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A garden called home
\"A little girl goes to her mother's homeland and develops an appreciation for nature. Returning to Canada she plants a garden that represents both sides of her heritage as Taiwanese plants grow side-by-side with Canadian wildflowers.\"-- Provided by publisher.
Book
Authoritarian Audiences, Rhetoric, and Propaganda in International Crises
How do government rhetoric and propaganda affect mass reactions in international crises? Using two scenario-based survey experiments in China, one hypothetical and one that selectively reminds respondents of recent events, we assess how government statements and propaganda impact Chinese citizens’ approval of their government’s performance in its territorial and maritime disputes. We find evidence that citizens disapprove more of inaction after explicit threats to use force, suggesting that leaders can face public opinion costs akin to audience costs in an authoritarian setting. However, we also find evidence that citizens approve of bluster—vague and ultimately empty threats—suggesting that talking tough can provide benefits, even in the absence of tough action. In addition, narratives that invoke future success to justify present restraint increase approval, along with frames that emphasize a shared history of injustice at the hands of foreign powers.
Journal Article
Domestic Politics, China's Rise, and the Future of the Liberal International Order
With the future of liberal internationalism in question, how will China's growing power and influence reshape world politics? We argue that views of the Liberal International Order (LIO) as integrative and resilient have been too optimistic for two reasons. First, China's ability to profit from within the system has shaken the domestic consensus in the United States on preserving the existing LIO. Second, features of Chinese Communist Party rule chafe against many of the fundamental principles of the LIO, but could coexist with a return to Westphalian principles and markets that are embedded in domestic systems of control. How, then, do authoritarian states like China pick and choose how to engage with key institutions and norms within the LIO? We propose a framework that highlights two domestic variables—centrality and heterogeneity—and their implications for China's international behavior. We illustrate the framework with examples from China's approach to climate change, trade and exchange rates, Internet governance, territorial sovereignty, arms control, and humanitarian intervention. Finally, we conclude by considering what alternative versions of international order might emerge as China's influence grows.
Journal Article
Rates and drivers of aboveground carbon accumulation in global monoculture plantation forests
Restoring forest cover is a key action for mitigating climate change. Although monoculture plantations dominate existing commitments to restore forest cover, we lack a synthetic view of how carbon accumulates in these systems. Here, we assemble a global database of 4756 field-plot measurements from monoculture plantations across all forested continents. With these data, we model carbon accumulation in aboveground live tree biomass and examine the biological, environmental, and human drivers that influence this growth. Our results identify four-fold variation in carbon accumulation rates across tree genera, plant functional types, and biomes, as well as the key mediators (e.g., genus of tree, endemism of species, prior land use) of variation in these rates. Our nonlinear growth models advance our understanding of carbon accumulation in forests relative to mean annual rates, particularly during the next few decades that are critical for mitigating climate change.
Tree planting is a promising yet controversial natural climate solution. Here the authors perform a global analysis of aboveground C accumulation in tree monocultures, identifying key predictors such as prior land use, taxonomic identity, and plant traits.
Journal Article
Correlation between Phenotypic and In Silico Detection of Antimicrobial Resistance in Salmonella enterica in Canada Using Staramr
Whole genome sequencing (WGS) of Salmonella supports both molecular typing and detection of antimicrobial resistance (AMR). Here, we evaluated the correlation between phenotypic antimicrobial susceptibility testing (AST) and in silico prediction of AMR from WGS in Salmonella enterica (n = 1321) isolated from human infections in Canada. Phenotypic AMR results from broth microdilution testing were used as the gold standard. To facilitate high-throughput prediction of AMR from genome assemblies, we created a tool called Staramr, which incorporates the ResFinder and PointFinder databases and a custom gene-drug key for antibiogram prediction. Overall, there was 99% concordance between phenotypic and genotypic detection of categorical resistance for 14 antimicrobials in 1321 isolates (18,305 of 18,494 results in agreement). We observed an average sensitivity of 91.2% (range 80.5–100%), a specificity of 99.7% (98.6–100%), a positive predictive value of 95.4% (68.2–100%), and a negative predictive value of 99.1% (95.6–100%). The positive predictive value of gentamicin was 68%, due to seven isolates that carried aac(3)-IVa, which conferred MICs just below the breakpoint of resistance. Genetic mechanisms of resistance in these 1321 isolates included 64 unique acquired alleles and mutations in three chromosomal genes. In general, in silico prediction of AMR in Salmonella was reliable compared to the gold standard of broth microdilution. WGS can provide higher-resolution data on the epidemiology of resistance mechanisms and the emergence of new resistance alleles.
