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- ItemBA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection(Springer Nature, 2022-06-17) Cao, Yunlong; Yisimayi, Ayijiang; Jian, Fanchong; Song, Weiliang; Xiao, Tianhe; Wang, Lei; Du, Shuo; Wang, Jing; Li, Qianqian; Chen, Xiaosu; Yu, Yuanling; Wang, Peng; Zhang, Zhiying; Liu, Pulan; An, Ran; Hao, Xiaohua; Wang, Yao; Wang, Jing; Feng, Rui; Sun, Haiyan; Zhao, Lijuan; Zhang, Wen; Zhao, Dong; Zheng, Jiang; Yu, Lingling; Li, Can; Zhang, Na; Wang, Rui; Niu, Xiao; Yang, Sijie; Song, Xuetao; Chai, Yangyang; Hu, Ye; Shi, Yansong; Zheng, Linlin; Li, Zhiqiang; Gu, Qingqing; Shao, Fei; Huang, Weijin; Jin, Ronghua; Shen, Zhongyang; Wang, Youchun; Wang, Xiangxi; Xiao, Junyu; Xie, Xiaoliang SunneySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
- ItemThe Effect of ß-Glucan Prebiotic on Kidney Function, Uremic Toxins and Gut Microbiome in Stage 3 to 5 Chronic Kidney Disease (CKD) Predialysis Participants: A Randomized Controlled Trial(MDPI, 2022-02-14) Ebrahim, Zarina; Proost, Sebastian; Tito, Raul Yhossef; Raes, Jeroen; Glorieux, Griet; Moosa, Mohammed Rafique; Blaauw, ReneeThere is growing evidence that gut dysbiosis contributes to the progression of chronic kidney disease (CKD) owing to several mechanisms, including microbiota-derived uremic toxins, diet and immune-mediated factors. The aim of this study was to investigate the effect of a ß-glucan prebiotic on kidney function, uremic toxins and the gut microbiome in stage 3 to 5 CKD participants. Fifty-nine participants were randomized to either the ß-glucan prebiotic intervention group (n = 30) or the control group (n = 29). The primary outcomes were to assess kidney function (urea, creatinine and glomerular filtration rate), plasma levels of total and free levels of uremic toxins (p-cresyl sulfate (pCS), indoxyl-sulfate (IxS), p-cresyl glucuronide (pCG) and indoxyl 3-acetic acid (IAA) and gut microbiota using 16S rRNA sequencing at baseline, week 8 and week 14. The intervention group (age 40.6 ± 11.4 y) and the control group (age 41.3 ± 12.0 y) did not differ in age or any other socio-demographic variables at baseline. There were no significant changes in kidney function over 14 weeks. There was a significant reduction in uremic toxin levels at different time points, in free IxS at 8 weeks (p = 0.003) and 14 weeks (p < 0.001), free pCS (p = 0.006) at 14 weeks and total and free pCG (p < 0.001, p < 0.001, respectively) and at 14 weeks. There were no differences in relative abundances of genera between groups. Enterotyping revealed that the population consisted of only two of the four enterotypes: Bacteroides 2 and Prevotella. The redundancy analysis showed a few factors significantly affected the gut microbiome: these included triglyceride levels (p < 0.001), body mass index (p = 0.002), high- density lipoprotein (p < 0.001) and the prebiotic intervention (p = 0.002). The ß-glucan prebiotic significantly altered uremic toxin levels of intestinal origin and favorably affected the gut microbiome.
