increasing yearly (China Fishery Yearbook,2021). To date, the requirement of each vitamin of the largemouth bass has its own specific and irreplaceable function, so it is necessary to investigate the optimal level of usage one by one. The requirement for fat-soluble vitamins, including vitamins A, D, E, and K, has been reported in this species (Li et al.,2018,2020; Lian et al.,2017; Wei et al.,2021). In contrast, minimal information has been published on the nutritional requirements of water-soluble vitamins, particularly the B vitamins. Folic acid, one of the water-soluble B vitamins, which plays a role in maintaining normal hematopoiesis, facilitating growth performance and immune response of aquatic animals, is essential for growth maintenance in aquatic animals (Shiau & Huang,2001). Hang et al. (2022) evaluated the graded dietary levels of folic acid on growth performance, body composition, blood biochemistry, nutritional metabolism, and antioxidant immunity of largemouth bass. They found that the growth performance, total hepatic antioxidant capacity, protein content, hemoglobin, hematocrit of whole blood cells, and plasma total protein in each folic acid supplementation group were higher than those in the control group to various degrees. Dietary supplementation with 0.51.5mg/kg of folic acid significantly decreased albumin, plasma glutamic-pyruvic transaminase activity, serum malonaldehyde activity, and liver glycogen content. According to the regression analysis of growth performance and additive gradients, the optimal amount of folic acid in the feed of juvenile largemouth bass was 1.421.46mg/kg diet.

Gibel carp,Carassius auratus gibelio, is one of the main farmed carp species in China, with a total annual production of more than 2.59 million tons (Liu et al.,2018). Given the deterioration of the aquatic aquaculture environment and degradation of germplasm resources, diseases caused by bacteria and viruses have caused large-scale mortalities of farmed gibel carp and led to enormous losses (Xu et al.,2013). Among the pathogens, Cyprinid herpesvirus 2 (CyHV-2) andAeromonasspp. are the most common pathogens of carps (Sahoo et al.,2016). Thus, the use of functional feed additives that can boost the innate immune system and natural mucosal barrier of fish has attracted more attention during antibiotic-free farming. Recently, poly--hydroxybutyrate (PHB), as a polymer storing intracellular energy and carbon sources, has been gradually shown to have positive effects on growth, immunity, and disease resistance in aquatic animals (Duan et al.,2017). However, the efficacy and application method of PHB on gibel carp culture is still unclear. Liu et al. (2022) detected that dietary PHB supplementation could promote growth performance, upregulate the expression of immune-related genes and activities of immune-related enzymes, significantly enhance the disease resistance of fish, and strengthen the tight junction of the intestine and affect the intestinal mucosal barrier of gibel carps. These findings provide a good model to illustrate its immune-stimulatory mechanism in fish. It has played a guiding role in the sustainable culture of gibel carp, and may contribute to the green, environmental, and healthy development of the aquaculture industry.

Phytoplankton are the primary producers in the aquatic food web and play essential roles in the biotic water environment (Zhao et al.,2022). Most phytoplankton are single-celled photosynthetic organisms that can achieve a rapid increase in number after continuous cell cycles by cell proliferation and division in suitable environments (Dewitte & Murray,2003). Therefore, understanding the cell cycle and regulation mechanism to achieve the appropriate biomass is essential for maintaining aquatic ecosystem health. Zhao et al. (2022) summarized the current information about the eukaryotic phytoplankton cell cycle and the environmental factors that affect it. They also introduced the research methods for the phytoplankton cell cycle, highlighted the progress in understanding the molecular mechanisms of phytoplankton cell cycle regulation, and discussed future directions for phytoplankton cell cycle research. This information will strengthen our understanding of the phytoplankton cell cycle and its regulation mechanisms, inspiring further studies on maintaining aquatic and health of natural ecosystems.

There are abundant germplasm resources of freshwater pearl mussels in China.Hyriopsis cumingiiis one of the main bivalve species used for freshwater pearl culture. It is well-known that the color of pearl production is an essential criterion for evaluating the quality of pearls and further determining their market value (Li et al.,2014). Furthermore, exogenous dietary carotenoids are considered the main factor affecting the color of the inner shell and pearl (Sun et al.,2020). Therefore, studying key enzyme genes involved in carotenoid metabolism is the vital premise of pearl quality control research. Zhang et al. (2022) successfully cloned the completeHcStAR-likegene and proposed thatHcStAR-likeplays a crucial role in the accumulation of carotenoids of shell or pearl pigmentation inH. cumingiiby dsRNA interference assay. Their findings contribute to our further understanding of the shell formation mechanism of pearl color.

