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Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.
Assuntos
Receptores Acoplados a Proteínas G , Transdução de Sinais , Humanos , Aminas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Esquizofrenia/metabolismoRESUMO
Small nuclear RNAs (snRNAs) are structural and functional cores of the spliceosome. In metazoan genomes, each snRNA has multiple copies/variants, up to hundreds in mammals. However, the expressions and functions of each copy/variant in one organism have not been systematically studied. Focus on U1 snRNA genes, we investigated all five copies in Drosophila melanogaster using two series of constructed strains. Analyses of transgenic flies that each have a U1 promoter-driven gfp revealed that U1:21D is the major and ubiquitously expressed copy, and the other four copies have specificities in developmental stages and tissues. Mutant strains that each have a precisely deleted copy of U1-gene exhibited various extents of defects in fly morphology or mobility, especially deletion of U1:82Eb. Interestingly, splicing was changed at limited levels in the deletion strains, while large amounts of differentially-expressed genes and alternative polyadenylation events were identified, showing preferences in the down-regulation of genes with 1-2 introns and selection of proximal sites for 3'-end polyadenylation. In vitro assays suggested that Drosophila U1 variants pulled down fewer SmD2 proteins compared to the canonical U1. This study demonstrates that all five U1-genes in Drosophila have physiological functions in development and play regulatory roles in transcription and 3'-end formation.
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Drosophila melanogaster , RNA Nuclear Pequeno , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , RNA Nuclear Pequeno/genética , RNA Nuclear Pequeno/metabolismo , Splicing de RNA/genética , Drosophila/genética , Drosophila/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mamíferos/genéticaRESUMO
Pleiotropy, the phenomenon in which a single gene influences multiple traits, is a fundamental concept in genetics. However, the evolutionary mechanisms underlying pleiotropy require further investigation. In this study, we conducted parallel gene knockouts targeting 100 transcription factors in two strains of Saccharomyces cerevisiae. We systematically examined and quantified the pleiotropic effects of these knockouts on gene expression levels for each transcription factor. Our results showed that the knockout of a single gene generally affected the expression levels of multiple genes in both strains, indicating various degrees of pleiotropic effects. Strikingly, the pleiotropic effects of the knockouts change rapidly between strains in different genetic backgrounds, and â¼85% of them were non-conserved. Further analysis revealed that the conserved effects tended to be functionally associated with the deleted transcription factors, while the non-conserved effects appeared to be more ad hoc responses. In addition, we measured 184 yeast cell morphological traits in these knockouts and found consistent patterns. In order to investigate the evolutionary processes underlying pleiotropy, we examined the pleiotropic effects of standing genetic variations in a population consisting of â¼1000 hybrid progenies of the two strains. We observed that newly evolved expression quantitative trait loci (eQTLs) impacted the expression of a greater number of genes than did old eQTLs, suggesting that natural selection is gradually eliminating maladaptive or slightly deleterious pleiotropic responses. Overall, our results show that, although being prevalent for new mutations, the majority of pleiotropic effects observed are evolutionarily transient, which explains how evolution proceeds despite complicated pleiotropic effects.
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BACKGROUND: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. RESULTS: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. CONCLUSION: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.
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Galinhas , Domesticação , Homozigoto , Animais , Galinhas/genética , Seleção Genética , Locos de Características Quantitativas , Genoma , Genômica/métodos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
To improve the durability of the photobioreactor antibiofouling surface for microalgal cultivation, a series of photoreactive poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) were successfully synthesized and used to modify ethylene-vinyl acetate (EVA) films by a surface coating and UV light grafting method. Fourier transform infrared (FT-IR) spectra, X-ray photoelectron spectroscopy analysis (XPS) and fluorescence microscopy results indicated that PTFEMA were fixed successfully onto the EVA film surface through a covalent bond. During the microalgal adhesion assay, the number of EVA-PTFEMA film-adhered microalgae was 41.4% lower than that of the EVA film. Moreover, the number of microalgae attached to the EVA-PTFEMA film decreased by 61.7% after cleaning, while that of EVA film decreased by only 49.1%. It was found that the contact angle of EVA-PTFEMA film surface increased, and remained stable when immersed in acid and alkali solution for up to 90 days. HIGHLIGHTSDurable photobioreactor antibiofouling surfaces for microalgal cultivation were prepared successfully.The contact angle of antibiofouling coating surface remained stable in acid and base environment for 90 days.The attached microalgae on antibiofouling surface decreased 41.4% than those of unmodified surface.The attached microalgae on antibiofouling surface could be cleaned by 61.7% through changing the flow velocity of microalgal suspension.
