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High-resolution cryo-EM structures of outbreak strain human norovirus shells reveal size variations
Noroviruses are a leading cause of foodborne illnesses worldwide. Although GII.4 strains have been responsible for most norovirus outbreaks, the assembled virus shell structures have been available in detail for only a single strain (GI.1). We present high-resolution (2.6- to 4.1-Å) cryoelectron microscopy (cryo-EM) structures of GII.4, GII.2, GI.7, and GI.1 human norovirus outbreak strain virus-like particles (VLPs). Although norovirus VLPs have been thought to exist in a single-sized assembly, our structures reveal polymorphism between and within genogroups, with small, medium, and large particle sizes observed. Using asymmetric reconstruction, we were able to resolve a Zn2+ metal ion adjacent to the coreceptor binding site, which affected the structural stability of the shell. Our structures serve as valuable templates for facilitating vaccine formulations.
Journal Article
The prosthodontic management of medication-related osteonecrosis of the jaw: a case report
Medication-related osteonecrosis of the jaw (MRONJ) has clear staging and management guidance from the American Association of Oral and Maxillofacial Surgeons. There is, however, less guidance on the prosthodontic rehabilitation for this cohort of patients. This paper aims to bring increased understanding on the staging of MRONJ as well as approaches to its prosthodontic management. This case report outlines a removable prosthodontic method that successfully rehabilitated a patient suffering from MRONJ. This case is well documented with the use of clinical photography. The article demonstrates techniques in overcoming the challenges of necrotic bone in the denture-bearing area, and how such methods can improve both tissue health and patient symptoms.Key pointsProvides an overview of the epidemiology of medication-related osteonecrosis of the jaw (MRONJ) and the latest staging criteria.Highlights how removable prosthodontics can potentially reduce MRONJ's progression and arrest its symptoms.Presents clear photographic documentation and description of the techniques used.
Journal Article
Introduction to the Hospitality Industry
\"Readers preparing to work in hospitality will enter a field that is quickly evolving. The rise of the global economy, ecotourism, internet commerce, and changing consumer demands are just some of the factors they will be dealing with in this exciting and dynamic industry. This new edition gives readers the foundation they need to thrive in today's hospitality industry, covering everything from finance to operational issues. The Eighth Edition of Introduction to the Hospitality Industry features both historical perspectives and discussions of new trends in a variety of sectors. This edition includes additional international examples of hospitality and tourism operations have been included throughout the text. This book covers all the latest trends, challenges, and opportunities in the hospitality industry. Readers will have a strong overview of the industry, where it fits into the broader world, the major issues and challenges in the field, and the many possible career paths that await them\"-- Provided by publisher.
Book
A shape-shifting nuclease unravels structured RNA
RNA turnover pathways ensure appropriate gene expression levels by eliminating unwanted transcripts. Dis3-like 2 (Dis3L2) is a 3′–5′ exoribonuclease that plays a critical role in human development. Dis3L2 independently degrades structured substrates, including coding and noncoding 3′ uridylated RNAs. While the basis for Dis3L2’s substrate recognition has been well characterized, the mechanism of structured RNA degradation by this family of enzymes is unknown. We characterized the discrete steps of the degradation cycle by determining cryogenic electron microscopy structures representing snapshots along the RNA turnover pathway and measuring kinetic parameters for RNA processing. We discovered a dramatic conformational change that is triggered by double-stranded RNA (dsRNA), repositioning two cold shock domains by 70 Å. This movement exposes a trihelix linker region, which acts as a wedge to separate the two RNA strands. Furthermore, we show that the trihelix linker is critical for dsRNA, but not single-stranded RNA, degradation. These findings reveal the conformational plasticity of Dis3L2 and detail a mechanism of structured RNA degradation.
The authors employ cryogenic electron microscopy and kinetic analysis to characterize the discrete steps of how the Dis3L2 3′–5′ exoribonuclease recognizes and degrades structured RNA targets.
Journal Article
Introduction to Management in the Hospitality Industry
\"Readers seeking management careers in hospitality will enter a dynamic industry filled with opportunities. The rewards are many, but so are the challenges. Today's hospitality managers must deal with such complex factors as globalization, terrorism threats, ecotourism, internet commerce, new business and financial models, and rapidly changing consumer demands. Introduction to Management in the Hospitality Industry, 10th Edition gives readers the industry know-how and the management skills needed to thrive in all aspects of the field, from food service to lodging to tourism. The Tenth Edition of Introduction to Management in the Hospitality Industry features both historical perspectives and discussions of new trends in a variety of sectors. This book has the most thorough coverage of the hospitality industry, covering foodservice, lodging, and travel and tourism, hospitality careers, and hospitality management. Upon successful completion of this text, readers will have a strong grasp of the many facets of the hospitality industry\"-- Provided by publisher.