Dissolved oxygen is the most important limiting factor in rearing of fish and directly affects fish health and survival. How fish adapt to hypoxia in aquaculture has been a hot topic. Fish in high-latitude regions suffer from sustained hypoxia in winter and diel-cycling hypoxia in summer.Phoxinus lagowskii, a high-latitude fish distributed and mainly cultured in northeast China, was chosen to determine the biochemical, physiological, and histological responses to these two conditions (Yao et al.,2022). Histological analysis revealed changes in the relative thickness of the layers in the midbrain under hypoxia.P. lagowskiiadapts to sustained hypoxia through myocardial hypertrophy and mitochondria deformation. During diel-cycling hypoxia, the oxidative stress biomarkers, enzyme activities, and triglycerides in the heart were significantly elevated. HIF expression patterns indicated its function in diel-cycling hypoxia in the heart and sustained hypoxia in the brain. Collectively, these findings reveal thatP. lagowskiiexhibits varied adaptation strategies to the exposure of sustained and diel-cycling hypoxia.

Diseases have become one of the main constraints to sustainable aquaculture production and trade. Disease resistance is another most important trait for healthy aquaculture development in addition to stress resistance. Therefore, it is essential to uncover appropriate drugs for these diseases.

Singapore grouper iridovirus (SGIV-Gx) causes high mortality rates in mariculture, and effective treatments against SGIV-Gx infection are urgently required. Metformin is a famous drug for many diseases. ZUniet al. (2022) evaluated the therapeutic effect of metformin on SGIV-Gx. Results showed that metformin exerts a dose-dependent antiviral effect by disrupting SGIV-Gx particles, suggesting its great potential in dealing with SGIV-Gx infection. Li et al. (2022) assessed the in vivo antiviral effect ofGlycyrrhiza uralensiscomponents against SGIV infection. Results showed that the ingredients did not have significant effects against SGIV infection, whereas aqueous extract (GUF) showed significant anti-SGIV infection activity in a concentration-dependent manner, and it also destroyed the structure of virus particles, which is similar to the function of metformin.

In addition to medication, sets of gene responses to bacterial infection produce various effective proteins important for disease prevention mechanisms. Caspase genes are candidate genes because of their role in regulating apoptosis during development and inflammation. In Japanese pufferfish, 10 caspase genes were identified through bioinformatics analyses and detected in all examined tissues. The expression of 10 caspases significantly varied in a time-dependent manner afterVibrio harveyiinfection, suggesting their roles in the antibacterial process of Japanese pufferfish (Yang et al.,2022).

It was reported that many young scientists chose a science career because of their love of the work (Pain,2014). The China Society of Fisheries sponsors the Young Scientist Award and organizes the Annual Conference of Youth Scholars to promote the talents of young aquaculture researchers. Young scientists engaged in aquaculture studies, both applicable and theoretical, may enjoy both the love and productive reward from such work, because of the increasing need for technologies from the ever-expanding aquaculture industry. The Journal of the World Aquaculture Society welcomes high-quality submissions from young scholars from China or elsewhere in the world.

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For the Record, Aug. 12, 2022 | UDaily – UDaily

For the Record provides information about recent professional activities and honors of University of Delaware faculty, staff, students and alumni.

Recent presentations, publications and honors include the following:

Sharon Pitt, vice president of Information Technologies and CIO, spoke on Flexible Work in Higher Ed What Does Your Workforce Look Like? at the Higher Education CIO Congress in Washington, D.C., on Aug. 7, 2022.

Trevor A. Dawes, vice provost for libraries and museums and May Morris University Librarian, was an invited panelist for a webinar sponsored by the National Information Standards Organization (NISO) entitled, Eliminating Outdated Workflows: Developing the New, on Aug. 10, 2022. Panelists discussed how traditional workflows were suddenly subject to examination due to the COVID-19 pandemic and which workflows, whether due to the pandemic or not, have now become the standard in their respective organizations.

Ethan Joella, adjunct faculty member in the Associate in Arts Program and best-selling author of the novel A Little Hope, was the keynote speaker at theWilmington Writers' Workshop, held virtually Aug. 6, 2022. He also led a writing workshop.

