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1.
Mol Cell ; 65(2): 296-309, 2017 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-28065600

RESUMO

In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.


Assuntos
Aminoácido Oxirredutases/metabolismo , Linfócitos T CD4-Positivos/enzimologia , Colite/enzimologia , Processamento de Proteína Pós-Traducional , Fator de Transcrição STAT3/metabolismo , Acetilação , Aminoácido Oxirredutases/deficiência , Aminoácido Oxirredutases/genética , Animais , Linfócitos T CD4-Positivos/imunologia , Catálise , Diferenciação Celular , Núcleo Celular/enzimologia , Proliferação de Células , Colite/genética , Colite/imunologia , Modelos Animais de Doenças , Genótipo , Células HEK293 , Células HeLa , Humanos , Células MCF-7 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Domínios Proteicos , Multimerização Proteica , Interferência de RNA , Fator de Transcrição STAT3/genética , Linfócitos T Reguladores/enzimologia , Linfócitos T Reguladores/imunologia , Células Th17/enzimologia , Células Th17/imunologia , Transcrição Gênica , Transfecção
2.
J Biol Chem ; 299(2): 102911, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36642187

RESUMO

The attachment of a sugar to a hydrophobic lipid carrier is the first step in the biosynthesis of many glycoconjugates. In the halophilic archaeon Haloarcula hispanica, HAH_1206, renamed AepG, is a predicted glycosyltransferase belonging to the CAZy Group 2 family that shares a conserved amino acid sequence with dolichol phosphate mannose synthases. In this study, the function of AepG was investigated by genetic and biochemical approaches. We found that aepG deletion led to the disappearance of dolichol phosphate-glucuronic acid. Our biochemical assays revealed that recombinant cellulose-binding, domain-tagged AepG could catalyze the formation of dolichol phosphate-glucuronic acid in time- and dose-dependent manners. Based on the in vivo and in vitro analyses, AepG was confirmed to be a dolichol phosphate glucuronosyltransferase involved in the synthesis of the acidic exopolysaccharide produced by H. hispanica. Furthermore, lack of aepG resulted in hindered growth and cell aggregation in high salt medium, indicating that AepG is vital for the adaptation of H. hispanica to a high salt environment. In conclusion, AepG is the first dolichol phosphate glucuronosyltransferase identified in any of the three domains of life and, moreover, offers a starting point for further investigation into the diverse pathways used for extracellular polysaccharide biosynthesis in archaea.


Assuntos
Haloarcula , Sequência de Aminoácidos , Fosfatos de Dolicol/metabolismo , Haloarcula/metabolismo , Transferases/metabolismo , Polissacarídeos/metabolismo
3.
BMC Plant Biol ; 24(1): 290, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627629

RESUMO

BACKGROUND: Flesh firmness is a critical factor that influences fruit storability, shelf-life and consumer's preference as well. However, less is known about the key genetic factors that are associated with flesh firmness in fresh fruits like watermelon. RESULTS: In this study, through bulk segregant analysis (BSA-seq), we identified a quantitative trait locus (QTL) that influenced variations in flesh firmness among recombinant inbred lines (RIL) developed from cross between the Citrullus mucosospermus accession ZJU152 with hard-flesh and Citrullus lanatus accession ZJU163 with soft-flesh. Fine mapping and sequence variations analyses revealed that ethylene-responsive factor 1 (ClERF1) was the most likely candidate gene for watermelon flesh firmness. Furthermore, several variations existed in the promoter region between ClERF1 of two parents, and significantly higher expressions of ClERF1 were found in hard-flesh ZJU152 compared with soft-flesh ZJU163 at key developmental stages. DUAL-LUC and GUS assays suggested much stronger promoter activity in ZJU152 over ZJU163. In addition, the kompetitive allele-specific PCR (KASP) genotyping datasets of RIL populations and germplasm accessions further supported ClERF1 as a possible candidate gene for fruit flesh firmness variability and the hard-flesh genotype might only exist in wild species C. mucosospermus. Through yeast one-hybrid (Y1H) and dual luciferase assay, we found that ClERF1 could directly bind to the promoters of auxin-responsive protein (ClAux/IAA) and exostosin family protein (ClEXT) and positively regulated their expressions influencing fruit ripening and cell wall biosynthesis. CONCLUSIONS: Our results indicate that ClERF1 encoding an ethylene-responsive factor 1 is associated with flesh firmness in watermelon and provide mechanistic insight into the regulation of flesh firmness, and the ClERF1 gene is potentially applicable to the molecular improvement of fruit-flesh firmness by design breeding.


