scholarly journals Imaging and visualizing SARS-CoV-2 in a new era for structural biology

2021 ◽  
Vol 11 (6) ◽  
Author(s):  
Kendra E. Leigh ◽  
Yorgo Modis
Keyword(s):  
Critical Role ◽  
New Era ◽  
Biologically Relevant ◽  
Cryo Electron Microscopy ◽  
Technological Advances ◽  
New Generation ◽  
Detailed Picture ◽  
Scientific Fields ◽  
Viral Outbreak ◽  
Scientific Endeavour

The SARS-CoV-2 pandemic has had a global impact and has put scientific endeavour in the spotlight, perhaps more than any previous viral outbreak. Fortuitously, the pandemic came at a time when decades of research in multiple scientific fields could be rapidly brought to bear, and a new generation of vaccine platforms was on the cusp of clinical maturity. SARS-CoV-2 also emerged at the inflection point of a technological revolution in macromolecular imaging by cryo-electron microscopy, fuelled by a confluence of major technological advances in sample preparation, optics, detectors and image processing software, that complemented pre-existing techniques. Together, these advances enabled us to visualize SARS-CoV-2 and its components more rapidly, in greater detail, and in a wider variety of biologically relevant contexts than would have been possible even a few years earlier. The resulting ultrastructural information on SARS-CoV-2 and how it interacts with the host cell has played a critical role in the much-needed accelerated development of COVID-19 vaccines and therapeutics. Here, we review key imaging modalities used to visualize SARS-CoV-2 and present select example data, which have provided us with an exceptionally detailed picture of this virus.

scholarly journals Children of the reform and opening-up: China’s new generation and new era of development

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Chunling Li
Keyword(s):  
Critical Role ◽  
Social Changes ◽  
New Era ◽  
Education Expansion ◽  
Generational Identity ◽  
The One ◽  
The Life Course ◽  
New Generation ◽  
Reform And Opening Up ◽  
Opening Up

Abstract China’s new generation, born during the 1980s and 1990s, is a social cohort that has grown up in the era of reform and opening-up. They are simultaneously influenced by and play a critical role in a series of significant historical events in the aftermath of the reform and opening-up. The life course of this generation is intertwined with significant social changes, such as fast economic growth, the one-child policy, education expansion, the rise of the Internet, marketization, industrialization, urbanization, and globalization. These changes greatly affect their living circumstances and opportunities, shaping the generational characteristics while widening the intergenerational gap between them and the previous generations. At the same time, however, China’s new generation is unable to break the constraints of the social structure. The shared generational identity fails to eliminate the socioeconomic disparities within the generation. In contrast, marketization has strengthened the Chinese class structure through intergenerational transmission. In China’s new era of development, promoting equal opportunities and narrowing socioeconomic inequality among the new generation now proves to be a new challenge.

Family Support in Early Hearing Detection and Intervention (EHDI) Systems

2012 ◽  
Vol 22 (1) ◽  
pp. 11-21
Author(s):  
Patti Martin ◽  
Nannette Nicholson ◽  
Charia Hall
Keyword(s):  
Family Support ◽  
Hard Of Hearing ◽  
Critical Role ◽  
Annual Conference ◽  
Federal Law ◽  
Think Tank ◽  
Learning Collaborative ◽  
Technological Advances ◽  
Improved Outcomes ◽  
Program Components

Family support has evolved from a buzzword of the 1990s to a concept founded in theory, mandated by federal law, valued across disciplines, and espoused by both parents and professionals. This emphasis on family-centered practices for families of young children with disabilities, coupled with federal policy initiatives and technological advances, served as the impetus for the development of Early Hearing Detection and Intervention (EHDI) programs (Nicholson & Martin, in press). White, Forsman, Eichwald, and Muñoz (2010) provide an excellent review of the evolution of EHDI systems, which include family support as one of their 9 components. The National Center for Hearing Assessment and Management (NCHAM), the Maternal and Child Health Bureau, and the Center for Disease Control Centers cosponsored the first National EHDI Conference. This conference brought stakeholders including parents, practitioners, and researchers from diverse backgrounds together to form a learning collaborative (Forsman, 2002). Attendees represented a variety of state, national, and/or federal agencies and organizations. This forum focused effort on the development of EHDI programs infused with translating research into practices and policy. When NCHAM, recognizing the critical role of family support in the improvement of outcomes for both children and families, created a think tank to investigate the concept of a conference centered on support for families of children who are deaf or hard of hearing in 2005, the “Investing in Family Support” (IFSC) conference was born. This conference was specifically designed to facilitate and enhance EHDI efforts within the family support arena. From this venue, a model of family support was conceptualized and has served as the cornerstone of the IFSC annual conference since 2006. Designed to be a functional framework, the IFSC model delineates where and how families find support. In this article, we will promote and encourage continued efforts towards defining operational measures and program components to ultimately quantify success as it relates to improved outcomes for these children and their families. The authors view this opportunity to revisit the theoretical underpinnings of family support, the emerging research in this area, and the basics of the IFSC Model of Family Support as a call to action. We challenge professionals who work with children identified as deaf or hard of hearing to move family support from conceptualization to practices that are grounded in evidence and ever mindful of the unique and dynamic nature of individual families.