Wendy Smith,Emma Smith Morris Professor of Management,andKyle Emich,associate professor of management,both in the Alfred Lerner College of Business and Economics, collaborated with colleagues onConceiving opposites together: Cultivating paradoxical frames and epistemic motivation fosters team creativity, published in the July 2022 issue ofOrganization Behavior and Human Decision Processes. A related article, Paradox Mindset: The Source of Remarkable Creativity in Teams,was covered by INSEADs Knowledge Blog. Emichhas also coauthored a paper recently published online by theJournal of Business Research. The article, A house divided: A multilevel bibliometric review of the job search literature, focuses on how economists focus on organizational budgets when considering job search, while psychologists focus on job-seeker well being.

Timothy J. Shaffer, Stavros Niarchos Foundation (SNF) Chair of Civil Discourse and faculty member in theJoseph R. Biden, Jr. School of Public Policy and Administrationand Department of Communication, is co-editor of Grassroots Engagement and Social Justice through CooperativeExtension.This book, released Aug. 1, 2022, focuses on contemporary efforts to address systemic inequities and highlights Cooperative Extension'srole in, and responsibility for, culturally relevant community education that isrooted in democratic practices and social justice. Shaffer's co-editor, Nia Imani Fields, is a 2006 Biden School alumna and serves as the Maryland 4-H program leader and assistantdirector of Maryland Extension.

Melissa Melby, professor of anthropology, coauthored the editorial Seeking shelter against contagion: households of resilience, recently published by the Canadian Science Policy Centre in its 2022 Editorial Series titled Building Resilience During International Crisis. CSPC publishes opinion, commentary and critique from members of the science and innovation community on a wide range of issues.

Zvi Schwartz, professor of hospitality business management, andTim Webb, assistant professor of hospitality business management, both in the Alfred Lerner College of Business and Economics, were awarded the Journal of Hospitality and Tourism Researchs Article of the Year Highly Commended award at the 2022 International Council of Restaurant Institutional Education Conference in Washington, D.C., for their articleResource Similarity, Market Commonality, and Spatial Distribution of Hotel Competitive SetPic

Roxanne Evande, graduate student in the Department of Medical and Molecular Sciences, has been selected as one out of 10 students nationally for the role of advocacy trainee delegate by the American Society for Biochemistry and Molecular Biology. Evandes application highlighted how this opportunity fits in with her program and current career goals, as well as her background in policy and science, such as serving on the Graduate Student Government Executive Board. The role provides a three-month externship with opportunities to learn the basics of policy and how science can be applied to it for meaningful connections between these fields, which play critical roles in how society acts against rising issues such as the COVID-19 pandemic. Evandes project aims to reexamine and improve the review process for the National Science Foundation graduate fellowships. In her research at UD, she studies the cellular mechanisms of the human papillomavirus E2 protein for effective drug development in the future.

Alisa Moldavanova, incoming associate professor and director of the Master of Public Administration program in theJoseph R. Biden, Jr. School of Public Policy and Administration, was recently elected to serve on the Association for Research on Nonprofit Organizations and Voluntary Action (ARNOVA)Board of Directors. She has been an active leader and contributor to the ARNOVA community since 2012 and is a known champion of diversity, equity and inclusion in the nonprofit research field.

Kevin Solomon, an assistant professor of chemical and biomolecular engineering, has earned the Society for Industrial Microbiology and Biotechnology (SIMB) annual Early Career Award (formerly the Young Investigator Award) for 2022. The award aims to encourage young investigators to continue their research and to recognize and support their efforts at the beginning of their career and is given to a scientist or engineer who has demonstrated outstanding scientific contributions in the field of biotechnology and or industrial microbiology. Solomon was honored at the SIMB annual meeting on Aug. 9, 2022.

Eleftherios Terry Papoutsakis, the Unidel Eugene Du Pont Chair at the Department of Chemical and Biomolecular Engineering, has earned the Society for Industrial Microbiology and Biotechnology (SIMB) annual Charles Thom Award, the societys senior award. Named after a pioneer in industrial microbiology and mycology, the award honors researchers demonstrating exceptional merit in industrial microbiology and biotechnology through research contributions and publications, and for their independence of thought and originality that added appreciably to scientific knowledge. Papoutsakis was honored at the SIMB annual meeting on Aug. 9, 2022.

