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Non-volatile magnetic random-access memories (MRAMs), such as spin-transfer torque MRAM and next-generation spin-orbit torque MRAM, are emerging as key to enabling low-power technologies, which are expected to spread over large markets from embedded memories to the Internet of Things. Concurrently, the development and performances of devices based on two-dimensional van der Waals heterostructures bring ultracompact multilayer compounds with unprecedented material-engineering capabilities. Here we provide an overview of the current developments and challenges in regard to MRAM, and then outline the opportunities that can arise by incorporating two-dimensional material technologies. We highlight the fundamental properties of atomically smooth interfaces, the reduced material intermixing, the crystal symmetries and the proximity effects as the key drivers for possible disruptive improvements for MRAM at advanced technology nodes.
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As conspiracy theories around COVID-19 pose a big global challenge to public health and well-being, this study seeks to identify how and when people are likely to activate conspiratorial thinking and believe in conspiracy theories about the coronavirus. Based on a U.S. national two-wave survey (W1: N = 1,119; W2: N = 543), this study found partial support for direct effects of uncertainty on conspiratorial thinking and support for indirect effects through threat perception. We also found some evidence of direct effects of uncertainty on conspiracy beliefs and indirect effects through threat perception and serially mediated through threat perception and negative emotions. Findings suggest that effects - either direct or indirect - of uncertainty on conspiratorial thinking/conspiracy beliefs are moderated by perceived relevance to COVID-19, personal experience of the disease, and social media use. Theoretical and practical implications of these findings are discussed.
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COVID-19 , Humanos , COVID-19/epidemiologia , Incerteza , Saúde Pública , EmoçõesRESUMO
The japonica rice (Oryza sativa L.) cultivar Koshihikari is considered an important breeding material with good eating quality (EQ). To effectively utilize Koshihikari in molecular breeding programs, determining its whole genome sequence including cultivar-specific segment is crucial. Here, the Koshihikari genome was sequenced using Nanopore and Illumina platforms, and de novo assembly was performed. A highly contiguous Koshihikari genome sequence was compared with Nipponbare, the reference genome of japonica. Genome-wide synteny was observed, as expected, without large structural variations. However, several gaps in alignment were detected on chromosomes 3, 4, 9, and 11. It was notable that previously identified EQ-related QTLs were found in these gaps. Moreover, sequence variations were identified in chromosome 11 at a region flanking the P5 marker, one of the significant markers of good EQ. The Koshihikari-specific P5 region was found to be transmitted through the lineage. High EQ cultivars derived from Koshihikari possessed P5 sequences; on the other hand, Koshihikari-derived low EQ cultivars didn't contain the P5 region, which implies that the P5 genomic region affects the EQ of Koshihikari progenies. The EQ of near-isogenic lines (NILs) of Samnam (a low EQ cultivar) genetic background harboring the P5 segment was improved compared to that of Samnam in Toyo taste value. The structure of the Koshihikari-specific P5 genomic region associated with good EQ was analyzed, which is expected to facilitate the molecular breeding of rice cultivars with superior EQ. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01335-3.
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KEY MESSAGE: Synchronous pod maturity is critical for increasing grain yield. The candidate genes involved in synchronous pod maturity were identified through RNA-seq and HPLC. Mungbean (Vigna radiata [L.] Wilczek), an important source of carbohydrate and protein in Asia, is characterized by nonsynchronous pod maturity; consequently, harvesting is labor intensive. Because pod maturity is associated with synthesis and remobilization of sucrose, we examined changes in sucrose levels and transcriptome in leaf (source) tissues after pod (sink) removal using two genotypes, VC1973A and V2984; VC1973A had higher synchronicity in pod maturity than V2984. After pod removal, much higher number of pods were produced in V2984 than VC1973A. The sucrose content of leaf tissues significantly decreased in V2984 because it continued to utilize assimilates from leaves for producing new pods, but significantly increased in VC1973A because of the loss of sink. Transcriptome analysis revealed that the number of differentially expressed genes was approximately fourfold higher in VC1973A than in those of V2984 after pod removal. The expression of two paralogous genes (Vradi01g05010 and Vradi10g08240), encoding beta-glucosidase enzymes, significantly decreased in VC1973A after pod removal and was significantly lower in depodded VC1973A than depodded V2984, indicating these two genes may participate in sucrose utilization for seed development by regulating the level of glucose. The results of this study will help elucidate the genetic basis of synchronous pod maturity in mungbean and facilitate the development of new cultivars with synchronous pod maturity.
