关键词： epistasis   genetic diversification   mistranslation   molecular evolution   phenotypic mutations  

摘要： Darwinian evolution preferentially follows mutational pathways whose individual steps increase fitness. Alternative pathways with mutational steps that do not increase fitness are less accessible. Here, we show that mistranslation, the erroneous incorporation of amino acids into nascent proteins, can increase the accessibility of such alternative pathways and, ultimately, of high fitness genotypes. We subject populations of the beta-lactamase TEM-1 to directed evolution in Escherichia coli under both low- and high-mistranslation rates, selecting for high activity on the antibiotic cefotaxime. Under low mistranslation rates, different evolving TEM-1 populations ascend the same high cefotaxime-resistance peak, which requires three canonical DNA mutations. In contrast, under high mistranslation rates they ascend three different high cefotaxime-resistance genotypes, which leads to higher genotypic diversity among populations. We experimentally reconstruct the adaptive DNA mutations and the potential evolutionary paths to these high cefotaxime-resistance genotypes. This reconstruction shows that some of the DNA mutations do not change fitness under low mistranslation, but cause a significant increase in fitness under high-mistranslation, which helps increase the accessibility of different high cefotaxime-resistance genotypes. In addition, these mutations form a network of pairwise epistatic interactions that leads to mutually exclusive evolutionary trajectories towards different high cefotaxime-resistance genotypes. Our observations demonstrate that protein mistranslation and the phenotypic mutations it causes can alter the evolutionary exploration of fitness landscapes and reduce the predictability of evolution.

关键词： Electromagnetic transients   Transmission line models   Phase-domain models   EMT-type programs   Frequency-dependent soil parameters  

摘要： The universal line model (ULM) is a transmission line model developed directly in the phase domain that is recognized for its accuracy and generality. It is currently the reference model for transient studies, but is exclusively found on commercial electromagnetic transients programs. This paper describes an implementation of ULM in the Alternative Transients Program (ATP), which is free for licensed users, using the foreign models tool and the type-94 component available in this platform. The implemented model is validated through comparisons with EMTP-RV. Then, it is used to investigate transients on overhead transmission lines considering a rigorous representation of the ground return impedance and ground admittance assuming frequency-dependent ground parameters.

关键词： Electric vehicles   Business model   Innovation adoption   Psychological antecedents   Psychosocial view  

摘要： Electric vehicles (EVs) are one of the major green technologies, and existing literature has extensively examined consumer adoption of EVs in an EV-buying business model. By contrast, little attention has been paid to consumers' adoption of EVs in non-ownership-based business models. To fill this literature gap, this study examines the psychological antecedents to, and influencing mechanism for, consumers to adopt EVs in different business models. Using time-lagged design, we show that need for uniqueness (NFU) trait enhances consumers' psychosocial view of EVs. This in turn promotes consumers' intention to adopt EVs in innovative business models such as EV leasing and business-to-consumer EV sharing. We further find that risk aversion negatively affects intention to adopt EVs in innovative business models only. Furthermore, consumers' intention to adopt EVs in innovative business models is positively associated with their intention to buy EVs. Moving beyond the EVbuying business model, we contribute to the sustainable innovation literature by exploring the psychological antecedents to, and mediator of, the psychosocial view in consumers' adoption of EVs in different business models. Our work has significant value for green marketing and public policies of sustainable innovations.

关键词： Virtual environment   Wayfinding   Co-presence   Decision-making   Pre-occupancy  

摘要： The effect of the social aspects on wayfinding behavior has been largely overlooked and left to designers' predictions. This research expands the understanding of wayfinding behavior in social contexts, common to real-world scenarios, proposing an experimental approach to assess and study the impact of co-presence on wayfinding decisions. Individual and paired (dyads) participants used player-controlled characters (PCs) to interact with identical T-shaped interior virtual environments inhabited by non-player-controlled characters (NPCs) in varying social scenarios. The results indicate a correlation between co-presence and wayfinding decision-making. Individual participants' favorable decisions differed from those of dyads due to social role-taking and social empowerment. The results also indicate that co-presence affected how participants viewed physical navigation aids such as signs and lighting, highlighting the importance of co-presence as a necessary backdrop for wayfinding studies. Designing with co-presence in mind would help architects anticipate wayfinding performances in their designs pre-occupancy and facilitate new design solutions.

关键词： Biodegradable polymer   Polyester   Alkylenedionic acid   1,4-Butanediol   Clear zone formation   Hydrolysis  

摘要： Poly(butylene n-alkylenedionate)s (PBADs), which are polymers that are potentially biodegradable in various environments, exhibit excellent thermal and mechanical properties similar to those of polyethylene because of their long alkyl chains. However, although it has not yet been experimentally verified, it is known that differences in the alkyl chain length affect the biodegradability of PBADs. In this study, we synthesized PBADs with alkylene diacid units, with the number of methylene chains ranging from 11 to 14. We subsequently investigated the relationship between their biodegradability via clear-zone formation and BOD-biodegradation testing and their physical properties, including their structural characteristics, using instrumental analysis. Although the monomers 1,4-butanediol (BD) and alpha,omega-dicarboxylic acids (DCA) exhibited good biochemical oxygen demand (BOD)-biodegradability, PBADs did not, indicating that PBADs with 11-14 methylene chains do not readily degrade in natural environments. (C) 2021 Elsevier Ltd. All rights reserved.