This summer,Paul Laux, professor of finance and JP Morgan Chase Senior Fellow at the Lerner College, oversaw the University of Delaware/ISCTE-Lisbon University Institute Trading and Bloomberg Program. It was a two-week program for graduate students studying finance at ISCTE. As part of the program, 30 students and faculty from ISCTE participated, training in Lerners Geltzeiler Trading Center and visiting other local sites and social gatherings. Lerner Dean Bruce Weber taught a class to participants.

To submit information for inclusion in For the Record, write to ocm@udel.edu and include For the Record in the subject line.

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ThreeSixty Journalism summer camps aim to increase diversity within media – MinnPost

Isaac Santino-Garcia and Jaydin Fairbanks are frequent camp goers. In the summers, they attend the various media camps ThreeSixty Journalism hosts, like the podcast camp and its news reporter academy.

This year, they were at the television broadcast camp, where they worked on creating a broadcast news story. Santino-Garcia and Fairbanks dove into the topic of Native American boarding schools with their video.

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Topics like this need to be covered more, Santino-Garcia, an incoming junior at Cretin Derham Hall High School, said. And the best way to tell stories about different communities is to have those communities involved and lead the process.

Newsroom employees are more likely to be more white and male than U.S. workers overall, and more than three-quarters (77%) of newsroom employees are white, according to the Pew Research Center. ThreeSixty Journalism has been around for more than 20 years, partnering with the University of St. Thomas with a mission is to change how newsrooms look and the resulting narratives.

Santino-Garcia, who is Lower Sioux Dakota and White Earth Ojibwe, and half Mexican, thinks ThreeSixty puts underrepresented and marginalized voices first.

Every story Ive seen or at least heard about (in the program) has been somebody whos not Caucasian and a story that might not have been regularly told, he said.

For program graduate Samantha HoangLong, being surrounded by so many kids of color was uplifting.

It was like the first space to be a space that young with a class full of people who are also young journalists of color, she said. I feel really lucky that I was in a class full of diversity at that young age.

Part of bringing diversity into newsrooms is creating incentive, said Chad Caruthers, executive director of the journalism program. ThreeSixty also helps by giving stipends to the participants for their time and work.

It was the only reason (I attended) at first, but then I kept doing other things (camps), and I stayed because I always liked it, said Fairbanks, who is going to be a senior at Osseo High School.

The stipend allows people of various socioeconomic backgrounds to participate without the financial strain of losing income for a couple of weeks.

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As students get older in high school, they work more, they need to support their families, they need to support themselves, whatever it may be. To come to a program thats a week-long or two weeks long at St. Thomas during the summer means that they dont work over that period of time, Caruthers said. If its not extra money in their pocket, we hope that it is replacing any income that they would lose by joining us.

Because of the program, some kids are considering studying journalism or some form of media. Santino-Garcia wants to attend St. Thomas, where ThreeSixty offers a four-year scholarship.

I like learning new things, and journalism gives me a good life experience that you may not learn other places, Santino-Garcia said. It just fascinates me because I can go out and tell other peoples stories that may not have been told.

Samantha HoangLong

I actually wanted to be a dentist before that. I was like applying to college with biology and biochemistry, and I was ready to go to dental school. And then I did this camp, she said. I learned that you can talk to people for a living and learn about what they do. I thought that was really cool, so I kind of just stuck with it.

After graduating high school, she interned for ThreeSixty Journalism and learned more about video production. She received a four-year scholarship from ThreeSixty to study communication and journalism at St. Thomas.

At the most recent camp, Babs Santos from Fox 9 and Jeff Wagner from WCCO taught the students how to speak on air and how to structure a story. Another component of the program, HongLong said, was touring a newsroom.

HongLong appreciated seeing what happens behind the scenes in a newsroom.

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I think having that experience right after high school gave me an advanced look of what it could be if I worked in that job, she said. Being able to access and walk through the newsrooms was really cool. Thats what made me want to go into broadcast TV.

She went on to intern at Fox 9, then worked there after graduating college. Shes now on the audience team at Sahan Journal.

ThreeSixty does some recruiting for potential participants but also partners with various schools that identify students who would be a good fit for the program. It offers seasonal journalism workshops throughout the year and a camp per week during the summer.

Caruthers said that free and reduced lunch eligible students pay nothing for the program, but theres flexibility for other income levels. Typically, the organization aims for 80% of its participants to be free and reduced lunch qualified.

But the pandemic reduced that figure to between 50 and 75%.