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Folhas de Planta/genética , Sementes/genética , Sacarose/metabolismo , Transcriptoma/genética , Vigna/genética , Cromatografia Líquida de Alta Pressão , Regulação da Expressão Gênica de Plantas/genética , Ontologia Genética , Genótipo , Folhas de Planta/metabolismo , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Transdução de Sinais/genética , Amido/genética , Amido/metabolismo , Vigna/crescimento & desenvolvimento , Vigna/metabolismoRESUMO
Jatropha curcas (physic nut), a non-edible oilseed crop, represents one of the most promising alternative energy sources due to its high seed oil content, rapid growth and adaptability to various environments. We report ~339 Mbp draft whole genome sequence of J. curcas var. Chai Nat using both the PacBio and Illumina sequencing platforms. We identified and categorized differentially expressed genes related to biosynthesis of lipid and toxic compound among four stages of seed development. Triacylglycerol (TAG), the major component of seed storage oil, is mainly synthesized by phospholipid:diacylglycerol acyltransferase in Jatropha, and continuous high expression of homologs of oleosin over seed development contributes to accumulation of high level of oil in kernels by preventing the breakdown of TAG. A physical cluster of genes for diterpenoid biosynthetic enzymes, including casbene synthases highly responsible for a toxic compound, phorbol ester, in seed cake, was syntenically highly conserved between Jatropha and castor bean. Transcriptomic analysis of female and male flowers revealed the up-regulation of a dozen family of TFs in female flower. Additionally, we constructed a robust species tree enabling estimation of divergence times among nine Jatropha species and five commercial crops in Malpighiales order. Our results will help researchers and breeders increase energy efficiency of this important oil seed crop by improving yield and oil content, and eliminating toxic compound in seed cake for animal feed.
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Euphorbiaceae/enzimologia , Jatropha/enzimologia , Família Multigênica , Fósforo-Oxigênio Liases/metabolismo , Biocombustíveis , Mapeamento Cromossômico , Euphorbiaceae/genética , Euphorbiaceae/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Jatropha/genética , Jatropha/crescimento & desenvolvimento , Lipídeos/biossíntese , Anotação de Sequência Molecular , Ésteres de Forbol/metabolismo , Fósforo-Oxigênio Liases/genética , Filogenia , Melhoramento Vegetal , Óleos de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/enzimologia , Sementes/genética , Sementes/crescimento & desenvolvimentoRESUMO
The 2018 student debates of the Entomological Society of America were held at the Joint Annual Meeting for the Entomological Societies of America, Canada, and British Columbia in Vancouver, BC. Three unbiased introductory speakers and six debate teams discussed and debated topics under the theme 'Entomology in the 21st Century: Tackling Insect Invasions, Promoting Advancements in Technology, and Using Effective Science Communication'. This year's debate topics included: 1) What is the most harmful invasive insect species in the world? 2) How can scientists diffuse the stigma or scare factor surrounding issues that become controversial such as genetically modified organisms, agricultural biotechnological developments, or pesticide chemicals? 3) What new/emerging technologies have the potential to revolutionize entomology (other than Clustered Regularly Interspaced Short Palindromic Repeats)? Introductory speakers and debate teams spent approximately 9 mo preparing their statements and arguments and had the opportunity to share this at the Joint Annual Meeting with an engaged audience.