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In this study, a microcosm experiment was conducted to investigate the effects of Na2S2O8 preoxidation combined with biostimulation on petroleum-contaminated soil remediation. The response of microbial community during this process was explored using BIOLOG ECO microplate carbon utilization method and 16â¯s rDNA high-throughput sequencing. The results showed that use of 10â¯mg/g Na2S2O8 removed 19.8â¯% of the petroleum hydrocarbons, reduced soil biotoxicity and did not affect soil microbial activity compared to other concentrations. Therefore, sodium persulfate of ca. 10â¯mg/g was used to oxidize petroleum in soil before the biostimulation experiment with organic and inorganic fertilizers. Our finding showed that the content of total petroleum hydrocarbons (TPHs) in soil was reduced by 43.3â¯% in inorganic fertilizer treatment after 60 days. The results of BIOLOG ECO microplate carbon utilization analysis and 16â¯S rDNA high-throughput sequencing further confirmed that biostimulation quickly restored the microbial activities in oxidant treated soil. The main marker bacteria in chemical oxidation combined with biostimulation remediation were Arthrobacter and Paenarthrobacter, and their relative abundances were both significantly negatively correlated with the content of petroleum hydrocarbons in soil.
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Biodegradação Ambiental , Oxirredução , Petróleo , Microbiologia do Solo , Poluentes do Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Fertilizantes/análise , Sulfatos , Hidrocarbonetos , Compostos de Sódio/toxicidade , Solo/química , Arthrobacter , Recuperação e Remediação Ambiental/métodos , Bactérias/efeitos dos fármacos , Bactérias/genéticaRESUMO
A vast and painful price has been paid in the battle against viruses in global health [...].
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Antivirais , Descoberta de Drogas , Antivirais/farmacologia , Antivirais/uso terapêutico , Descoberta de Drogas/métodos , Humanos , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacosRESUMO
Circadian rhythm disorders pose major risks to human health and animal production activity, and the hypothalamus is the center of circadian rhythm regulation. However, the epigenetic regulation of circadian rhythm based on farm animal models has been poorly investigated. We collected chicken hypothalamus samples at seven time points in one light/dark cycle and performed long noncoding RNA (lncRNA), circular RNA (circRNA), and mRNA sequencing to detect biomarkers associated with circadian rhythm. We enhanced the comprehensive expression profiling of ncRNAs and mRNAs in the hypothalamus and found two gene sets (circadian rhythm and retinal metabolism) associated with the light/dark cycle. Noncoding RNA networks with circadian expression patterns were identified by differential expression and circadian analysis was provided that included 38 lncRNAs, 15 circRNAs, and 200 candidate genes. Three lncRNAs (ENSGALT00000098661, ENSGALT00000100816, and MSTRG.16980.1) and one circRNA (novel_circ_010168) in the ncRNA-mRNA regulatory network were identified as key molecules influencing circadian rhythm by regulating AOX1 in retinal metabolism. These ncRNAs were predicted to be related to pernicious anemia, gonadal, eye disease and other disorders in humans. Together, the findings of this study provide insights into the epigenetic mechanisms of circadian rhythm and reveal AOX1 as a promising target of circadian rhythm regulation.
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RNA Longo não Codificante , Animais , Humanos , RNA Longo não Codificante/genética , Epigênese Genética , RNA Circular/genética , Ritmo Circadiano/genética , RNA Mensageiro/genéticaRESUMO
Saline and alkaline stresses limit plant growth and reduce crop yield. Soil salinization and alkalization seriously threaten the sustainable development of agriculture and the virtuous cycle of ecology. Biofertilizers made from plant growth-promoting rhizobacteria (PGPR) not only enhance plant growth and stress tolerance, but also are environmentally friendly and cost-effective. There have been many studies on the mechanisms underlying PGPRs enhancing plant salt resistance. However, there is limited knowledge about the interaction between PGPR and plants under alkaline-sodic stress. To clarify the mechanisms underlying PGPR's improvement of plants' tolerance to alkaline-sodic stress, we screened PGPR from the rhizosphere microorganisms of local plants growing in alkaline-sodic land and selected an efficient strain, Bacillus altitudinis AD13-4, as the research object. Our results indicate that the strain AD13-4 can produce various growth-promoting substances to regulate plant endogenous hormone levels, cell division and differentiation, photosynthesis, antioxidant capacity, etc. Transcriptome analysis revealed that the strain AD13-4 significantly affected metabolism and secondary metabolism, signal transduction, photosynthesis, redox processes, and plant-pathogen interactions. Under alkaline-sodic conditions, inoculation of the strain AD13-4 significantly improved plant biomass and the contents of metabolites (e.g., soluble proteins and sugars) as well as secondary metabolites (e.g., phenols, flavonoids, and terpenoids). The 16S rRNA gene sequencing results indicated that the strain AD13-4 significantly affected the abundance and composition of the rhizospheric microbiota and improved soil activities and physiochemical properties. Our study provides theoretical support for the optimization of saline-alkali-tolerant PGPR and valuable information for elucidating the mechanism of plant alkaline-sodic tolerance.