Harder to reach students became, in many cases, harder to reach during the pandemic, Caruthers said. You look at all the gaps that many of us hear about in terms of education gaps, health disparities, things like that. Technology gaps are a big one, and thats part of it. When everything went to virtual, we had to do the same, and unfortunately, not all of our students have equal access to the technology that was required.

Of the total participants, roughly 10 percent pay to attend, Caruthers said. Its able to do so because of partnerships with the Center for Prevention at Blue Cross Blue Shield, which funds the projects, and helps with the topics.Blue Cross Blue Shield is a sponsor of the Race and Health Equity fellowship at MinnPost, but has no editorial say in content.

People whove attended ThreeSixty have gone on to work in newsrooms across the state. Some alumni are now at the Star Tribune, Fox 9, Sahan Journal, and MPR, among other places, Caruthers said.

MinnPost's in-depth, independent news is free for all to access no paywall or subscriptions. Will you help us keep it this way by supporting our nonprofit newsroom with a tax-deductible donation today?

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Overcoming the Impossible With DNA to Building Superconductor That Could Transform Technology – SciTechDaily

In DNA, scientists find a solution to building a superconductor that could transform technology.

Scientists have used DNA to overcome a nearly insurmountable obstacle to engineering materials that will revolutionize electronics. Published in the journal Science on July 28, the work was performed by researchers at the University of Virginia School of Medicine and their collaborators.

One possible outcome of these engineered materials could be superconductors, which have zero electrical resistance, allowing electrons to flow unimpeded. That means that, unlike current means of electrical transmission, they dont lose energy and dont create heat. Development of a superconductor that could be used widely at normal pressures and room temperature instead of at extremely high or low temperatures, as is now possible could lead to many technological wonders. These include hyper-fast computers, shrinking the size of electronic devices, allowing high-speed trains to float on magnets and slash energy use, and many more.

One such superconductor was first proposed by Stanford physicist William A. Little more than 50 years ago. Scientists have spent decades trying to make it work. However, even after validating the feasibility of his idea, they were left with a challenge that appeared impossible to overcome. Until now.

Edward H. Egelman, PhD, of the University of Virginia School of Medicines Department of Biochemistry and Molecular Genetics, has been a leader in the field of cryo-electron microscopy (cryo-EM), and he and his colleagues used cryo-EM imaging for this seemingly impossible project. It demonstrates, he said, that the cryo-EM technique has great potential in materials research. Credit: Dan Addison, UVA Communications

Edward H. Egelman, PhD, of UVAs Department of Biochemistry and Molecular Genetics, has been a leader in the field of cryo-electron microscopy (cryo-EM), and he and Leticia Beltran, a graduate student in his lab, used cryo-EM imaging for this seemingly impossible project. It demonstrates, he said, that the cryo-EM technique has great potential in materials research.

One possible way to realize Littles idea for a superconductor is to modify lattices of carbon nanotubes. These are hollow cylinders of carbon so tiny they must be measured in nanometers billionths of a meter. However, there was a huge challenge: controlling chemical reactions along the nanotubes so that the lattice could be assembled as precisely as needed and function as intended.

Egelman and his colleagues found an answer in the very building blocks of life. They took DNA, the genetic material that tells living cells how to operate, and used it to guide a chemical reaction that would overcome the great barrier to Littles superconductor. In short, they used chemistry to perform astonishingly precise structural engineering construction at the level of individual molecules. The result was a lattice of carbon nanotubes assembled specifically as needed for Littles room-temperature superconductor.

This work demonstrates that ordered carbon nanotube modification can be achieved by taking advantage of DNA-sequence control over the spacing between adjacent reaction sites, Egelman said.

For now, the lattice they built has not been tested for superconductivity. However, it offers proof of principle and has great potential for the future, the researchers say. While cryo-EM has emerged as the main technique in biology for determining the atomic structures of protein assemblies, it has had much less impact thus far in materials science, said Egelman, whose prior work led to his induction in the National Academy of Sciences, one of the highest honors a scientist can receive.

Egelman and his collaborators say their DNA-guided approach to lattice construction could have a wide variety of useful research applications, especially in physics. But it also validates the possibility of building Littles room-temperature superconductor. The scientists work, combined with other breakthroughs in superconductors in recent years, could ultimately transform technology as we know it and lead to a much more Star Trek future.