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Entomologia/tendências , Insetos , Animais , Biotecnologia , Espécies IntroduzidasRESUMO
High-intensity ultraviolet-B (UV-B) irradiation is a complex abiotic stressor resulting in excessive light exposure, heat, and dehydration, thereby affecting crop yields. In the present study, we identified quantitative trait loci (QTLs) for resistance to high-intensity UV-B irradiation in soybean (Glycine max [L.]). We used a genotyping-by-sequencing approach using an F6 recombinant inbred line (RIL) population derived from a cross between Cheongja 3 (UV-B sensitive) and Buseok (UV-B resistant). We evaluated the degree of leaf damage by high-intensity UV-B radiation in the RIL population and identified four QTLs, UVBR12-1, 6-1, 10-1, and 14-1, for UV-B stress resistance, together explaining 20% of the observed phenotypic variation. The genomic regions containing UVBR12-1 and UVBR6-1 and their syntenic blocks included other known biotic and abiotic stress-related QTLs. The QTL with the highest logarithm of odds (LOD) score of 3.76 was UVBR12-1 on Chromosome 12, containing two genes encoding spectrin beta chain, brain (SPTBN, Glyma.12g088600) and bZIP transcription factor21/TGACG motif-binding 9 (bZIP TF21/TGA9, Glyma.12g088700). Their amino acid sequences did not differ between the mapping parents, but both genes were significantly upregulated by UV-B stress in Buseok but not in Cheongja 3. Among five genes in UVBR6-1 on Chromosome 6, Glyma.06g319700 (encoding a leucine-rich repeat family protein) had two nonsynonymous single nucleotide polymorphisms differentiating the parental lines. Our findings offer powerful genetic resources for efficient and precise breeding programs aimed at developing resistant soybean cultivars to multiple stresses. Furthermore, functional validation of the candidate genes will improve our understanding of UV-B stress defense mechanisms.
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Glycine max/genética , Glycine max/efeitos da radiação , Locos de Características Quantitativas/genética , Tolerância a Radiação/genética , Raios Ultravioleta , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Cruzamentos Genéticos , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Ligação Genética , Genoma de Planta , Endogamia , Escore Lod , Fenótipo , Folhas de Planta/efeitos da radiação , Polimorfismo de Nucleotídeo Único/genética , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos da radiação , Sintenia/genéticaRESUMO
Large sequence insertion (LSI) is one of the structural variations (SVs) that may cause phenotypic differences in plants. To identify the LSIs using medium-coverage sequencing data of four wild soybean (Glycine soja) genotypes, we designed a hybrid approach combining de novo assembly and read mapping. Total reads and reads with both ends unmapped were independently assembled into "ordinary contigs" and "orphan contigs", respectively, and subjected to pairwise alignment and stringent filtering. This approach predicted 24 LSIs averaging 2682 bp in size, with no overlap with SVs detected by Pindel, BreakDancer, or ScanIndel, and they were validated by PCR. Compared with the soybean (Glycine max) reference genome, 20 LSIs were located outside genic regions. One of the four LSIs within a genic region, LSI05, is located in the coding DNA sequence region of a protein kinase superfamily gene (Glyma.08G123500). It caused delayed translation initiation and loss of 24 amino acids in the wild soybean genotype CW12. LSI05 was more frequently observed in 29 G. soja accessions than in 34 G. max accessions. Identified LSIs would be genomic resources harboring novel gene contents for studying SVs and improving crops. Moreover, our cost-efficient approach may be applicable to other plant species.
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Mapeamento de Sequências Contíguas/métodos , Glycine max/genética , Mutagênese Insercional , Análise de Sequência de DNA/métodos , Genoma de Planta , Variação Estrutural do Genoma , Genômica/métodos , Anotação de Sequência Molecular , Fenótipo , Melhoramento VegetalRESUMO
BACKGROUND: Proanthocyanidins are oligomeric or polymeric end products of flavonoid metabolic pathways starting with the central phenylpropanoid pathway. Although soybean (Glycine spp.) seeds represent a major source of nutrients for the human diet, as well as components for the cosmetics industry as a result of their high levels of flavonoid metabolites, including isoflavonoids, anthocyanins and proanthocyanidins, the genetic regulatory mechanisms underlying proanthocyanidin biosynthesis in soybean remain unclear. RESULTS: We evaluated interspecific and intraspecific variability in flavonoid components in soybean using 43 cultivars, landraces and wild soybean accessions. We performed transcriptomic profiling of genes encoding enzymes involved in flavonoid biosynthesis using three soybean genotypes, Hwangkeum (elite cultivar), IT109098 (landrace) and IT182932 (wild accession), in seeds. We identified a Glycine max landrace, IT109098, with a proanthocyanidin content as high as that of wild soybean. Different homologous genes for anthocyanidin reductase, which is involved in proanthocyanidin biosynthesis, were detected as differentially expressed genes between IT109098 and IT182932 compared to Hwangkeum. CONCLUSION: We detected major differences in the transcriptional levels of genes involved in the biosynthesis of proanthocyanidin and anthocyanin among genotypes beginning at the early stage of seed development. The results of the present study provide insights into the underlying genetic variation in proanthocyanidin biosynthesis among soybean genotypes. © 2017 Society of Chemical Industry.