Assuntos
Citrullus , Citrullus/genética , Citrullus/metabolismo , Melhoramento Vegetal , Locos de Características Quantitativas/genética , Frutas/genética , Etilenos/metabolismo , Regiões Promotoras Genéticas/genética
4.
Small ; : e2407690, 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39344210

RESUMO

The strategic enhancement of manganese-oxygen (Mn─O) covalency is a promising approach to improve the intercalation kinetics of sodium ions (Na⁺) in manganese dioxide (MnO2). In this study, an augmenting Mn─O covalency in MnO2 by strategically incorporating cobalt at oxygen edge-sharing Co octahedral sites is focused on. Both experimental results and density functional theory (DFT) calculations reveal an increased electron polarization from oxygen to manganese, surpassing that directed toward cobalt, thereby facilitating enhanced electron transfer and strengthening covalency. The synthesized Co-MnO2 material exhibits outstanding electrochemical performance, demonstrating a superior specific capacitance of 388 F g-1 at 1 A g-1 and maintaining 97.21% capacity retention after 12000 cycles. Additionally, an asymmetric supercapacitor constructed using Co-MnO2 achieved a high energy density of 35 Wh kg-1 at a power density of 1000 W kg-1, underscoring the efficacy of this material in practical applications. This work highlights the critical role of transition metal-oxygen interactions in optimizing electrode materials and introduces a robust approach to enhance the functional properties of manganese oxides, thereby advancing high-performance energy storage technologies.

5.
Plant Biotechnol J ; 22(11): 3205-3217, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39229972

RESUMO

Eukaryotic translation initiation factors (eIFs) are the primary targets for overcoming RNA virus resistance in plants. In a previous study, we mapped a BjeIF2Bß from Brassica juncea representing a new class of plant virus resistance genes associated with resistance to Turnip mosaic virus (TuMV). However, the mechanism underlying eIF2Bß-mediated virus resistance remains unclear. In this study, we discovered that the natural variation of BjeIF2Bß in the allopolyploid B. juncea was inherited from one of its ancestors, B. rapa. By editing of eIF2Bß, we were able to confer resistance to TuMV in B. juncea and in its sister species of B. napus. Additionally, we identified an N6-methyladenosine (m6A) demethylation factor, BjALKBH9B, for interaction with BjeIF2Bß, where BjALKBH9B co-localized with both BjeIF2Bß and TuMV. Furthermore, BjeIF2Bß recruits BjALKBH9B to modify the m6A status of TuMV viral coat protein RNA, which lacks the ALKB homologue in its genomic RNA, thereby affecting viral infection. Our findings have applications for improving virus resistance in the Brassicaceae family through natural variation or genome editing of the eIF2Bß. Moreover, we uncovered a non-canonical translational control of viral mRNA in the host plant.


Assuntos
Resistência à Doença , Doenças das Plantas , Potyvirus , RNA Viral , RNA Viral/genética , RNA Viral/metabolismo , Doenças das Plantas/virologia , Doenças das Plantas/genética , Potyvirus/fisiologia , Resistência à Doença/genética , Metilação , Fator de Iniciação 2B em Eucariotos/genética , Fator de Iniciação 2B em Eucariotos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Enzimas AlkB/genética , Enzimas AlkB/metabolismo , Metilação de RNA
6.
Plant Biotechnol J ; 22(5): 1325-1334, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38213067

RESUMO

Cytoplasmic male sterility (CMS), encoded by the mitochondrial open reading frames (ORFs), has long been used to economically produce crop hybrids. However, the utilization of CMS also hinders the exploitation of sterility and fertility variation in the absence of a restorer line, which in turn narrows the genetic background and reduces biodiversity. Here, we used a mitochondrial targeted transcription activator-like effector nuclease (mitoTALENs) to knock out ORF138 from the Ogura CMS broccoli hybrid. The knockout was confirmed by the amplification and re-sequencing read mapping to the mitochondrial genome. As a result, knockout of ORF138 restored the fertility of the CMS hybrid, and simultaneously manifested a cold-sensitive male sterility. ORF138 depletion is stably inherited to the next generation, allowing for direct use in the breeding process. In addition, we proposed a highly reliable and cost-effective toolkit to accelerate the life cycle of fertile lines from CMS-derived broccoli hybrids. By applying the k-mean clustering and interaction network analysis, we identified the central gene networks involved in the fertility restoration and cold-sensitive male sterility. Our study enables mitochondrial genome editing via mitoTALENs in Brassicaceae vegetable crops and provides evidence that the sex production machinery and its temperature-responsive ability are regulated by the mitochondria.