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Bacillus , Medicago sativa , Rizosfera , Microbiologia do Solo , Medicago sativa/microbiologia , Medicago sativa/crescimento & desenvolvimento , Bacillus/genética , Bacillus/fisiologia , Álcalis , Microbiota , Estresse Fisiológico , Tolerância ao Sal , Solo/químicaRESUMO
Inspired by our previous work on the modification of diarylpyrimidine-typed non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the reported crystallographic studies, a series of novel amino acids (analogues)-substituted thiophene[3,2-d]pyrimidine derivatives were designed and synthesized by targeting the solvent-exposed region of the NNRTI-binding pocket. The biological evaluation results showed that compound 5k was the most active inhibitor, exhibiting moderate-to-excellent potency against HIV-1 wild-type (WT) and a panel of NNRTI-resistant strains, with EC50 values ranging from 0.042 µM to 7.530 µM. Of special note, 5k exhibited the most potent activity against single-mutant strains (K103N and E138K), with EC50 values of 0.031 µM and 0.094 µM, being about 4.3-fold superior to EFV (EC50 = 0.132 µM) and 1.9-fold superior to NVP (EC50 = 0.181 µM), respectively. In addition, 5k demonstrated lower cytotoxicity (CC50 = 27.9 µM) and higher selectivity index values. The HIV-1 reverse transcriptase (RT) inhibition assay was further performed to confirm their binding target. Moreover, preliminary structure-activity relationships (SARs) and molecular docking studies were also discussed in order to provide valuable insights for further structural optimizations. In summary, 5k turned out to be a promising NNRTI lead compound for further investigations of treatments for HIV-1 infections.
Assuntos
Aminoácidos , Fármacos Anti-HIV , Desenho de Fármacos , Transcriptase Reversa do HIV , HIV-1 , Pirimidinas , Inibidores da Transcriptase Reversa , Tiofenos , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/síntese química , Transcriptase Reversa do HIV/antagonistas & inibidores , Transcriptase Reversa do HIV/metabolismo , HIV-1/efeitos dos fármacos , HIV-1/enzimologia , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/síntese química , Humanos , Tiofenos/farmacologia , Tiofenos/química , Tiofenos/síntese química , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/síntese química , Relação Estrutura-Atividade , Aminoácidos/química , Simulação de Acoplamento MolecularRESUMO
HIV-1 reverse transcriptase (RT) is considered as one of the most significant targets for the anti-HIV-1 drug design due to their determined mechanism and well-decoded crystal structure. As a part of our continuous efforts towards the development of potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) by exploiting the tolerant region I of NNRTIs binding pocket (NNIBP), the miniaturized parallel synthesis via CuAAC click chemistry reaction followed by in situ biological screening have been performed in this work. The in situ enzyme inhibition screening results showed that 14 compounds exhibited higher or equivalent inhibitory activity compared to the lead K-5a2 and ETR. Anti-HIV-1 activity results indicated that C1N51 displayed the most potent activity (EC50 = 0.01-0.26 µM) against wild-type and a panel of NNRTIs-resistant strains. Moreover, the molecular simulation demonstrated that the newly introduced triazole ring could develop new hydrogen bonds with Lys103 and Pro236, which explained the feasibility of introducing triazole in the tolerant region I of the RT binding pocket.