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Regulação da Expressão Gênica de Plantas , Glycine max/genética , Proteínas de Plantas/genética , Proantocianidinas/biossíntese , Vias Biossintéticas , Glicina/metabolismo , Proteínas de Plantas/metabolismo , Sementes/genética , Sementes/metabolismo , Glycine max/metabolismo , TranscriptomaRESUMO
The use of next-generation sequencers and advanced genotyping technologies has propelled the field of plant genomics in model crops and plants and enhanced the discovery of hidden bridges between genotypes and phenotypes. The newly generated reference sequences of unstudied minor plants can be annotated by the knowledge of model plants via translational genomics approaches. Here, we reviewed the strategies of translational genomics and suggested perspectives on the current databases of genomic resources and the database structures of translated information on the new genome. As a draft picture of phenotypic annotation, translational genomics on newly sequenced plants will provide valuable assistance for breeders and researchers who are interested in genetic studies.
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Produtos Agrícolas/genética , Genoma de Planta , Genômica/métodos , Melhoramento Vegetal/métodos , Mapeamento Cromossômico , Bases de Dados Genéticas , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
BACKGROUND: Fatty liver is the hepatic manifestation of metabolic syndrome (MetS) and is a known risk factor for colorectal neoplasia (CRN). Gallbladder (GB) polyps share many common risk factors with CRN. However, studies evaluating CRN risk according to fatty liver severity and the presence of GB polyps are rare. AIM: To investigate CRN risk according to the fatty liver severity and the presence of GB polyps. METHODS: A retrospective cross-sectional study was performed on 44,220 participants undergoing colonoscopy and abdominal ultrasonography (US) as part of a health-screening program. RESULTS: Of the participants, fatty liver was diagnosed as mild in 27.7 %, moderate in 5.1 %, and severe in 0.4 % and 13.4 % were diagnosed with GB polyps. Mean age of participants was 42.7 years. In adjusted models, risk of overall CRN and non-advanced CRN increased with worsening fatty liver severity (P for trend = 0.007 and 0.020, respectively). Adjusted odd ratios for overall CRN and non-advanced CRN comparing participants with mild, moderate, and severe fatty liver to participants without fatty liver were 1.13 and 1.12 for mild, 1.12 and 1.10 for moderate, and 1.56 and 1.65 for severe. The presence of GB polyps did not correlate with CRN risk after adjusting for confounders. CONCLUSIONS: CRN risk increased with worsening fatty liver severity. However the association between GB polyp and CRN was not significant in the presence of other variables. Considering that many people undergo noninvasive abdominal US as a health screen, our study will contribute to colonoscopy screening strategies in people undergoing abdominal US.
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Pólipos Adenomatosos/epidemiologia , Pólipos do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Doenças da Vesícula Biliar/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Pólipos/epidemiologia , Pólipos Adenomatosos/patologia , Adulto , Distribuição de Qui-Quadrado , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Estudos Transversais , Feminino , Doenças da Vesícula Biliar/diagnóstico por imagem , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Razão de Chances , Pólipos/diagnóstico por imagem , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , UltrassonografiaRESUMO
Jasmonic acid (JA) functions in plant development, including senescence and immunity. Arabidopsis thaliana CORONATINE INSENSITIVE 1 encodes a JA receptor and functions in the JA-responsive signaling pathway. The Arabidopsis genome harbors a single COI gene, but the rice (Oryza sativa) genome harbors three COI homologs, OsCOI1a, OsCOI1b, and OsCOI2. Thus, it remains unclear whether each OsCOI has distinct, additive, synergistic, or redundant functions in development. Here, we use the oscoi1b-1 knockout mutants to show that OsCOI1b mainly affects leaf senescence under senescence-promoting conditions. oscoi1b-1 mutants stayed green during dark-induced and natural senescence, with substantial retention of chlorophylls and photosynthetic capacity. Furthermore, several senescence-associated genes were downregulated in oscoi1b-1 mutants, including homologs of Arabidopsis thaliana ETHYLENE INSENSITIVE 3 and ORESARA 1, important regulators of leaf senescence. These results suggest that crosstalk between JA signaling and ethylene signaling affects leaf senescence. The Arabidopsis coi1-1 plants containing 35S:OsCOI1a or 35S:OsCOI1b rescued the delayed leaf senescence during dark incubation, suggesting that both OsCOI1a and OsCOI1b are required for promoting leaf senescence in rice. oscoi1b-1 mutants showed significant decreases in spikelet fertility and grain weight, leading to severe reduction of grain yield, indicating that OsCOI1-mediated JA signaling affects spikelet fertility and grain filling.