Assuntos
Brassica , Infertilidade Masculina , Masculino , Humanos , Brassica/genética , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição , Melhoramento Vegetal , Mitocôndrias/genética , Fertilidade/genética , Infertilidade das Plantas/genética
7.
Plant Physiol ; 191(1): 369-381, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36179097

RESUMO

Cucumber green mottle mosaic virus (CGMMV) is one of the major global quarantine viruses and causes severe symptoms in Cucurbit crops, particularly with regard to fruit decay. However, the genetic mechanisms that control plant resistance to CGMMV have yet to be elucidated. Here, we found that WPRb, a weak chloroplast movement under blue light 1 and plastid movement impaired 2-related protein family gene, is recessively associated with CGMMV resistance in watermelon (Citrullus lanatus). We developed a reproducible marker based on a single non-synonymous substitution (G1282A) in WPRb, which can be used for marker-assisted selection for CGMMV resistance in watermelon. Editing of WPRb conferred greater tolerance to CGMMV. We found WPRb targets to the plasmodesmata (PD) and biochemically interacts with the CGMMV movement protein, facilitating viral intercellular movement by affecting the permeability of PD. Our findings enable us to genetically control CGMMV resistance in planta by using precise genome editing techniques targeted to WPRb.


Assuntos
Citrullus , Tobamovirus , Tobamovirus/genética , Citrullus/genética , Doenças das Plantas/genética
8.
Plant Physiol ; 193(2): 1330-1348, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37477947

RESUMO

Sweetness and appearance of fresh fruits are key palatable and preference attributes for consumers and are often controlled by multiple genes. However, fine-mapping the key loci or genes of interest by single genome-based genetic analysis is challenging. Herein, we present the chromosome-level genome assembly of 1 landrace melon accession (Cucumis melo ssp. agrestis) with wild morphologic features and thus construct a melon pan-genome atlas via integrating sequenced melon genome datasets. Our comparative genomic analysis reveals a total of 3.4 million genetic variations, of which the presence/absence variations (PAVs) are mainly involved in regulating the function of genes for sucrose metabolism during melon domestication and improvement. We further resolved several loci that are accountable for sucrose contents, flesh color, rind stripe, and suture using a structural variation (SV)-based genome-wide association study. Furthermore, via bulked segregation analysis (BSA)-seq and map-based cloning, we uncovered that a single gene, (CmPIRL6), determines the edible or inedible characteristics of melon fruit exocarp. These findings provide important melon pan-genome information and provide a powerful toolkit for future pan-genome-informed cultivar breeding of melon.


Assuntos
Cucumis melo , Cucurbitaceae , Mapeamento Cromossômico , Cucurbitaceae/genética , Cucurbitaceae/metabolismo , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Genes de Plantas , Cucumis melo/genética , Frutas/genética , Frutas/metabolismo
9.
Theor Appl Genet ; 137(5): 98, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592431

RESUMO

KEY MESSAGE: The ClLOG gene encoding a cytokinin riboside 5'-monophosphate phosphoribohydrolase determines trichome length in watermelon, which is associated with its promoter variations. Trichomes, which are differentiated from epidermal cells, are special accessory structures that cover the above-ground organs of plants and possibly contribute to biotic and abiotic stress resistance. Here, a bulked segregant analysis (BSA) of an F2 population with significant variations in trichome length was undertaken. A 1.84-Mb candidate region on chromosome 10 was associated with trichome length. Resequencing and fine-mapping analyses indicated that a 12-kb structural variation in the promoter of Cla97C10G203450 (ClLOG) led to a significant expression difference in this gene in watermelon lines with different trichome lengths. In addition, a virus-induced gene silencing analysis confirmed that ClLOG positively regulated trichome elongation. These findings provide new information and identify a potential target gene for controlling multicellular trichome elongation in watermelon.