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Fármacos Anti-HIV , HIV-1 , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/química , Triazóis/farmacologia , Triazóis/química , Química Click , Desenho de Fármacos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/química , Transcriptase Reversa do HIV , Compostos Heterocíclicos com 1 Anel , Relação Estrutura-AtividadeRESUMO
This study presents proof of concept for designing a novel HIV-1 covalent inhibitor targeting the highly conserved Tyr318 in the HIV-1 non-nucleoside reverse transcriptase inhibitors binding pocket to improve the drug resistance profiles. The target inhibitor ZA-2 with a fluorosulfate warhead in the structure was found to be a potent inhibitor (EC50 = 11-246 nM) against HIV-1 IIIB and a panel of NNRTIs-resistant strains, being far superior to those of NVP and EFV. Moreover, ZA-2 was demonstrated with lower cytotoxicity (CC50 = 125 µM). In the reverse transcriptase inhibitory assay, ZA-2 exhibited an IC50 value of 0.057 µM with the ELISA method, and the MALDI-TOF MS data demonstrated the covalent binding mode of ZA-2 with the enzyme. Additionally, the molecular simulations have also demonstrated that compounds can form covalent binding to the Tyr318.
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Fármacos Anti-HIV , HIV-1 , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/química , HIV-1/metabolismo , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/química , Transcriptase Reversa do HIV/metabolismo , Desenho de Fármacos , Relação Estrutura-AtividadeRESUMO
Ultra-low molecular weight (ULMW) CO2 -polyols with well-defined hydroxyl end groups represent useful soft segments for the preparation of high-performance polyurethane foams. However, owing to the poor proton tolerance of catalysts towards CO2 /epoxide telomerization, it remains challenging to synthesize ULMW yet colorless CO2 -polyols. Herein, we propose an immobilization strategy of constructing supported catalysts by chemical anchoring of aluminum porphyrin on Merrifield resin. The resulting supported catalyst displays both extremely high proton tolerance (≈8000â times the equivalents of metal centers) and independence of cocatalyst, affording CO2 -polyols with ULMW (580â g mol-1 ) and high polymer selectivity (>99 %). Moreover, the ULMW CO2 -polyols with various architectures (tri-, quadra-, and hexa-arm) can be obtained, suggesting the wide proton universality of supported catalysts. Notably, benefiting from the heterogeneous nature of the supported catalyst, colorless products can be facilely achieved by simple filtration. The present strategy provides a platform for the synthesis of colorless ULMW polyols derived from not only CO2 /epoxides, but also lactone, anhydrides etc. or their combinations.
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Carbonic anhydrase XIV (Car14) is highly expressed in the hepatocyte, with predominance in the canalicular membrane and its active site in the extracellular milieu. The aim of this study is to determine the physiological relevance of Car14 for biliary fluid and acid/base output, as well as its role in the maintenance of hepatocellular and cholangiocyte integrity. The common bile duct of anesthetized car14-/- and car14+/+ mice was cannulated and hepatic HCO3- output was measured by microtitration and bile flow gravimetrically before and during stimulation with intravenously applied tauroursodeoxycholic acid (TUDCA). Morphological alterations and hepatic damage were assessed histologically and immunohistochemically in liver tissue from 3- to 52-week-old car14-/- and car14+/+ mice, and gene and/or protein expression was measured for pro-inflammatory cytokines, fibrosis, and cholangiocyte markers. Biliary basal and more so TUDCA-stimulated HCO3- output were significantly reduced in car14-/- mice of all age groups, whereas bile flow and hepatic and ductular morphology were normal at young age. Car14-/- mice developed fibrotic and proliferative changes in the small bile ducts at advanced age, which was accompanied by a reduction in bile flow, and an upregulation of hepatic cytokeratin 19 mRNA and protein expression. Membrane-bound Car14 is essential for biliary HCO3- output, and its loss results in gradual development of small bile duct disease and hepatic fibrosis. Bile flow is not compromised in young adulthood, suggesting that Car14-deficient mice may be a model to study the protective role of biliary canalicular HCO3- against luminal noxi to the cholangiocyte.
