Inaugural Article Research Articles

Four decades of Eukaryotic DNA replication: From yeast genetics to high-resolution cryo-EM structures of the replisome

I had my eyes set on DNA replication research when I took my first molecular biology course in graduate school. My election to the National Academy of Sciences came just when I was retiring from active research. It gives me an opportunity to reflect on my personal journey in eukaryotic DNA replication research, which started as a thought experiment and culminated in witnessing the determination of the cryoelectron microscopic structure of the yeast replisome in the act of transferring histone-encoded epigenetic information at the replication fork. I would like to dedicate this inaugural article to my talented trainees and valuable collaborators in gratitude for the joy they gave me in this journey. I also want to thank my mentors who instilled in me the purpose of science. I hope junior scientists will not be disheartened by the marathon nature of research, but mindful enough to integrate and pause for other equally fun and meaningful activities of life into the marathon.

Qualitative Comparative Policy Studies: An Introduction from the Special Section Editors

This inaugural article delineates the vision and scope of the new section “Qualitative Comparative Policy Studies” of the Journal of Comparative Policy Analysis. The co-editors present the five key features of the section: the comparative, the transnational, the relational, the global, and the self-reflective. Concretely, they invite contributions on qualitative empirical research that (i) is comparative in its methods and interpretive framework, (ii) draws on the transnational dimension, (iii) considers the relational dimension of network governance, (iv) recognizes an unequal global setting, and (v) is self-reflective and interrogates international comparison as a governance tool. By definition, qualitative comparison is contextual comparison that differentiates between place and space and the temporalities of comparative policy analysis (period, timing, tempo, sequence, lifespan, and age).

@theSource: Welcome.

This inaugural article sets the stage and scope for a new department in IEEE Computer Graphics and Applications: @theSource. In this department, we set out to address the questions, "How have open source projects and open Standards driven graphics innovations and applications?" and "What can we learn from them?" Thus, we are broadly concerned with how open communities and ecosystems have (and are) impacting computer graphics. The intent is to highlight: open source software (such as architectures, engines, frameworks, libraries, services); open Standards and open source data and models; and applications as well as the impacts of open graphics technologies. We also consider historical and summative reviews on the cultural and economic aspects of open source and open Standards graphics ecosystems, such as visualization and mixed reality.

Contribution of microscopy to a better understanding of the anatomy of pathogenic protists

In this Inaugural Article the author briefly revises its scientific career and how he starts to work with parasitic protozoa. Emphasis is given to his contribution to topics such as a) the structural organization of the surface of protozoa using freeze-fracture and deep-etching; b) the cytoskeleton of protozoa, especially structures such as the subpellicular microtubules of trypanosomatids, the conoid of Toxoplasma gondii, microtubules and inner membrane complex of this protozoan, and the costa of Tritrichomonas foetus; c) the flagellulm of trypanosomatids, that in addition to the axoneme contains a complex network of filaments that constitute the paraflagellar rod; d) special organelles such as the acidocalcisome, hydrogenosome, and glycosome; and e) the highly polarized endocytic pathway found in epimastigote forms of Trypanosoma cruzi.

Social psychological research on gender, sexuality, and relationships: reflections on contemporary scientific and cultural challenges

This inaugural article considers two types of challenges – scientific and cultural – facing researchers who study gender, sexualities, and relationships. For the scientific challenges, I focus on the tension between constructing parsimonious theories while simultaneously accounting for the complexity of gender, sexuality, and relationships. I focus on ambivalent sexism theory as an example that illustrates both the advantages and disadvantages of parsimonious theories before turning to a topic for which achieving parsimony has been elusive: gender identity. Finally, I address the current, highly politicized cultural environment, addressing attempts to suppress gender and sexual diversity, as well as to silence teaching and research on these topics.

Grand challenges in organizational justice, diversity and equity

This inaugural article founding the Frontiers Journal Section on Organizational Justice, Diversity and Equity highlights four broad areas requiring further research in our field. First, organizational justice and DEI share common threads, and there is considerable room for work that conceptually integrates these two areas of study. Specifically, we need research that helps us understand how organizations as inequality-producing systems create and maintain perceptions of (un)fairness when individuals receive unequal rewards for their contributions, particularly in diverse workplaces. Furthermore, research is needed to enhance understanding of how to create and maintain high levels of organizational justice for both marginalized and predominant identity groups. Additionally, this is a space for empirical work that replicates prior findings, something that is essential to the development of science. It is also important to expand the scope of justice and DEI scholarship with a greater inclusion of research contexts from the Global South. Finally, Organizational Justice and DEI topics are inflamed in the contemporary U.S. context, and there is a need for investigation of how the societal context influences the development of our field.