Assuntos
Citocininas , Tricomas , Tricomas/genética , Glicosídeos , Regiões Promotoras Genéticas , Análise de Sequência de DNA
10.
Pharmacol Res ; 203: 107149, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518830

RESUMO

Neuronal health is closely linked to the homeostasis of intracellular organelles, and organelle dysfunction affects the pathological progression of neurological diseases. In contrast to isolated cellular compartments, a growing number of studies have found that organelles are largely interdependent structures capable of communicating through membrane contact sites (MCSs). MCSs have been identified as key pathways mediating inter-organelle communication crosstalk in neurons, and their alterations have been linked to neurological disease pathology. The endoplasmic reticulum (ER) is a membrane-bound organelle capable of forming an extensive network of pools and tubules with important physiological functions within neurons. There are multiple MCSs between the ER and other organelles and the plasma membrane (PM), which regulate a variety of cellular processes. In this review, we focus on ER-organelle MCSs and their role in a variety of neurological diseases. We compared the biological effects between different tethering proteins and the effects of their respective disease counterparts. We also discuss how altered ER-organelle contacts may affect disease pathogenesis. Therefore, understanding the molecular mechanisms of ER-organelle MCSs in neuronal homeostasis will lay the foundation for the development of new therapies targeting ER-organelle contacts.


Assuntos
Retículo Endoplasmático , Doenças do Sistema Nervoso , Transdução de Sinais , Humanos , Retículo Endoplasmático/metabolismo , Animais , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/patologia , Neurônios/metabolismo , Organelas/metabolismo
11.
Physiol Plant ; 176(5): e14553, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39377147

RESUMO

Trichomes are specialized structures derived from epidermal cells. Non-glandular trichomes primarily protect plants from herbivores and intense ultraviolet radiation by acting as a physical barrier. Recent research has highlighted the importance of homeodomain leucine zipper (HD-Zip) IV transcription factors (TFs) in promoting trichome development. In this study, an HD-Zip III TF called PHAVOLUTA (BjPHVa) was identified as a negative regulator of non-glandular trichome initiation in Brassica juncea. Genome editing of BjPHVa resulted in a significant increase in trichome number in B. juncea. Co-expression networks revealed a strong association between trichome development and the HD-Zip family, which was supported by transcriptomic analysis findings. An R2R3-MYB TF, BjGL1a, a key regulator of trichome development, was found to be associated with BjPHVa-regulated trichome development. Knockdown of BjGL1a expression resulted in reduced trichome number in B. juncea. BjPHVa was observed to interact directly with BjGL1a while binding to the BjGL1a promoter, resulting in the inhibition of BjGL1a transcription. These results provide new insights into the identification of regulators involved in trichome development and offer new opportunities to enhance resistance to predicted stresses through genome editing targeting PHVa within Brassicaceae.


Assuntos
Regulação da Expressão Gênica de Plantas , Mostardeira , Proteínas de Plantas , Fatores de Transcrição , Tricomas , Tricomas/genética , Tricomas/crescimento & desenvolvimento , Tricomas/metabolismo , Mostardeira/genética , Mostardeira/crescimento & desenvolvimento , Mostardeira/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo
12.
Brain ; 146(8): 3373-3391, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36825461

RESUMO

GGC repeat expansion in the 5' untranslated region (UTR) of NOTCH2NLC is associated with a broad spectrum of neurological disorders, especially neuronal intranuclear inclusion disease (NIID). Studies have found that GGC repeat expansion in NOTCH2NLC induces the formation of polyglycine (polyG)-containing protein, which is involved in the formation of neuronal intranuclear inclusions. However, the mechanism of neurotoxicity induced by NOTCH2NLC GGC repeats is unclear. Here, we used NIID patient-specific induced pluripotent stem cell (iPSC)-derived 3D cerebral organoids (3DCOs) and cellular models to investigate the pathophysiological mechanisms of NOTCH2NLC GGC repeat expansion. IPSC-derived 3DCOs and cellular models showed the deposition of polyG-containing intranuclear inclusions. The NOTCH2NLC GGC repeats could induce the upregulation of autophagic flux, enhance integrated stress response and activate EIF2α phosphorylation. Bulk RNA sequencing for iPSC-derived neurons and single-cell RNA sequencing (scRNA-seq) for iPSC-derived 3DCOs revealed that NOTCH2NLC GGC repeats may be associated with dysfunctions in ribosome biogenesis and translation. Moreover, NOTCH2NLC GGC repeats could induce the NPM1 nucleoplasm translocation, increase nucleolar stress, impair ribosome biogenesis and induce ribosomal RNA sequestration, suggesting dysfunction of membraneless organelles in the NIID cellular model. Dysfunctions in ribosome biogenesis and phosphorylated EIF2α and the resulting increase in the formation of G3BP1-positive stress granules may together lead to whole-cell translational inhibition, which may eventually cause cell death. Interestingly, scRNA-seq revealed that NOTCH2NLC GGC repeats may be associated with a significantly decreased proportion of immature neurons while 3DCOs were developing. Together, our results underscore the value of patient-specific iPSC-derived 3DCOs in investigating the mechanisms of polyG diseases, especially those caused by repeats in human-specific genes.