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Bicarbonatos , Ductos Biliares , Animais , Bicarbonatos/metabolismo , Ductos Biliares/metabolismo , Anidrases Carbônicas , Proliferação de Células , Fígado/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , CamundongosRESUMO
The activity of a gene newly integrated into a chromosome depends on the genomic context of the integration site. This "position effect" has been widely reported, although the other side of the coin, that is, how integration affects the local chromosomal environment, has remained largely unexplored, as have the mechanism and phenotypic consequences of this "externality" of the position effect. Here, we examined the transcriptome profiles of approximately 250 Saccharomyces cerevisiae strains, each with GFP integrated into a different locus of the wild-type strain. We found that in genomic regions enriched in essential genes, GFP expression tended to be lower, and the genes near the integration site tended to show greater expression reduction. Further joint analysis with public genome-wide histone modification profiles indicated that this effect was associated with H3K4me2. More importantly, we found that changes in the expression of neighboring genes, but not GFP expression, significantly altered the cellular growth rate. As a result, genomic loci that showed high GFP expression immediately after integration were associated with growth disadvantages caused by elevated expression of neighboring genes, ultimately leading to a low total yield of GFP in the long run. Our results were consistent with competition for transcriptional resources among neighboring genes and revealed a previously unappreciated facet of position effects. This study highlights the impact of position effects on the fate of exogenous gene integration and has significant implications for biological engineering and the pathology of viral integration into the host genome.
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Efeitos da Posição Cromossômica , Mutagênese Insercional , Transcriptoma , Aptidão Genética , Código das Histonas , Saccharomyces cerevisiaeRESUMO
The plant Shaker K+ channel AtAKT2 has been identified as a weakly rectifying channel that can stabilize membrane potentials to promote photoassimilate phloem loading and translocation. Thus, studies on functional characterization and regulatory mechanisms of AtAKT2-like channels in crops are highly important for improving crop production. Here, we identified the rice OsAKT2 as the ortholog of Arabidopsis AtAKT2, which is primarily expressed in the shoot phloem and localized at the plasma membrane. Using an electrophysiological assay, we found that OsAKT2 operated as a weakly rectifying K+ channel, preventing H+ /sucrose-symport-induced membrane depolarization. Three critical amino acid residues (K193, N206, and S326) are essential to the phosphorylation-mediated gating change of OsAKT2, consistent with the roles of the corresponding sites in AtAKT2. Disruption of OsAKT2 results in delayed growth of rice seedlings under short-day conditions. Interestingly, the lipid second messenger phosphatidic acid (PA) inhibits OsAKT2-mediated currents (both instantaneous and time-dependent components). Lipid dot-blot assay and liposome-protein binding analysis revealed that PA directly bound with two adjacent arginine residues in the ANK domain of OsAKT2, which is essential to PA-mediated inhibition of OsAKT2. Electrophysiological and phenotypic analyses also showed the PA-mediated inhibition of AtAKT2 and the negative correlation between intrinsic PA level and Arabidopsis growth, suggesting that PA may inhibit AKT2 function to affect plant growth and development. Our results functionally characterize the Shaker K+ channel OsAKT2 and reveal a direct link between phospholipid signaling and plant K+ channel modulation.
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Arabidopsis/genética , Oryza/genética , Ácidos Fosfatídicos/metabolismo , Canais de Potássio/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Membrana Celular/metabolismo , Oryza/metabolismo , Canais de Potássio/genética , Plântula/genética , Plântula/metabolismoRESUMO
Rice leaf angle is an important agronomic trait determining plant architecture and crop yield. Brassinosteroids (BRs) play crucial roles in controlling rice leaf angle, thus an increasing number of researches were focused on the BR signaling pathway in rice. However, the orthologs of some important components in Arabidopsis BR signaling have not yet been characterized in rice. In this study, we identified a rice bHLH transcription factor named OsBIM1, as the closest rice homolog of AtBIM1 (BES1-Interacting MYC-like Protein1). Overexpression of OsBIM1 significantly increases rice leaf angles, whereas the T-DNA knock-out mutant osbim1 and wide type (WT) showed similar leaf inclination. OsBIM1 overexpression enhances the sensitivity and response to BR treatment in rice. Gene expression analysis showed that the overexpression of OsBIM1 significantly increased the transcripts of INCREASED LEAF INCLINATION1 (OsILI1) that functions as a key transcription factor promoting BR signaling and response. Meanwhile, OsBIM1 inhibited the expression of DWARF2 (OsD2, a key enzyme in BR biosynthesis pathway). OsBIM1 can bind with OsILI1 promoter and enhance OsILI1 expression in response to BR treatment. The promoting effect of OsBIM1 overexpression on leaf angle can still be observed at harvest stage, but overexpression of OsBIM1 resulted in smaller grain size and reduced yield. These results indicate that OsBIM1 functions as a positive regulator in BR signaling, and its overexpression increases rice lamina inclination by promoting BR sensitivity and response.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Brassinosteroides/metabolismo , Oryza/crescimento & desenvolvimento , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Técnicas Genéticas , Oryza/genética , Oryza/metabolismo , Fenótipo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Transdução de SinaisRESUMO