- ItemAdvocacy, activism, and lobbying: How variations in interpretation affects ability for academia to engage with public policy(PLOS, 2022-03-18) Jessani, Nasreen S.; Ling, Brenton; Babcock, Carly; Valmeekanathan, Akshara; Holtgrave, David R.Research and teaching are considered core-responsibilities for academic researchers. “Practice” activities however are viewed as ancillary, despite university emphasis on their importance. As funders, governments, and academia address the role of research in social impact, the deliberations on researcher activism, advocacy and lobbying have seen a resurgence. This study explores the perceptions of 52 faculty and 24 government decisionmakers on the roles, responsibilities, and restrictions of an academic to proactively engage in efforts that can be interpreted under these three terms. Data was coded through inductive thematic analysis using Atlas.Ti and a framework approach. We found that discordant perceptions about how much activism, advocacy and lobbying faculty should be engaging in, results from how each term is defined, interpreted, supported and reported by the individuals, the School of Public Health (SPH), and government agencies. Influential faculty factors included: seniority, previous experiences, position within the institution, and being embedded in a research center with an advocacy focus. Faculty views on support for advocacy were often divergent. We surmise therefore, that for effective and mutually beneficial collaboration to occur, academic institutions need to align rhetoric with reality with respect to encouraging modes and support for government engagement. Similarly, government agencies need to provide more flexible modes of engagement. This will contribute to alleviating confusion as well as tension leading to more effective engagement and consequently opportunity for evidence-informed decision making in public health globally.
- ItemAdoption Factors and Moderating Effects of Age and Gender That Influence the Intention to Use a Non-Directive Reflective Coaching Chatbot(SAGE Publications, 2022-06) Terblanche, Nicky; Kidd, MartinChatbots are increasingly applied in various contexts including helping professions, such as organizational and life coaching. Coaching facilitates individual wellness, behavioral change, and goal attainment in a reflective, non-directive manner, and is considered one of the fastest-growing professions. The use of knowledge imparting service chatbots have been studied; however, the application of chatbots in coaching has received scant research attention, raising the question about which factors and moderating effects play a role in the adoption of reflective, non-directive coaching chatbots. In this study, we applied a modified Unified Theory of the Acceptance and Use of Technology (UTAUT) model to determine factors and moderating effects of age and gender that influence the adoption of a goal-attainment coaching chatbot. Partial least squares structural equation modeling (PLS-SEM) was used for the analysis of a cross-sectional UTAUT survey (n = 226). Performance expectancy, social influence, and facilitating conditions had significant roles as direct determinants of intent to use the coaching chatbot. Gender moderated performance expectancy and age showed a moderation tendency on effort expectancy. This study on non-directive, reflective chatbots in the organizational, and life coaching domains contributes to our understanding of how to design chatbots aimed at helping people find their own answers.
- ItemEffects of damping constant of electron and size on quantum-based frequency-dependent dielectric function of small metallic plasmonic devices(Elsevier B.V, 2022-07) Akinyemi, Lateef; Oladejo, Sunday; Ekwe, Stephen; Imoize, Agbotiname Lucky; Ojo, Stephen AbiodunElectron surface dissipation and quantum-limited size tend to control the material properties of exterior plasmon oscillation as the size of metal nanoparticles goes into the nanoscale domain. The need to examine this characteristic behaviour and its potential becomes imperative. This study explores the effects of the damping constant of electrons and size quantum-based frequency-dependent dielectric function (FDDF) of small metallic materials using an elementary model of electrons in a confined box. The frequency-dependent dielectric function is employed to study quantum size impacts and damping constant in the optical spectra region. The quantum amended frequency-dependent dielectric function and the absorbing spectra of silver-cube geometry for different sizes by adding damping constant and without damping constant are critically examined. The findings reveal that when the damping constant effect is absent, the multiple crests emerge for the quantum-amended frequency-dependent dielectric function and absorbing spectra of the metallic materials, highlighting the electronic discretization levels in the tiny quantum-limited structure. While the damping constant is included, the multiple summits are hidden and vanish owing to a considerable widening of the structures independently. The change in the numerical results from the quantum case to the classical case for growing widths is further illustrated for both cases. The numerical results enhance our knowledge of damping constant dissipation and quantum limited-size impact in small-scaled plasmonic devices.