Journal Article
Chronic viral coinfections differentially affect the likelihood of developing long COVID
BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763).
Journal Article
Reversion mutations in phosphoprotein P of a codon-pair-deoptimized human respiratory syncytial virus confer increased transcription, immunogenicity, and genetic stability without loss of attenuation
Recoding viral genomes by introducing numerous synonymous nucleotide substitutions that create suboptimal codon pairs provides new live-attenuated vaccine candidates. Because recoding typically involves a large number of nucleotide substitutions, the risk of de-attenuation is presumed to be low. However, this has not been thoroughly studied. We previously generated human respiratory syncytial virus (RSV) in which the NS1, NS2, N, P, M and SH ORFs were codon-pair deoptimized (CPD) by 695 synonymous nucleotide changes (Min A virus). Min A exhibited a global reduction in transcription and protein synthesis, was restricted for replication
in vitro
and
in vivo
, and exhibited moderate temperature sensitivity. Here, we show that under selective pressure by serial passage at progressively increasing temperatures, Min A regained replication fitness and lost its temperature sensitivity. Whole-genome deep sequencing identified numerous missense mutations in several genes, in particular ones accumulating between codons 25 and 34 of the phosphoprotein (P), a polymerase cofactor and chaperone. When re-introduced into Min A, these P mutations restored viral transcription to wt level, resulting in increased protein expression and RNA replication. Molecular dynamic simulations suggested that these P mutations increased the flexibility of the N-terminal domain of P, which might facilitate its interaction with the nucleoprotein N, and increase the functional efficiency of the RSV transcription/replication complex. Finally, we evaluated the effect of the P mutations on Min A replication and immunogenicity in hamsters. Mutation P[F28V] paradoxically reduced Min A replication but not its immunogenicity. The further addition of one missense mutation each in M and L generated a version of Min A with increased genetic stability. Thus, this study provides further insight into the adaptability of large-scale recoded RNA viruses under selective pressure and identified an improved CPD RSV vaccine candidate.
Journal Article
Genome wide characterization of enterotoxigenic Escherichia coli serogroup O6 isolates from multiple outbreaks and sporadic infections from 1975-2016
Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea globally, particularly among children under the age of five in developing countries. ETEC O6 is the most common ETEC serogroup, yet the genome wide population structure of isolates of this serogroup is yet to be determined. In this study, we have characterized 40 ETEC O6 isolates collected between 1975-2016 by whole genome sequencing (WGS) and by phenotypic antimicrobial susceptibility testing. To determine the relatedness of isolates, we evaluated two methods-whole genome high-quality single nucleotide polymorphism (whole genome-hqSNP) and core genome SNP analyses using Lyve-SET and Parsnp respectively. All isolates were tested for antimicrobial susceptibility using a panel of 14 antibiotics. ResFinder 2.1 and a custom quinolone resistance determinants workflow were used for resistance determinant detection. VirulenceFinder 1.5 was used for prediction of the virulence genes. Thirty-seven isolates clustered into three major clades (I, II, III) by whole genome-hqSNP and core genome SNP analyses, while three isolates included in the whole genome-hqSNP analysis only did not cluster with clades I-III by both analyses and formed a distantly related outgroup, designated clade IV. Median number of pairwise whole genome-hqSNPs in clonal ETEC O6 outbreaks ranged from 0 to 5. Of the 40 isolates tested for antimicrobial susceptibility, 18 isolates were pansusceptible. Twenty-two isolates were resistant to at least one antibiotic, nine of which were multidrug resistant. Phenotypic antimicrobial resistance (AR) correlated with AR determinants in 22 isolates. Thirty-two isolates harbored both enterotoxin virulence genes while the remaining 8 isolates had only one of the two virulence genes. In summary, whole genome-hqSNP and core genome SNP analyses from this study revealed similar evolutionary relationships and an overall diversity of ETEC O6 isolates independent of time of isolation. Less than 5 pairwise hqSNPs between ETEC O6 isolates is circumstantially indicative of an outbreak cluster. Findings from this study will be a basis for quicker outbreak detection and control by efficient subtyping by WGS.
Journal Article
Reoccurring Escherichia coli O157:H7 Strain Linked to Leafy Greens–Associated Outbreaks, 2016–2019
Genomic characterization of an Escherichia coli O157:H7 strain linked to leafy greens–associated outbreaks dates its emergence to late 2015. One clade has notable accessory genomic content and a previously described mutation putatively associated with increased arsenic tolerance. This strain is a reoccurring, emerging, or persistent strain causing illness over an extended period.
Journal Article