scholarly journals Application of Cryo-Electron Microscopy on Drug Discovery

2021 ◽  
Vol 27 (S1) ◽  
pp. 3250-3250
Author(s):  
Viswanath Vittaladevaram ◽  
Kranthi Kuruti
Keyword(s):  
Electron Microscopy ◽  
Protein Complexes ◽  
Lead Discovery ◽  
Biologically Relevant ◽  
Biological Targets ◽  
3 Dimensional ◽  
Drug Molecules ◽  
Cryo Electron Microscopy ◽  
Therapeutic Molecules ◽  
Novel Drug

AbstractThe key aspect for development of novel drug molecules is to perform structural determination of target molecule associated with its ligand. One such tool that provides insights towards structure of molecule is Cryo-electron microscopy which covers biological targets that are intractable. Examination of proteins can be carried out in native state, as the samples are frozen at -175 degree Celsius i.e. cryogenic temperatures. In addition to this, there were no limits for molecular and functional structures of proteins that can be imagined in 3-dimensional form. This includes ligands which unravel mechanisms that are biologically relevant. This will enable to better understand the mechanisms that are used for development of new therapeutics. Application of Cryo-electron microscopy is not limited to protein complexes and is considered as non-specific. Intervention of Cryo-EM would allow to analyse the structures and also able to dissect the interaction with therapeutic molecules. The study determines the usage of cryo-EM for providing resolutions that are acceptable for lead discovery. It also provides support for lead optimization and also for discovery of vaccines and therapeutics.

Biologically relevant arene ruthenium metalla-assemblies

CrystEngComm ◽  
2015 ◽  
Vol 17 (3) ◽  
pp. 484-491 ◽  
Author(s):  
Bruno Therrien
Keyword(s):  
Ruthenium Complexes ◽  
Building Blocks ◽  
Biological Applications ◽  
New Era ◽  
Biologically Relevant

Arene ruthenium complexes have become popular building blocks for the preparation of metalla-assemblies with biological applications, opening a new era for arene ruthenium complexes.

scholarly journals Single-particle cryo-EM—How did it get here and where will it go

Science ◽  
2018 ◽  
Vol 361 (6405) ◽  
pp. 876-880 ◽  
Author(s):  
Yifan Cheng
Keyword(s):  
Electron Microscopy ◽  
Structural Biology ◽  
Single Particle ◽  
Electron Crystallography ◽  
The Past ◽  
Cryo Electron Microscopy ◽  
Technological Advances ◽  
The Future ◽  
Electron Cryotomography

Cryo–electron microscopy, or simply cryo-EM, refers mainly to three very different yet closely related techniques: electron crystallography, single-particle cryo-EM, and electron cryotomography. In the past few years, single-particle cryo-EM in particular has triggered a revolution in structural biology and has become a newly dominant discipline. This Review examines the fascinating story of its start and evolution over the past 40-plus years, delves into how and why the recent technological advances have been so groundbreaking, and briefly considers where the technique may be headed in the future.

scholarly journals Planning and Development for a New Generation of Gas Turbine Propelled Ships in the U.S. Navy

1974 ◽  
Author(s):  
R. Goldman ◽  
R. Peterson
Keyword(s):  
World War Ii ◽  
Gas Turbine ◽  
Aircraft Engines ◽  
World War ◽  
Technological Advances ◽  
Prime Movers ◽  
Plant Characteristics ◽  
Base Of Support ◽  
New Generation ◽  
The U.S

In the early 1970s, gas turbine technology had reached the stage where it became feasible to consider marinization of state-of-the-art aircraft engines. Approximately concurrently with these technological advances, the U.S. Navy had the need to project replacements for many of its conventionally propelled surface ships of World War II vintage. Characteristics of good fuel economy coupled with potentially viable reliability and maintenance characteristics conditioned the development of main and auxiliary gas turbine prime movers for ships. Ship design, therefore, was strongly influenced by previously unavailable power plant characteristics. New ships are building and others actively being designed to draw upon these technological advantages, and a broad base of support is being established to ensure the continued long range mobility of the U.S. Navy’s ships.