While we often think of biology using tools and techniques from physics, our work shows that the approaches being developed in biology can actually be applied to problems in physics and engineering, Egelman said. This is what is so exciting about science: not being able to predict where our work will lead.

The researchers have published their findings in the journal Science. The team consisted of Zhiwei Lin, Leticia Beltran, Zeus A. De los Santos, Yinong Li, Tehseen Adel, Jeffrey A Fagan, Angela Hight Walker, Egelman and Ming Zheng.

Reference: DNA-guided lattice remodeling of carbon nanotubes by Zhiwei Lin, Leticia C. Beltran, Zeus A. De los Santos, Yinong Li, Tehseen Adel, Jeffrey A Fagan, Angela R. Hight Walker, Edward H. Egelman and Ming Zheng, 28 July 2022, Science.DOI: 10.1126/science.abo4628

The work was supported by the Department of Commerces National Institute of Standards and Technology and by National Institutes of Health grant GM122510, as well as by an NRC postdoctoral fellowship.

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An easier and safer way to synthesize medicines – The Ohio State University News

Despite being some of the most versatile building blocks in organic chemistry, compounds called carbenes can be too hot to handle. In the lab, chemists often avoid using these highly reactive molecules due to how explosive they can be. Yet in a new study, published today in the journal Science, researchers from The Ohio State University report on a new, safer method to turn these short-lived, high-energy molecules from much more stable ones.

Carbenes have an incredible amount of energy in them, said David Nagib, co-author of the study and a professor of chemistry and biochemistry at Ohio State. The value of that is they can do chemistry that you just cannot do any other way.

In fact, members of the Nagib Lab specialize in harnessing reagents with such high chemical energy, and have helped invent a multitude of new substances and techniques that would otherwise be chemically unobtainable.

In this study, the researchers developed catalysts made out of cheap, Earth-abundant metals, like iron, copper and cobalt, and combined them to facilitate their new method of harnessing carbene.

They were able to successfully use this new strategy to channel the power of reactive carbenes to fabricate valuable molecules on a larger scale and much more quickly than traditional methods. Nagib compared this leap to engineers figuring out how to use steel to build skyscrapers rather than brick and mortar.

For instance, one molecular feature that chemists have been hard-pressed to create is cyclopropane, a small, strained ring of twisted chemical bonds found in some medicines. More recently, cyclopropane has been used as a key ingredient in the oral antiviral pill called Paxlovid. Used to treat COVID-19, the pill reduces the severity of the disease by stopping the virus from replicating, rather than killing it outright.

Although the cyclopropane needed to fabricate the drug has been difficult to create in large quantities, Nagib said he believes his labs new method could be applied to create the drug more quickly and at a larger scale. Our new method will enable better access to dozens of types of cyclopropanes for incorporation into all kinds of medicines to treat disease, he said.

While the teams research does have potential applications outside the pharmaceutical realm, like agrochemicals, Nagib said hes most passionate about how their tool could speed up the discovery of new, targeted medicines. You could technically apply our methods to anything, he said. But in our lab, we're more interested in accessing new types of more potent drugs.

Nagib predicts that, using the process his team developed, a chemical reagent that currently takes 10 or 12 steps to make (by explosive intermediates) could be done in four or five, knocking off nearly 75% of the time it takes to fabricate.

Overall, Nagib said he hopes this research will help other chemists do their work.

There are lots of really great scientists around the world who do this kind of chemistry and using our tool they could potentially have a safer lab, Nagib said. The flavor of science that we do, the most satisfying reward is when other people use our chemical methods to make important molecules better.

Other co-authors were Lumin Zhang, a former postdoctoral fellow, as well as Bethany M. DeMuynck, Alyson N. Paneque and Joy E. Rutherford, all graduate students in the department of chemistry and biochemistry and members of the Nagib Lab. The research was supported by the National Institutes of Health, the National Science Foundation and the Sloan Foundation.

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Enzyme, proteins work together to tidy up tail ends of DNA in dividing cells – University of Wisconsin-Madison

Researchers at the University of WisconsinMadison have described the way an enzyme and proteins interact to maintain the protective caps, called telomeres, at the end of chromosomes, a new insight into how a human cell preserves the integrity of its DNA through repeated cell division.

DNA replication is essential for perpetuating life as we know it, but many of the complexities of the process how myriad biomolecules get where they need to go and interact over a series of intricately orchestrated steps remain mysterious.

From left, Qixiang He, Ci Ji Lim, Xiuhua Lin.

