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"Campbell, Elizabeth"
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Molnupiravir: coding for catastrophe
Molnupiravir, a wide-spectrum antiviral that is currently in phase 2/3 clinical trials for the treatment of COVID-19, is proposed to inhibit viral replication by a mechanism known as ‘lethal mutagenesis’. Two recently published studies reveal the biochemical and structural bases of how molnupiravir disrupts the fidelity of SARS-CoV-2 genome replication and prevents viral propagation by fostering error accumulation in a process referred to as ‘error catastrophe’.
Journal Article
Nature, place, and story : rethinking historic sites in Canada
\"National historic sites commemorate decisive moments in the making of Canada. But when seen through an environmental lens, these sites become artifacts of the occupation and transformation of nature into a nation. In an age of pressing discussions about environmental sustainability, there is a growing need to know more about the history of our relationship with the natural world and what lessons these places of public history, regional identity, and national narrative can teach us. Nature, Place, and Story provides new interpretations for five of Canada's largest and most iconic historic sites: L'Anse aux Meadows, Newfoundland; Grand Pré, Nova Scotia; Fort William, Ontario; the Forks of the Red River, Manitoba; and the Bar U Ranch, Alberta. At each location, Claire Campbell rewrites public history as environmental history, revealing the country's debt to the power and fragility of the natural world, and the relevance of the past to understanding climate change, agricultural sustainability, wilderness protection, urban reclamation, and fossil fuel extraction. From the medieval Atlantic to modern ranch lands, environmental history speaks directly to contemporary questions about the health of Canada's habitat. Bringing together public and environmental history in an entirely new way, Nature, Place, and Story is a lively and ambitious call for a new way to view and comprehend natural heritage.\"--Site de l'éditeur.
Book
Structures and functions of coronavirus replication–transcription complexes and their relevance for SARS-CoV-2 drug design
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed millions of people and continues to cause massive global upheaval. Coronaviruses are positive-strand RNA viruses with an unusually large genome of ~30 kb. They express an RNA-dependent RNA polymerase and a cohort of other replication enzymes and supporting factors to transcribe and replicate their genomes. The proteins performing these essential processes are prime antiviral drug targets, but drug discovery is hindered by our incomplete understanding of coronavirus RNA synthesis and processing. In infected cells, the RNA-dependent RNA polymerase must coordinate with other viral and host factors to produce both viral mRNAs and new genomes. Recent research aiming to decipher and contextualize the structures, functions and interplay of the subunits of the SARS-CoV-2 replication and transcription complex proteins has burgeoned. In this Review, we discuss recent advancements in our understanding of the molecular basis and complexity of the coronavirus RNA-synthesizing machinery. Specifically, we outline the mechanisms and regulation of RNA translation, replication and transcription. We also discuss the composition of the replication and transcription complexes and their suitability as targets for antiviral therapy.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses rely on a cohort of specialized viral proteins to transcribe and replicate their RNA genomes. Recent studies have improved our understanding of coronavirus RNA translation, replication and transcription, and offer new therapeutic targets.
Journal Article
The Cambridge handbook of forensic psychology
\"Forensic psychology has developed and extended from an original, narrow focus on presenting evidence to the courts to a wider application across the whole span of civil and criminal justice, which includes dealing with suspects, offenders, victims, witnesses, defendants, litigants and justice professionals. This handbook provides an encyclopedic-style source regarding the major concerns in forensic psychology. It is an invaluable reference text for practitioners within community, special hospital, secure unit, prison, probation and law enforcement forensic settings, as well as being appropriate for trainees and students in these areas. It will also serve as a companion text for lawyers and psychiatric and law enforcement professionals who wish to be apprised of forensic psychology coverage. Each entry provides a succinct outline of the topic, describes current thinking, identifies relevant consensual or contested aspects and alternative positions. Readers are presented with key issues and directed towards specialized sources for further reference\"-- Provided by publisher.