Assuntos
DNA Helicases , RNA Helicases , Humanos , Proteínas de Ligação a Poli-ADP-Ribose , Proteínas com Motivo de Reconhecimento de RNA , Regiões 5' não Traduzidas , Corpos de Inclusão Intranuclear , Ribossomos , Expansão das Repetições de Trinucleotídeos/genética
13.
Ergonomics ; 67(4): 515-525, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37365918

RESUMO

To investigate whether high cognitive task load (CTL) for aircraft pilots can be identified by analysing heart-rate variability, electrocardiograms were recorded while cadet pilots (n = 68) performed the plane tracking, anti-gravity pedalling, and reaction tasks during simulated flight missions. Data for standard electrocardiogram parameters were extracted from the R-R-interval series. In the research phase, low frequency power (LF), high frequency power (HF), normalised HF, and LF/HF differed significantly between high and low CTL conditions (p < .05 for all). A principal component analysis identified three components contributing 90.62% of cumulative heart-rate variance. These principal components were incorporated into a composite index. Validation in a separate group of cadet pilots (n = 139) under similar conditions showed that the index value significantly increased with increasing CTL (p < .05). The heart-rate variability index can be used to objectively identify high CTL flight conditions.Practitioner summary: We used principal component analysis of electrocardiogram data to construct a composite index for identifying high cognitive task load in pilots during simulated flight. We validated the index in a separate group of pilots under similar conditions. The index can be used to improve cadet training and flight safety.Abbreviations: ANOVA: a one-way analysis of variance; AP: anti-gravity pedaling task; CTL: cognitive task load; ECG: electrocardiograms; HR: heart rate; HRV: heart-rate variability; HRVI: heart-rate variability index; PT: plane-tracking task; RMSSD: root-mean square of differences between consecutive R-R intervals; RT: reaction task; SDNN: standard deviation of R-R intervals; HF: high frequency power; HFnu: normalized HF; LF: low frequency power; LFnu: normalized LF; PCA: principal component analysis.


Assuntos
Cognição , Eletrocardiografia , Humanos , Frequência Cardíaca/fisiologia , Análise de Componente Principal
14.
Angew Chem Int Ed Engl ; : e202415997, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39305188

RESUMO

The pressing demand for large-scale energy storage solutions has propelled the development of advanced battery technologies, among which zinc-ion batteries (ZIBs) are prominent due to their resource abundance, high capacity, and safety in aqueous environments. However, the use of manganese oxide cathodes in ZIBs is challenged by their poor electrical conductivity and structural stability, stemming from the intrinsic properties of MnO2 and the destabilizing effects of ion intercalation. To overcome these limitations, our research delves into atomic-level engineering, emphasizing quantum spin exchange interactions (QSEI). These essential for modifying electronic characteristics, can significantly influence material efficiency and functionality. We demonstrate through density functional theory (DFT) calculations that enhanced QSEI in manganese oxides broadens the O p band, narrows the band gap, and optimizes both proton adsorption and electron transport. Empirical evidence is provided through the synthesis of Ru-MnO2 nanosheets, which display a marked increase in energy storage capacity, achieving 314.4 mAh g-1 at 0.2 A g-1 and maintaining high capacity after 2000 cycles. Our findings underscore the potential of QSEI to enhance the performance of TMO cathodes in ZIBs, pointing to new avenues for advancing battery technology.