The mechanisms behind how this enzyme, called Pol-primase, works have been elusive for decades, says Ci Ji Lim, an assistant professor of biochemistry and principal investigator on new research into DNA replication published recently in Nature. Our study provides a big breakthrough in understanding DNA synthesis at the ends of chromosomes, and it generates new hypotheses about how Pol-primase a central cog in the DNA replication machine operates.

Every time a cell divides, the telomeres at the end of the long DNA molecule that makes up a single chromosome shorten slightly. Telomeres protect chromosomes like an aglet protects the end of a shoelace. Eventually, the telomeres are so short that vital genetic code on a chromosome is exposed and the cell, unable to function normally, enters a zombie state. Part of a cells routine maintenance includes preventing excessive shortening by replenishing this DNA using Pol-primase.

At the telomere construction site, Pol-primase first builds a short nucleic acid primer (called RNA) and then extends this primer with DNA (then called RNA-DNA primer). Scientists thought Pol-primase would need to alter its shape when it switches from RNA to DNA molecule synthesis. Lims lab found that Pol-primase makes the RNA-DNA primer at telomeres using a rigid scaffold with the help of another cog in the telomere replication machine, an accessory protein called CST. CST acts like a stop-and-go sign that halts the activity of other enzymes and brings Pol-primase to the construction site.

Before this study, we had to imagine how Pol-primase works to complete telomere replication at the ends of chromosomes, says Lim. Now, we have high-resolution structures of Pol-primase bound to an accessory protein complex called CST. We found that after CST binds to the template DNA strand at the telomere, it facilitates the action of Pol-primase. In doing so, CST sets the stage for Pol-primase to first synthesize RNA and then DNA using a unified architectural platform.

The researchers also got a glimpse into how Pol-primase might initiate DNA synthesis elsewhere along the length of a chromosome. Other scientists have also found the CSTpol--primase complex at sites where DNA damage is being repaired and where DNA replication has stalled.

Because Pol-primase plays a central and very important role in DNA replication in telomeres and elsewhere along chromosomes its the only enzyme that makes primers on DNA templates from scratch for DNA replication our CSTPol-primase structure provides new insights into how Pol-primase can also do its job during genomic DNA replication, Lim says. Its a very elegant solution that nature has evolved to accomplish this complicated process.

Our findings reveal an unprecedented role that CST plays in facilitating this Pol-primase activity, explains first author Qixiang He, a graduate student in the UWMadison biophysics graduate program. It will be interesting to see if accessory factors involved in DNA replication elsewhere on chromosomes set up Pol-primase the same way as CST does for telomeres.

The researchers built the structural model of CSTPol-primase using an advanced imaging technique called cryo-electron microscopy single-particle analysis. In cryo-EM, rapidly frozen samples are suspended in a thin film of ice, then imaged with a transmission electron microscope, resulting high-resolution, 3D models of biomolecules like the enzymes at work in DNA replication.

Lims team used cryo-EM single particle analysis to first determine the structure of CSTPol-primase and then home in on visualizing moving parts of the complex in greater detail. They collected data at the UWMadison Cryo-Electron Microscopy Research Center (CEMRC), housed in the UWMadison Department of Biochemistry, and the NCI-funded National Cryo-Electron Microscopy Facility at the Frederick National Laboratory for Cancer Research.

We started with a conundrum from our biochemical assay, but once we imaged the CSTpol--primase co-complex and saw its cryo-EM structures, everything immediately became clear. This was extremely satisfying for everyone on the team. Beyond that, the structures also provide ideas that we can now design experiments to test, says Xiuhua Lin, lab manager and co-author of the new study.

Among these ideas are capturing how CSTpol-/primase works in more detail. The researchers also want to map the entire human telomere replication process, and theyre studying how CSTpol-/primase terminates its activity once the DNA at telomeres is copied.

You cant really study how a car moves by looking at its individual parts you have to assemble the parts and observe how they work together. But biomolecular machinery often has so many moving parts that it can be difficult to study, Lim says. Thats where the power and versatility of cryo-electron microscopy single-particle analysis come in. This approach allowed us to put together a high-resolution atomic model and provided critical insights into how it moves, which in turn facilitated our understanding of how the human CSTPol-primase works.

The research was supported by a grant from the National Institutes of Health (R00GM131023).

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Enzyme, proteins work together to tidy up tail ends of DNA in dividing cells - University of Wisconsin-Madison

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