Co-infection of mud crab Reovirus (MCRV) and Staphylococcus saprophyticus in giant mud crab, Scylla serrata (Forsskal, 1775)

The culture of animals in a controlled environment can be a factor in disease transmission. Mud Crab Reovirus (MCRV) and staphylococcus saprophyticus were co-infected in Scylla serrata, in a fattening pen from MGR Thittu, Cuddalore District, Tamil Nadu, Southeast coast of India. Lethargic, sluggish, partially atrophied hepatopancreas, loose gills, and discoloration of the animal characterized the spontaneously infected moribund crab. Viral invasion in the hepatopancreas with basophilic inclusion was evaluated in the histopathological studies. Molecular evidence shows reovirus infection in crab. Scanning electron microscopy reveals the presence of cocci bacteria. The 16 s RNA sequencing and phylogenetic analysis confirm the infected bacteria were Staphylococcus saprophyticus. Ultrastructural studies provided evidence for the coinfection of MCRV and Staphylococcus saprophyticus. This is the inaugural article on the co-infection of reovirus and bacteria in the mud crab Scylla serrata.

Quantum-Chemical Approach to Nuclear Magnetic Resonance of Paramagnetic Systems

Nuclear magnetic resonance (NMR) is a central method for investigating the microscopic structure and dynamics of molecules and materials, with numerous applications in science, technology, and medicine. Computational modelling is indispensable in NMR research due to the indirect nature of NMR information and the rich physical phenomenology behind its observables. While NMR is conventionally used to study diamagnetic systems, paramagnetic NMR (pNMR) of electronically open-shell systems is rapidly gaining importance. This inaugural article concerns the methodology and application of computational molecular science to the observables pNMR, including current challenges and outlook for the future.

Editor's Choice Articles for December.

Editor's Choice Articles for December.

Parametric or nonparametric statistical tests: Considerations when choosing the most appropriate option for your data.

This article serves as the second in a series that offers recommendations for optimal data reporting, specifically focusing on statistical methods most frequently reported by the Cytopathology audience. The inaugural article, Recommendations for reporting statistical results when comparing proportions, dealt with the most common category of reported statistical tests over 2.5 years of Cytopathology articles-comparing proportions. Comparing samples using t tests, Mann-Whitney U, analysis of variance, and Kruskal-Wallis tests was another common category of statistical test reported among this audience. An important distinction between these tests is based on whether the samples follow a normal distribution. Therefore, Parametric or nonparametric statistical tests: Choosing the most appropriate option for your data is the second topic in the series. While this article will review considerations when selecting parametric or nonparametric statistical tests, an extensive review of each method is beyond the scope of this summary. The author encourages the reader to consult with a trained statistician to map out a thorough analytical plan (including their recommendations for the appropriate statistical test[s] to use) prior to data collection.

Profile of Ginés Morata

Gines Morata grew up in remote village in southeast Spain. As a child, he says, he had no scientific role models or sources of inspiration. Yet, by the end of graduate school, Morata had made two groundbreaking discoveries in Drosophila that are still influencing the field of developmental biology, including the discoveries of developmental compartments and the phenomenon of cell competition. His Inaugural Article examines how mutant cells in Drosophila outsmart cell competition to form tumors (1). For his accomplishments, Morata has received multiple awards, including Spain’s Prince of Asturias Prize for Science and Technology and foreign membership in the Royal Society in London. A research professor at the Spanish National Research Council and the Autonomous University of Madrid, Morata was elected as an international member of the US National Academy of Sciences in 2018. Morata grew up in a modest household in Rioja, Almeria, Spain. His father was a traffic cop, and his mother stayed home with their four sons and a daughter. Although neither parent had any formal education, both emphasized the importance of school, says the second-born Morata. The family did not have money for secondary school, let alone college, but Morata’s good grades earned him scholarships that sent him first to the nearby city of Almeria for secondary school and, later, to the Complutense University in Madrid for college. Gines Morata. Image credit: Jose A. Perez (Centro de Biologia Molecular, Madrid, Spain). Although Morata loved watching birds and snakes as a child, he did not feel any affinity for biology at that age. When he went off to Madrid for college, he thought he might study mathematics or physics, inspired by a particularly adept mathematics teacher. However, a chance discovery helped change his course. “I read a book by Linus Pauling, where he made the point …