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Mutação/genética , Oryza/genética , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/genética , Acetatos/farmacologia , Ciclopentanos/farmacologia , Escuridão , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Técnicas de Inativação de Genes , Genes de Plantas , Teste de Complementação Genética , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Oxilipinas/farmacologia , Fenótipo , Filogenia , Reguladores de Crescimento de Plantas/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/ultraestrutura , Proteínas de Plantas/metabolismo , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Homologia de Sequência do Ácido NucleicoRESUMO
In this study, we investigated the brittle fracture behavior of Sn-3.0Ag-0.5Cu (SAC305) solder joints with a Direct Electroless Gold (DEG) surface finish, formed using laser-assisted bonding (LAB) and mass reflow (MR) techniques. Commercial SAC305 solder balls were used to ensure consistency. LAB increases void fractions and coarsens the primary ß-Sn phase with higher laser power, resulting in a larger eutectic network area fraction. In contrast, MR produces solder joints with minimal voids and a thicker intermetallic compound (IMC) layer. LAB-formed joints exhibit higher high-speed shear strength and lower brittle fracture rates compared to MR. The key factor in the reduced brittle fracture in LAB joints is the thinner IMC layer at the joint interface. This study highlights the potential of LAB in enhancing the mechanical reliability of solder joints in advanced electronic packaging applications.
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The mumps virus (MuV) causes a highly contagious human disease characterized by swelling of the parotid glands. Although the administration of an attenuated Jeryl Lynn (JL) MuV vaccine shows efficacy in reducing the incidence of MuV infection, sporadic mumps outbreaks still occur in vaccinated populations. We have previously established that an inactivated F genotype mumps vaccine has a higher neutralizing antibody titer against diverse circulating mumps viruses in mice. Here, we aimed to develop a vaccination strategy to enhance the immune response for MuV and assess the effects of heterologous vaccination compared with homologous approaches. We administered an inactivated F genotype mumps vaccine booster following a homologous prime-boost regime and compared its efficacy with three doses of homologous JL vaccine in mice. We demonstrated robust stimulation of neutralizing antibodies and cellular immune response of interferon-γ-secreting cytotoxic T cells following administration of an inactivated F genotype mumps vaccine booster after a homologous prime-boost regime with JL. Compared with the homologous prime-boost regime, this heterologous prime-boost regime showed protective efficacy against the F genotype of MuV. These findings suggest that the heterologous vaccination strategy based on the administration of an inactivated F genotype mumps vaccine provides more effective cross-protection against circulating wild-type mumps viruses than homologous vaccination.
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OBJECTIVE: Non-invasive, pill-sized capsules can provide intestinal fluid sampling to easily retrieve site-specific gut microbiome samples for studies in nutrition and chronic diseases. However, capsules with both automatic sampling and active locomotion are uncommon due to limited onboard space. This paper presents a novel hybrid hydrogel-magnet actuated capsule featuring: i) pH-responsive hydrogels that will automatically trigger fluid sampling at an environmental pH of > 6 and ii) active locomotion by an external rotating magnetic field. METHOD: Two capsule designs were fabricated (Design A: 31 µL sampling volume with dimensions 8 mm × 19 mm, Design B: 41 µL sampling volume with dimensions 8 mm × 21 mm). They were immersed in simulated gastric (pH = 1.2) and simulated intestinal fluid (pH = 6.8) to test for automatic intestinal fluid sampling. An external rotating magnetic field was applied to test for active locomotion. Finally, seal tests were performed to demonstrate sample contamination mitigation. RESULTS: Preliminary experiments showed that sampling occurred quickly and automatically in simulated intestinal fluid at 6 - 15 hours, active locomotion via rotation, rolling, and tumbling were possible at magnetic field magnitudes < 10 mT, oil piston seals were better at mitigating sample contamination than water piston seals, and minimum o-ring seal pressures limits of 1.95 and 1.69 kPa for Design A and B respectively were sufficient against intra-abdominal pressures. SIGNIFICANCE: This work presents the ability to impart capsule multi-functionality in a compact manner without onboard electronics or external triggering for sampling.