Book
Multifunctional graphene oxide/iron oxide nanoparticles for magnetic targeted drug delivery dual magnetic resonance/fluorescence imaging and cancer sensing
Graphene Oxide (GO) has recently attracted substantial attention in biomedical field as an effective platform for biological sensing, tissue scaffolds and in vitro fluorescence imaging. However, the targeting modality and the capability of its in vivo detection have not been explored. To enhance the functionality of GO, we combine it with superparamagnetic iron oxide nanoparticles (Fe3O4 NPs) serving as a biocompatible magnetic drug delivery addends and magnetic resonance contrast agent for MRI. Synthesized GO-Fe3O4 conjugates have an average size of 260 nm and show low cytotoxicity comparable to that of GO. Fe3O4 nanoparticles provide superparamagnetic properties for magnetic targeted drug delivery allowing simple manipulation by the magnetic field and magnetic resonance imaging with high r2/r1 relaxivity ratios of ~10.7. GO-Fe3O4 retains pH-sensing capabilities of GO used in this work to detect cancer versus healthy environments in vitro and exhibits fluorescence in the visible for bioimaging. As a drug delivery platform GO-Fe3O4 shows successful fluorescence-tracked transport of hydrophobic doxorubicin non-covalently conjugated to GO with substantial loading and 2.5-fold improved efficacy. As a result, we propose GO-Fe3O4 nanoparticles as a novel multifunctional magnetic targeted platform for high efficacy drug delivery traced in vitro by GO fluorescence and in vivo via MRI capable of optical cancer detection.
Journal Article
Tiny humans, big emotions : how to navigate tantrums, meltdowns, and defiance to raise emotionally intelligent children
We're in the midst of a parenting revolution that is radically changing the way we raise our kids. Gone are the days of minimising emotions: Don't Cry. You're Fine. Don't Make a Scene. As our understanding of developing brains has increased, today's parents are looking for a new way to help their children understand their feelings and learn to process them. Emotional development experts Alyssa Blask Campbell, M.Ed. and Lauren Stauble M.S. are at the forefront of a movement to foster little ones' emotional intelligence. Their revolutionary Collaborative Emotion Processing (CEP) method has been a game changer for parents and educators, and now they are sharing it with readers in this guide. 'Tiny Humans, Big Emotions' provides the tools to tackle every sort of stressful child-rearing situation.
BOOK
Diverse and unified mechanisms of transcription initiation in bacteria
Transcription of DNA is a fundamental process in all cellular organisms. The enzyme responsible for transcription, RNA polymerase, is conserved in general architecture and catalytic function across the three domains of life. Diverse mechanisms are used among and within the different branches to regulate transcription initiation. Mechanistic studies of transcription initiation in bacteria are especially amenable because the promoter recognition and melting steps are much less complicated than in eukaryotes or archaea. Also, bacteria have critical roles in human health as pathogens and commensals, and the bacterial RNA polymerase is a proven target for antibiotics. Recent biophysical studies of RNA polymerases and their inhibition, as well as transcription initiation and transcription factors, have detailed the mechanisms of transcription initiation in phylogenetically diverse bacteria, inspiring this Review to examine unifying and diverse themes in this process.In this Review, Chen, Boyaci and Campbell examine universal pathways and diverse regulatory mechanisms in transcription initiation in evolutionarily divergent bacteria, and they discuss the mechanisms whereby antimicrobials inhibit transcription initiation and the insights those mechanisms provide into the transcription cycle.
Journal Article
Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile
Fidaxomicin (Fdx) is widely used to treat
Clostridioides difficile
(
Cdiff
) infections, but the molecular basis of its narrow-spectrum activity in the human gut microbiome remains unknown.
Cdiff
infections are a leading cause of nosocomial deaths
1
. Fidaxomicin, which inhibits RNA polymerase, targets
Cdiff
with minimal effects on gut commensals, reducing recurrence of
Cdiff
infection
2
,
3
. Here we present the cryo-electron microscopy structure of
Cdiff
RNA polymerase in complex with fidaxomicin and identify a crucial fidaxomicin-binding determinant of
Cdiff
RNA polymerase that is absent in most gut microbiota such as Proteobacteria and Bacteroidetes. By combining structural, biochemical, genetic and bioinformatic analyses, we establish that a single residue in
Cdiff
RNA polymerase is a sensitizing element for fidaxomicin narrow-spectrum activity. Our results provide a blueprint for targeted drug design against an important human pathogen.
Structural analysis of
Clostridioides difficile
RNA polymerase in complex with fidaxomicin combined with biochemical, genetic and bioinformatic analyses identifies a key residue that determines fidaxomicin sensitivity.
Journal Article