Profile of Jennifer Marshall Graves

“Sometimes when you ask a functional question, you get an evolutionary answer,” says Jennifer Marshall Graves, a leader in the field of epigenetics and comparative genomics. Her team’s vast body of research on Australian fauna has helped the distinguished professor at Melbourne’s La Trobe University (LTU) uncover fundamental insights into mammalian sex chromosomes and sex-determining genes. Elected as an International Member of the National Academy of Sciences in 2019, Graves compared DNA sequences across widely divergent animals and demonstrates in her Inaugural Article (1) that bird and reptile microchromosomes, once thought to be insignificant, are ancient and highly conserved and represent the original building blocks of vertebrate genomes. Graves was born in Adelaide, Australia. Her father, the soil physicist T. J. Marshall, formulated the Marshall equation, which describes the movement of fluids in soil. Her mother, Ann Marshall, was a geologist and urban geographer whose activism concerning overdevelopment in Adelaide left a mark on the city. Graves recalls being “turned onto genetics” when high school biology teacher Doreen McCarthy used colorful images of budgerigars to demonstrate Mendel’s laws of genetics. Graves says, “I was hooked and enrolled in science at Adelaide University in 1960.” Shortly thereafter, during her mother’s sabbatical, she spent a semester at the University of California, Berkeley, where she studied cell biology taught by Daniel Mazia. Returning to Adelaide, she received the Sir Ronald A. Fisher Award for Genetics in 1962 and conducted honors research on X chromosome inactivation in kangaroo females with advisor David Hayman. At Adelaide, she earned both an undergraduate degree in genetics and physical chemistry and a Master’s degree in genetics. Jennifer Marshall Graves. Image credit: GAMMA/Micheline Pelletier. The Fisher Award, a £10 book token, was followed by a Fulbright Travel Grant, which enabled doctoral studies at Berkeley under Mazia and cell geneticist …

Remembering James March

On September 27, 2018, Professor James G. March, a giant in our field, passed away at the age of 90 (1928–2018), just one month after his wife and high school sweetheart, Jayne, passed away. March's impact on the field of organization studies and beyond is profound and long-lasting. The advancement of the field is truly indebted to March's brilliance and dedication to the search of truth as a great scholar. March wrote the inaugural article for Management and Organization Review (MOR) (2005), ‘Parochialism in the Evolution of a Research Community: The Case of Organization Studies’. This article not only provided a critical foundation underlying the editorial structure and philosophy of MOR but also argued eloquently for the salience of indigenous Chinese management studies as a necessary condition for building both contextualized and universal knowledge.

Profile of John R. Speakman

John Speakman’s interest in science was spurred by his early interest in birds. “I was a very keen birdwatcher, and I used to spend lots of time watching birds in my youth,” he says. At age 16, he would go to the same site every day to count small wading birds and try to work out the factors influencing their numbers. John R. Speakman. Image credit: Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. When he was deciding which university to attend, Speakman scoured university prospectuses, looking for researchers who studied wading birds and ended up choosing the University of Stirling in Scotland, where he was able to work on waders for his undergraduate project. He decided to stay at the university for his doctorate and continued studying wading birds with the same supervisor, David Bryant. “He gave me lots of guidance but also let me pursue my own thing, and I really enjoyed doing that,” says Speakman. “That basically cemented the idea that a career in science was the way for me to go,” he says. During a long and fruitful scientific career, Speakman has studied fundamental questions about energy balance. Much of his work has focused on understanding the factors governing variations in food intake and energy expenditure across a wide range of species, and he is a leading expert in the use of isotopes to measure energy expenditure and metabolism. Speakman’s research has contributed greatly to researchers’ understanding of how energy balance can influence obesity and aging. Speakman is currently a professor at the Chinese Academy of Sciences in Shenzhen, China and at the University of Aberdeen in Scotland. In his Inaugural Article, Speakman used data from mouse studies to investigate the mechanisms underlying caloric restriction, an approach to slow down aging by restricting caloric intake …