scholarly journals Molecular Aspects of Varicella-Zoster Virus Latency

2018 ◽  
Author(s):  
Daniel P. Depledge ◽  
Tomohiko Sadaoka ◽  
Werner J. D. Ouwendijk
Keyword(s):  
Varicella Zoster Virus ◽  
Molecular Mechanisms ◽  
Neurological Complications ◽  
In Vitro Models ◽  
New Era ◽  
Varicella Zoster ◽  
Virus Latency ◽  
Technological Advances ◽  
Molecular Aspects

Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and the establishment of a lifelong latent infection in ganglionic neurons. VZV reactivates in about one-third of infected individuals to cause herpes zoster, often accompanied by neurological complications. The restricted host range of VZV and, until recently, the lack of suitable in vitro models to study VZV latency have seriously hampered molecular studies of viral latency. Nevertheless, recent technological advances facilitated a series of exciting studies that resulted in the discovery of a VZV latency-associated transcript (VLT) and have redefined our understanding of VZV latency and factors that initiate reactivation. Together, these findings pave the way for a new era of research that may finally unravel the precise molecular mechanisms that govern latency. In this review, we will summarize the implications of recent discoveries in the VZV latency field from both a virus and host perspective and provide a roadmap for future studies.

scholarly journals An overview of microtubule targeting agents for cancer therapy

2019 ◽  
Vol 70 (3) ◽  
pp. 160-172
Author(s):  
Bensu Karahalil ◽  
Sevgi Yardım-Akaydin ◽  
Sultan Nacak Baytas
Keyword(s):  
Cancer Therapy ◽  
Adverse Effects ◽  
Current Knowledge ◽  
Critical Role ◽  
Cancer Therapies ◽  
Therapeutic Approaches ◽  
Microtubule Targeting Agents ◽  
Traditional Drug ◽  
Preclinical And Clinical Studies ◽  
New Generation

AbstractThe entire world is looking for effective cancer therapies whose benefits would outweigh their toxicity. One way to reduce resistance to chemotherapy and its adverse effects is the so called targeted therapy, which targets specific molecules (“molecular targets”) that play a critical role in cancer growth, progression, and metastasis. One such specific target are microtubules. In this review we address the current knowledge about microtubule-targeting agents or drugs (MTAs/MTDs) used in cancer therapy from their synthesis to toxicities. Synthetic and natural MTAs exhibit antitumor activity, and preclinical and clinical studies have shown that their anticancer effectiveness is higher than that of traditional drug therapies. Furthermore, MTAs involve a lower risk of adverse effects such as neurotoxicity and haemotoxicity. Several new generation MTAs are currently being evaluated for clinical use. This review brings updated information on the benefits of MTAs, therapeutic approaches, advantages, and challenges in their research.

scholarly journals Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs

2018 ◽  
Author(s):  
David M. Kern ◽  
SeCheol Oh ◽  
Richard K. Hite ◽  
Stephen G. Brohawn
Keyword(s):  
Lipid Bilayers ◽  
Critical Role ◽  
Anion Channel ◽  
Lipid Binding ◽  
Channel Structure ◽  
Anion Channels ◽  
Cryo Electron Microscopy ◽  
Lipid Nanodiscs ◽  
Insight Into

AbstractHypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here we present single-particle cryo-electron microscopy structures of LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel.

scholarly journals Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
George Ueda ◽  
Aleksandar Antanasijevic ◽  
Jorge A Fallas ◽  
William Sheffler ◽  
Jeffrey Copps ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
De Novo ◽  
Viral Glycoprotein ◽  
Influenza Hemagglutinin ◽  
Self Assembling ◽  
Cryo Electron Microscopy ◽  
Viral Glycoproteins ◽  
Protein Nanoparticles ◽  
New Generation ◽  
Tailored Design

Multivalent presentation of viral glycoproteins can substantially increase the elicitation of antigen-specific antibodies. To enable a new generation of anti-viral vaccines, we designed self-assembling protein nanoparticles with geometries tailored to present the ectodomains of influenza, HIV, and RSV viral glycoprotein trimers. We first de novo designed trimers tailored for antigen fusion, featuring N-terminal helices positioned to match the C termini of the viral glycoproteins. Trimers that experimentally adopted their designed configurations were incorporated as components of tetrahedral, octahedral, and icosahedral nanoparticles, which were characterized by cryo-electron microscopy and assessed for their ability to present viral glycoproteins. Electron microscopy and antibody binding experiments demonstrated that the designed nanoparticles presented antigenically intact prefusion HIV-1 Env, influenza hemagglutinin, and RSV F trimers in the predicted geometries. This work demonstrates that antigen-displaying protein nanoparticles can be designed from scratch, and provides a systematic way to investigate the influence of antigen presentation geometry on the immune response to vaccination.

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