摘要： RNA N-6-methyladenosine (m(6)A) modification plays important roles in multiple aspects of RNA regulation. m(6)A is installed cotranscriptionally by the METTL3/14 complex, but its direct roles in RNA processing remain unclear. Here, we investigate the presence of m(6)A in nascent RNA of mouse embryonic stem cells. We find that around 10% of m(6)A peaks are located in alternative introns/exons, often close to 5' splice sites. m(6)A peaks significantly overlap with RBM15 RNA binding sites and the histone modification H3K36me3. Acute depletion of METTL3 disrupts inclusion of alternative introns/exons in the nascent transcriptome, particularly at 5' splice sites that are proximal to m(6)A peaks. For terminal or variable-length exons, m(6)A peaks are generally located on or immediately downstream from a 5' splice site that is suppressed in the presence of m(6)A and upstream of a 5' splice site that is promoted in the presence of m(6)A. Genes with the most immediate effects on splicing include several components of the m(6)A pathway, suggesting an autoregulatory function. Collectively, our findings demonstrate crosstalk between the m(6)A machinery and the regulation of RNA splicing.

关键词： alternative splicing   polyploid   evolution   embryogenesis   wheat   grain development  

摘要： Among polyploid species with complex genomic architecture, variations in the regulation of alternative splicing (AS) provide opportunities for transcriptional and proteomic plasticity and the potential for generating trait diversities. However, the evolution of AS and its influence on grain development in diploid grass and valuable polyploid wheat crops are poorly understood. To address this knowledge gap, we developed a pipeline for the analysis of alternatively spliced transcript isoforms, which takes the high sequence similarity among polyploid wheat subgenomes into account. Through analysis of synteny and detection of collinearity of homoeologous subgenomes, conserved and specific AS events across five wheat and grass species were identified. A global analysis of the regulation of AS in diploid grass and polyploid wheat grains revealed diversity in AS events not only between the endosperm, pericarp and embryo overdevelopment, but also between subgenomes. Analysis of AS in homoeologous triads of polyploid wheats revealed evolutionary divergence between gene-level and transcript-level regulation of embryogenesis. Evolutionary age analysis indicated that the generation of novel transcript isoforms has occurred in young genes at a more rapid rate than in ancient genes. These findings, together with the development of comprehensive AS resources for wheat and grass species, advance understanding of the evolution of regulatory features of AS during embryogenesis and grain development in wheat.

摘要： INTRODUCTION: Direct-acting antivirals (DAAs) are curative treatments for hepatitis C. However, initiation of these treatments requires adequate healthcare access. Coronavirus 2019 (COVID-19) resulted in restrictions to healthcare services in March 2020. We examined the impact of COVID-19 on the number of individuals dispensed DAAs. METHODS: This is a cross-sectional study examining the number of individuals dispensed DAAs in Ontario, Canada, from 2018 to 2020. Time-series models determined the impact of healthcare restrictions on DAA dispensations. RESULTS: Healthcare restrictions resulted in a 49.3% decrease in DAA dispensations (P = 0.026). DISCUSSION: COVID-19-related healthcare restrictions significantly affected access to DAAs. Studies exploring the long-term effects on reduced treatment are needed.

关键词： Replacement   Sacha inchi meal   Soybean meal   Growth performance   Red hybrid tilapia  

摘要： A 10-week feeding trial was conducted to examine the effect of dietary sacha inchi meal (SIM) as a soybean meal (SBM) replacer on growth performance, feed utilization, whole-body fatty acid composition, blood biochemistry, and histological changes in red hybrid tilapia, Oreochromis niloticus x O. mossambicus. Five isonitrogenous and isolipidic diets were formulated with 0 (control diet), 110, 220, 320, and 420 g/kg replacement of SBM with SIM (referred to as SIM0. 420). Each diet was randomly assigned to one of five fish groups in a 100 L indoor tank (n = 15 each, average initial weight 9.36 +/- 0.02 g) with four replicates. During the last 2 weeks of the feeding trial, 5 g/kg chromic oxide (Cr2O3) was added to the diet to determine the apparent digestibility coefficient (ADC). The results showed that SIM inclusion significantly increased growth performance, feed utilization, and ADC of dry matter in a quadratic manner with the highest final weight observed in the SIM110 group. Survival rates were not significantly affected by SIM inclusion levels (P > 0.05). The amount of n-3 fatty acids in the whole-body fish, particularly that of C18:3n-3, was linearly and quadratically increased (P < 0.001) with increasing dietary SIM inclusions. Total cholesterol and triglycerides (TGs) were linearly and quadratically decreased in the fish fed the SIM inclusion diets (P < 0.05), but no linear or quadratic effects of dietary treatments were observed on levels of total protein, albumin, globulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Liver histology showed a significant increase in cytoplasmic vacuolization with increasing SIM inclusion in diets, and fish fed the SIM420 diet showed hepatocyte swelling and displacement of hepatocyte nuclei toward the periphery. Similarly, intestine histology detected a significant linear reduction in villi height and villi thickness with increasing level of dietary SIM (P < 0.001). Overal

关键词： COVID-19   Vaccine-preventable   Traveler   Emerging infections   Re-emerging infections  

摘要： The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the phenomena of vaccine hesitancy and refusal.