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Mumps virus (MuV) causes an acute contagious human disease characterized by swelling of the parotid glands. Despite the near elimination of mumps in many countries, the disease has recurred, even in vaccinated populations, especially adolescents. Immunization effectivity of the genotype A vaccine strain Jeryl Lynn (JL) is declining as genotype A is no longer predominant; therefore, a new vaccine strain and booster vaccine are required. We generated a cell culture-adapted MuV genotype F called F30 and evaluated its immunogenicity and cross-protective activity against diverse genotypes. F30 genome nucleotide sequence determination revealed changes in the NP, L, SH, and HN genes, leading to five amino acid changes compared to a minimally passaged stock (F10). F30 showed delayed growth, smaller plaque size in Vero cells, and lower neurotoxicity in neonatal mice than F10. Furthermore, F30 was immunogenic to other genotypes, including the JL vaccine strain, with higher efficacy than that of JL for homologous and heterologous immunization. Further, F30 exhibited cross-protective immunity against MuV genotypes F and G in Ifnar-/- mice after a third immunization with F30 following two doses of JL. Our data suggest that the live-attenuated virus F30 could be an effective booster vaccine to control breakthrough infections and mumps epidemics.
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Introduction: Sweetpotato faces breeding challenges due to physiological and genomic issues. Gamma radiation is a novel approach for inducing genetic variation in crops. We analyzed the transcriptomic changes in gamma ray-induced sweetpotato mutants with altered stem development compared with those in the wild-type 'Tongchaeru' cultivar. Methods: RNA sequencing analyses were performed to identify changes in the expression of genes related to stem development. Results: Transcriptomic analysis identified 8,931 upregulated and 6,901 downregulated genes, including the upregulation of the auxin-responsive SMALL AUXIN UP RNA (SAUR) and three PHYTOCHROME INTERACTING FACTOR 4 (PIF4) genes. PIF4 is crucial for regulating the expression of early auxin-responsive SAUR genes and stem growth in Arabidopsis thaliana. In the mutant, several genes related to stem elongation, including PIF4 and those involved in various signaling pathways such as auxin and gibberellin, were upregulated. Discussion: Our results suggest that gamma ray-induced mutations influence auxin-dependent stem development by modulating a complex regulatory network involving the expression of PIF4 and SAUR genes, and other signaling pathways such as gibberellin and ethylene signaling genes. This study enhances our understanding of the regulatory mechanisms underlying stem growth in sweetpotato, providing valuable insights for genomics-assisted breeding efforts.
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Global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron subvariants, such as BA.4, BA.5 and XBB.1.5, has been leading the recent wave of coronavirus disease 2019 (COVID-19). Unique mutations in the spike proteins of these emerging Omicron subvariants caused immune evasion from the pre-existing protective immunity induced by vaccination or natural infection. Previously, we developed AdCLD-CoV19-1, a non-replicating recombinant adenoviral vector that encodes the receptor binding domain of the spike protein of the ancestral SARS-CoV-2 strain. Based on the same recombinant adenoviral vector platform, updated vaccines that cover unique mutations found in each Omicron subvariant, including BA.1, BA.2, BA.4.1 and BA.5, were constructed. Preclinical studies revealed that each updated vaccine as a booster shot following primary vaccination targeting the ancestral strain improved neutralizing antibody responses against the pseudovirus of its respective strain most effectively. Of note, boosting with a vaccine targeting the BA.1 or BA.2 Omicron subvariant was most effective in neutralization against the pseudovirus of the BA.2.75 strain, whereas BA.4.1/5-adapted booster shots were most effective in neutralization against the BQ.1, BQ1.1 and BF.7 strains. Therefore, it is imperative to develop a vaccination strategy that can cover the unique spike mutations of currently circulating Omicron subvariants in order to prevent the next wave of COVID-19.