Book
Pain Reduction With an Immersive Digital Therapeutic Tool in Women Living With Endometriosis-Related Pelvic Pain: Randomized Controlled Trial
Chronic pelvic pain is a common and disabling condition in women living with endometriosis. Pharmacological and surgical treatments are not always effective at controlling pain and present important restrictions. Digital therapeutics (DTx) are emerging as major nonpharmacological alternatives that aim to extend the analgesic therapeutic arsenal of patients.
In this randomized controlled trial (RCT), we aimed to measure the immediate and 4-hour persisting effects of a single use 20-minute DTx (Endocare) on pain in women experiencing pelvic pain due to endometriosis.
A total of 45 women with endometriosis participated in a randomized controlled study comparing the analgesic effect of a single use of a virtual reality digital treatment named Endocare (n=23, 51%) to a 2D digital control (n=22, 49%). Perceived pain and pain relief were measured before the treatment and 15, 30, 45, 60, and 240 minutes after the end of the treatment.
The clustered posttreatment pain was significantly reduced compared to the pretreatment for both Endocare and the control group (all P<.01). Endocare was significantly more effective than the control group (all P<.01). Endocare decreased the mean pain intensity from 6.0 (SD 1.31) before the treatment to 4.5 (SD 1.71) posttreatment, while the control only decreased it from 5.7 (SD 1.36) to 5.0 (SD 1.43). When comparing each posttreatment measures to the pretest, Endocare significantly reduced pain perception for all points in time up to 4 hours posttreatment. The differences did not reached significance for the control group. Moreover, Endocare was significantly superior to the control group 15, 30, and 45 minutes after the treatment (all P<.001). The mean perceived pain relief was significantly higher for Endocare at 28% (SD 2%) compared to the control, which was 15% (SD 1%) for all the posttreatment measurements (all P>.05).
Our study aimed to test the effects of a single use of a DTx treatment on reported pain at different time points in women diagnosed with endometriosis experiencing moderate-to-severe pelvic pain. Importantly, our results support that Endocare, a virtual reality immersive treatment, significantly reduce pain perception compared to a digital control in women living with endometriosis. Interestingly, we are the first to notice that the effect persisted up to 4 hours posttreatment.
ClinicalTrials.gov NCT04650516; https://tinyurl.com/2a2eu9wv.
Journal Article
All that is silver is not toxic: silver ion and particle kinetics reveals the role of silver ion aging and dosimetry on the toxicity of silver nanoparticles
Background
When suspended in cell culture medium, nano-objects composed of soluble metals such as silver can dissolve resulting in ion formation, altered particle properties (e.g. mass, morphology, etc.), and modulated cellular dose. Cultured cells are exposed not just to nanoparticles but to a complex, dynamic mixture of altered nanoparticles, unbound ions, and ion-ligand complexes. Here, three different cell types (RAW 264.7 macrophages and bone marrow derived macrophages from wild-type C57BL/6 J mice and Scavenger Receptor A deficient (SR-A
(−/−)
) mice) were exposed to 20 and 110 nm silver nanoparticles, and RAW 264.7 cells were exposed to freshly mixed silver ions, aged silver ions (ions incubated in cell culture medium), and ions formed from nanoparticle dissolution. The In Vitro Sedimentation, Diffusion, Dissolution, and Dosimetry Model (ISD3) was used to predict dose metrics for each exposure scenario.
Results
Silver nanoparticles, freshly mixed ions, and ions from nanoparticle dissolution were toxic, while aged ions were not toxic. Macrophages from SR-A
(−/−)
mice did not take up 20 nm silver nanoparticles as well as wild-types but demonstrated no differences in silver levels after exposure to 110 nm nanoparticles. Dose response modeling with ISD3 predicted dose metrics suggest that amount of ions in cells and area under the curve (AUC) of ion amount in cells are the most predictive of cell viability after nanoparticle and combined nanoparticle/dissolution-formed-ions exposures, respectively.
Conclusions
Results of this study suggest that the unbound silver cation is the ultimate toxicant, and ions formed extracellularly drive toxicity after exposure to nanoparticles. Applying computational modeling (ISD3) to better understand dose metrics for soluble nanoparticles allows for better interpretation of in vitro hazard assessments.
Journal Article