Maintaining Na+ /K+ homeostasis is a critical feature for plant survival under salt stress, which depends on the operation of Na+ and K+ transporters. Although some K+ transporters mediating root K+ uptake have been reported to be essential to the maintenance of Na+ /K+ homeostasis, the effect of K+ long-distance translocation via phloem on plant salt tolerance remains unclear. Here, we provide physiological and genetic evidence of the involvement of phloem-localized OsAKT2 in rice salt tolerance. OsAKT2 is a K+ channel permeable to K+ but not to Na+ . Under salt stress, a T-DNA knock-out mutant, osakt2 and two CRISPR lines showed a more sensitive phenotype and higher Na+ accumulation than wild type. They also contained more K+ in shoots but less K+ in roots, showing higher Na+ /K+ ratios. Disruption of OsAKT2 decreases K+ concentration in phloem sap and inhibits shoot-to-root redistribution of K+ . In addition, OsAKT2 also regulates the translocation of K+ and sucrose from old leaves to young leaves, and affects grain shape and yield. These results indicate that OsAKT2-mediated K+ redistribution from shoots to roots contributes to maintenance of Na+ /K+ homeostasis and inhibition of root Na+ uptake, providing novel insights into the roles of K+ transporters in plant salt tolerance.
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Grão Comestível/genética , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Canais de Potássio/metabolismo , Potássio/metabolismo , Tolerância ao Sal , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Edição de Genes , Técnicas de Silenciamento de Genes , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/fisiologia , Floema/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Canais de Potássio/genética , Canais de Potássio/fisiologia , Tolerância ao Sal/genética , Tolerância ao Sal/fisiologiaRESUMO
Gastric cancer is the one of the most lethal malignancies of digestive system. Identifying molecular biomarkers is invaluable in help predicting clinical outcomes and developing targeted chemotherapies. GINS complex subunit 2 (GINS2) plays an essential role in the initiation and elongation of DNA replication. Although there have been studies revealing the prognostic significance of GINS2 in breast cancer and lung cancer, its involvement and function in gastric cancer need to be elucidated. We retrospectively enrolled a cohort of gastric adenocarcinoma patients after surgical resection (n = 123). By analyzing the mRNA and protein levels of GINS2 in tissue samples, we found that GINS2 presented a higher expression in tumor tissues than in adjacent normal stomach tissues. Besides, GINS2 level was positively correlated with tumor size and gastric adenocarcinoma tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower GINS2 showed a better overall survival compared to those with higher GINS2 expression. In addition, cellular and xenograft experiments confirmed the role of GINS2 in facilitating tumor proliferation both in vitro and in vivo. To our knowledge, this is the initial finding on GINS2 in promoting gastric adenocarcinoma progression. In conclusion, our study revealed a pro-oncogenic role of GINS2 in gastric cancer.
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Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Proliferação de Células , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/genéticaRESUMO
Nowadays, artificial construction of bacteria-algae consortia to enhance microalgal biomass is prevalent in enclosed systems, while few are built in an open culture. In this study, Achromobacter sp. and Rhizobium sp., isolated from an open pond of Chlorella sorokiniana, were the microalgal growth-promotion bacteria and selected to build the bacteria-algae consortia with axenic C. sorokiniana in open cultivation systems. To examine the performance of these two artificial bacteria-algae consortia in open culture under stable cultivation conditions, the co-cultivation experiments were conducted under constant temperature and light intensity indoors. It was found that Achromobacter sp. gradually lost the dominance of the population in the co-culture and failed to promote the growth of C. sorokiniana during open cultivation. However, the Rhizobium sp. maintained its dominant population of bacterial community in open culture and could promote the growth of C. sorokiniana, with an enhancement of 13.76%. To further evaluate the effects of Rhizobium sp. on microalgae under variations of temperature and sunlight intensity conditions, the open co-cultivation experiments were built outdoors. Results showed that the growth of C. sorokiniana could rise 13.29% only when Rhizobium sp. was added to the culture continuously, and addition of bacterial solution in log-phase of microalgae could help Rhizobium sp. dominate in the bacterial community. In this way, addition of Rhizobium sp. in the log-phase of C. sorokiniana should be an effective process to be applied to open ponds cultivation. Our findings are a step toward applying growth-promotion bacteria for C. sorokiniana for applications in open cultivation systems.