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COVID-19 , SARS-CoV-2 , Animais , Camundongos , SARS-CoV-2/genética , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Vetores Genéticos , Adenoviridae/genéticaRESUMO
mRNA vaccines against SARS-CoV-2 have revolutionized vaccine development, but their immunological mechanisms are not fully understood. Here, we investigate injection site responses of mRNA vaccines by generating a comprehensive single-cell transcriptome profile upon lipid nanoparticle (LNP) or LNP-mRNA challenge in female BALB/c mice. We show that LNP-induced stromal pro-inflammatory responses and mRNA-elicited type I interferon responses dominate the initial injection site responses. By tracking the fate of delivered mRNA, we discover that injection site fibroblasts are highly enriched with the delivered mRNA and that they express IFN-ß specifically in response to the mRNA component, not to the LNP component of mRNA vaccines. Moreover, the mRNA-LNP, but not LNP alone, induces migratory dendritic cells highly expressing IFN-stimulated genes (mDC_ISGs) at the injection site and draining lymph nodes. When co-injected with LNP-subunit vaccine, IFN-ß induces mDC_ISGs at the injection site, and importantly, it substantially enhances antigen-specific cellular immune responses. Furthermore, blocking IFN-ß signaling at the injection site significantly decreases mRNA vaccine-induced cellular immune responses. Collectively, these data highlight the importance of injection site fibroblasts and IFN-ß signaling during early immune responses against the mRNA vaccine and provide detailed information on the initial chain of immune reactions elicited by mRNA vaccine injection.
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Células Dendríticas , Fibroblastos , Imunidade Celular , Imunidade Inata , Interferon beta , Camundongos Endogâmicos BALB C , Nanopartículas , Vacinas de mRNA , Animais , Interferon beta/imunologia , Interferon beta/metabolismo , Feminino , Imunidade Inata/imunologia , Imunidade Inata/efeitos dos fármacos , Camundongos , Vacinas de mRNA/imunologia , Células Dendríticas/imunologia , Nanopartículas/química , Fibroblastos/imunologia , Fibroblastos/metabolismo , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2/imunologia , Lipídeos/química , COVID-19/prevenção & controle , COVID-19/imunologia , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Análise de Célula Única , LipossomosRESUMO
(1) Background: Remifentanil is used for intraoperative pain control; however, it has several side effects, such as hypotension and opioid-induced hyperalgesia. We aimed to determine whether an intraoperative remifentanil infusion may increase postoperative opioid consumption in patients undergoing total knee arthroscopy (TKA) under femoral nerve block (FNB) in addition to general anesthesia. (2) Methods: We randomly assigned 66 patients who underwent total knee arthroplasty to the remifentanil (R) and control (C) groups. All patients underwent FNB and popliteal artery and posterior capsule of the knee (iPACK) block in addition to sevoflurane-based general anesthesia. Postoperative pain control was achieved using intravenous patient-controlled analgesia (IV-PCA) fentanyl. We recorded IV-PCA fentanyl consumption at various postoperative timepoints, numerical rating scale (NRS) scores, intraoperative changes in vital signs and index of nociception (qNOX), ephedrine consumption, postoperative side effects, satisfaction, and sleep quality. (3) Results: The primary outcome (the cumulative IV-PCA fentanyl usage within 48 h postoperatively) was significantly lower in the C group (541.1 ± 294.5 µg) than in the R group (717.5 ± 224.0 µg) (p < 0.001). The secondary outcome (the cumulative IV-PCA fentanyl usage within 12, 24, and 72 h) was lower in the C group than in the R group and the mean arterial pressure was lower in the R group than in the C group from immediately after tourniquet on to immediately after tourniquet off. The heart rate was lower in the R group from immediately after incision to immediately after irrigation. There was no significant between-group difference in the perioperative qNOX and NRS scores at rest and activity except for NRS scores at 72 h postoperatively. Ephedrine use was higher in the R group than in the C group (p = 0.003). There was no significant between-group difference in the incidence of postoperative nausea and vomiting, nor in the postoperative satisfaction and sleep quality. (4) Conclusions: Avoiding intraoperative remifentanil infusion may reduce total opioid consumption in patients undergoing FNB before TKA.