Profile of Patrick Cramer

Patrick Cramer’s interest in the scientific method may have been sparked by a childhood gift. While growing up, his parents gave him a kit to try little experiments at home that inspired him to become a scientist. Patrick Cramer. Image credit: Patrick Cramer. Cramer studied chemistry, first at the University of Stuttgart and later at Heidelberg University in Germany. “I was in love with the beauty of biological molecules, so I moved into biochemistry and then into structural biology,” says Cramer. This move was facilitated by stints at the University of Bristol and Cambridge University. “At Cambridge I really fell in love with structural biology, and so I chose that as a subject for my PhD studies at the European Molecular Biology Laboratory,” he says. At the European Molecular Biology Laboratory in Grenoble, France, Cramer began to study gene transcription, launching a career unraveling the mysteries of this fundamental biological process. Cramer has determined the three-dimensional (3D) structure of transcription complexes, providing numerous insights into the mechanisms of transcription initiation, elongation, and regulation. He has also contributed to the development of functional genomics and computational biology to study how the genome is transcribed and regulated in living cells and understand how gene activity is controlled. Now director at the Max Planck Institute for Biophysical Chemistry in Gottingen, Germany, Cramer was elected to the National Academy of Sciences in 2020. In his Inaugural Article (1), his team describes the first structures of the highly conserved transcription factor TATA-box binding protein (TBP) in complex with a nucleosome. When Cramer received his doctorate in 1998, a major question about transcription was the structure of RNA polymerase II, the central enzyme that makes messenger RNA. To work on this problem, he joined Roger Kornberg’s laboratory at Stanford University as a postdoctoral researcher, funded by …

Profile of Claude Desplan

“I have been in science for four decades and my enthusiasm is still as fresh as on the first day,” says Claude Desplan, the New York University (NYU) biology and neural science Silver professor, who in 2018 was elected as a member of the National Academy of Sciences. Focusing on Drosophila , among other model organisms, Desplan and his team have made significant contributions to the fields of molecular biology, genetics, developmental neurobiology, and electrophysiology. They have provided insights on body axis formation, the generation of neural diversity, the molecular mechanisms involved in retinal and optic lobe development, and the neural circuits underlying motion detection. Using evolutionary developmental biology, or “evo-devo,” approaches, they have elucidated how sensory systems in various organisms adapt to different ecological conditions. Desplan’s Inaugural Article (1) reviews his laboratory’s work on Drosophila over the past decade and describes neural development principles predicted to apply to most organisms, including mammals. Claude Desplan. Image credit: Danielle Desplan (photographer). Born in Algeria in 1953, Desplan was raised with an appreciation of multiple cultures. His mother's family settled in Algeria in the 19th century. Desplan says his mother, age 91, is one of the world’s oldest yoga instructors. Desplan’s father worked in law, as did many of his relatives, yet Desplan forged his own career path. He says, “I wanted to be a surgeon, but there was no good rationale for it.” When Desplan was 9 years old his family moved to France. There, he drew inspiration from his ninth-grade science teacher, whom he knew as Ms. Joschau. Desplan says, “Even though she was teaching geology at the time, I became interested in the natural sciences and decided to pursue a career in research.” At age 15 he met another woman who influenced his life. “I met Danielle,” says Desplan, …

Profile of Scott Edwards

Looking through Scott Edwards’ curriculum vitae is like wandering the halls of the natural history collections he curates: an invitation to dive deeply into one area combined with permission to think broadly and zip enthusiastically from one exhibit to another. Zoologist and curator of ornithology of Harvard’s Museum of Comparative Zoology, Edwards was elected to the National Academy of Sciences in 2015. Although Edwards primarily uses birds as models to study molecular evolution and biodiversity, he took a foray into amphibians in his Inaugural Article (1), analyzing the diminutive genome of the ornate burrowing frog. In the past, he has documented rapid genomic shifts in green anole lizards in response to winter storms in the southern United States and examined the genome sizes of organisms, ranging from bacteriophages to dinosaurs (2⇓–4). Scott Edwards on his 76-day, 3,848-mile trek across the United States during the summer of 2020. Image credit: Scott Edwards. Orioles (Icterus) in the ornithology collections of the Museum of Comparative Zoology at Harvard University. Image credit: Museum of Comparative Zoology at Harvard University/Jeremiah Trimble. As a youth, Edwards became interested in birds when a neighbor in Riverdale, New York, invited him to go birdwatching in their Bronx neighborhood. Something about matching the species in the field with pictures in a book appealed to him. When he entered Harvard University in 1981, Edwards was not thinking about studying ornithology but was instead headed toward medical school. “My dad was a doctor,” he says. “It just seemed like, ‘Well, that’s what biologists do.’” While still an undergraduate, he took a year off to learn the kinds of work that field biologists do. Edwards volunteered in collections at the Smithsonian Institution in Washington, DC, and participated in field work in Hawaii, where he was born and had …

Profile of Howard Y. Chang

Since the 1930s, when RNA was recognized as chemically distinct from DNA, scientists have known of the diversity of RNA molecules. What they could not have fathomed at the time, however, is the variety of roles, both informational and structural, that RNA plays in biology: from protein expression and regulation to chromatin remodeling and epigenetic modification. Over the past two decades, physician-scientist Howard Y. Chang has helped enrich the RNA canon. He has discovered long sequences of RNA that do not code for proteins but instead modulate DNA accessibility. He has also helped develop next-generation sequencing methods that leverage his knowledge of the interactions between DNA, RNA, and proteins. In his Inaugural Article (1), Chang, who was elected to the National Academies of Sciences in 2020 and is a professor of dermatology and of genetics at Stanford University, describes the development of BABEL, a system that uses advanced computational techniques to translate between sets of sequencing data, down to single-cell resolution. The work provides further insights into the mechanisms of DNA regulation and protein expression and may aid the development of therapeutics for diseases such as cancer. Howard Y. Chang in his laboratory at Stanford. Image credit: Howard Hughes Medical Institute. Chang was born in Taipei, Taiwan, but he, his mother, and younger brother moved to southern California when Chang was 12 years old. His father, a physician, remained in Asia. “My parents felt we would have better educational opportunities in the [United States],” Chang says. America was a major cultural shift for his family, and Chang took English classes to quickly get up to speed. He said that “The social interactions in the [United States], especially with teachers, is very different than in Taiwan.” He credits his public high school experience with laying the foundation for a successful career. …

Profile of Judy Lieberman

“I am just hitting my stride,” says immunologist Judy Lieberman, while discussing her multiple research projects. The former high-energy theoretical physicist is now a chairperson of cellular and molecular medicine at Boston Children’s Hospital and a professor of pediatrics at Harvard Medical School. Elected to the National Academy of Sciences (NAS) in 2020, Lieberman is a pioneer in the therapeutic uses of RNA interference. She showed in an animal disease model that small RNAs can be used as a therapy and developed methods for delivering small RNAs selectively to particular cell types. Her achievements also include elucidating the molecular basis of killer lymphocyte cytotoxicity and identifying the role of microRNAs in development and cancer. Her Inaugural Article (1) reports a strategy for cancer immunotherapy that uses cancer cell-targeted gene knockdown to counteract the many ways tumor cells evade immune recognition. Judy Lieberman. Image credit: Judy Lieberman. Lieberman was born in Boston and raised in the New York City area. Her father was a businessman, while her mother was an elementary school teacher. She says, “I grew up in a very intellectual family, but not of scientists, although my uncle was a professor of biochemistry and member of the NAS. My parents were early feminists, who strongly believed that girls could do anything that boys could do.” The 1957 launch of Sputnik 1, the first artificial Earth satellite, heightened interest in science and led to expansion of youth educational programs. Lieberman benefited from this surge of interest while in high school, participating in a sciences and arts summer camp supported by the Ford Foundation, a Saturday science honors program at Columbia University, and a National Science Foundation (NSF) program in modern physics at Cornell University. “The NSF program turned me onto physics,” she says. After earning a bachelor’s degree summa cum …

Profile of James H. Hurley

James “Jim” Hurley’s first introduction to crystal structures occurred when he was just 8 years old. While living north of Boulder, Colorado, his mother would take him to look for minerals near old mines in the mountains. “I learned the seven crystal systems at that age as part of learning how to identify the minerals that I found, and that came in handy later on when I did X-ray crystallography of proteins,” he says. James H. Hurley. Image credit: Calin Hurley (photographer). Hurley’s early fascination with minerals led him to a tentative interest in geology, but in college he decided to study physics instead. “As an undergraduate, I fell in love with the elegance of physics, and I was also fascinated by the complexity of life,” says Hurley. To combine those interests, Hurley pursued a doctorate in biophysics. “I thought there must be some way you could put the elegance and predictive power of physics at work to explain the incredible diversity and beauty of life, and that’s how I ended up in biophysics,” he says. Now a professor of molecular and cell biology at the University of California, Berkeley, Hurley was elected to the National Academy of Sciences in 2020. During his career, he has used precision tools, such as cryoelectron microscopy (cryo-EM), X-ray crystallography, and mass spectrometry to study the structure of proteins and membranes and the interplay between them. His work has answered fundamental questions about how these interactions influence the shape of cells and organelles and how pathogens can coopt these interactions to infect cells. In his Inaugural Article, Hurley describes the structure of an immune evasion protein of SARS-CoV-2, the virus responsible for the COVID-19 pandemic (1). After his undergraduate physics degree, Hurley studied high-energy physics at Fermilab, where he worked on a muon …