15.
Angew Chem Int Ed Engl ; 63(35): e202408414, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-38850273

RESUMO

Transition metal oxides (TMOs) are promising cathode materials for aqueous zinc ion batteries (ZIBs), however, their performance is hindered by a substantial Hubbard gap, which limits electron transfer and battery cyclability. Addressing this, we introduce a heteroatom coordination approach, using triethanolamine to induce axial N coordination on Mn centers in MnO2, yielding N-coordinated MnO2 (TEAMO). This approach leverages the change of electronegativity disparity between Mn and ligands (O and N) to disrupt spin symmetry and augment spin polarization. This enhancement leads to the closure of the Hubbard gap, primarily driven by the intensified occupancy of the Mn eg orbitals. The resultant TEAMO exhibit a significant increase in storage capacity, reaching 351 mAh g-1 at 0.1 A g-1. Our findings suggest a viable strategy for optimizing the electronic structure of TMO cathodes, enhancing the potential of ZIBs in energy storage technology.

16.
Cell Mol Neurobiol ; 43(3): 1181-1196, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35661286

RESUMO

Lanthanum (La) is a natural rare-earth element that can damage the central nervous system and impair learning and memory. However, its neurotoxic mechanism remains unclear. In this study, adult female rats were divided into 4 groups and given distilled water solution containing 0%, 0.125%, 0.25%, and 0.5% LaCl3, respectively, and this was done from conception to the end of the location. Their offspring rats were used to establish animal models to investigate LaCl3 neurotoxicity. Primary neurons cultured in vitro were treated with LaCl3 and infected with LKB1 overexpression lentivirus. The results showed that LaCl3 exposure resulted in abnormal axons in the hippocampus and primary cultured neurons. LaCl3 reduced the expression of LKB1, p-LKB1, STRAD and MO25 proteins, and directly or indirectly affected the expression of LKB1, leading to decreased activity of LKB1-MARK2 and LKB1-STK25-GM130 pathways. This study indicated that LaCl3 exposure could interfere with the normal effects of LKB1 in the brain and downregulate LKB1-MARK2 and LKB1-STK25-GM130 signaling pathways, resulting in abnormal axon in offspring rats.


Assuntos
Axônios , Lantânio , Ratos , Feminino , Animais , Lantânio/toxicidade , Ratos Wistar , Transdução de Sinais , Proteínas Serina-Treonina Quinases
17.
Theor Appl Genet ; 136(4): 75, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36952042

RESUMO

KEY MESSAGE: A 448 kb region on chromosome B02 was delimited to be associated with trichome trait in Brassica juncea, in which the BjuVB02G54610 gene with a structural variation of 3 kb structure variation (SV) encoding a MYB transcription factor was predicted as the possible candidate gene. Mustards (Brassica juncea) are allopolyploid crops in the worldwide, and trichomes are essential quality attributes that significantly influence its taste and palpability in vegetable-use cultivars. As important accessory tissues from specialized epidermal cells, trichomes also play an important role in mitigating biotic and abiotic stresses. In this study, we constructed a F2 segregating population using YJ27 with intensive trichome leaves and 03B0307 with glabrous leaves as parents. By bulked segregant analysis (BSA-seq), we obtained a 2.1 Mb candidate region on B02 chromosome associated with the trichome or glabrous trait formation. Then, we used 13 Kompetitive Allele Specific PCR (KASP) markers for fine mapping and finally narrowed down the candidate region to about 448 kb in length. Interestingly, among the region, there was a 3 kb sequence deletion that located on the BjuVB02G54610 gene in the F2 individuals with trichome leaves. Genotyping results of F2 populations confirmed this deletion (R2 = 81.44%) as a major QTL. Natural population re-sequencing analysis and genotyping results further validated the key role of the 3 kb structure variation (SV) of insertion/deletion type in trichome development in B. juncea. Our findings provide important information on the formation of trichomes and potential target gene for breeding vegetable mustards.


Assuntos
Mostardeira , Tricomas , Humanos , Mostardeira/genética , Tricomas/genética , Melhoramento Vegetal , Fenótipo , Fatores de Transcrição/genética , Verduras
18.
Theor Appl Genet ; 136(9): 199, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37624448

RESUMO

KEY MESSAGE: The ClACO gene encoding 1-aminocyclopropane-1-carboxylate oxidase enabled highly efficient 15N uptake in watermelon. Nitrogen is one of the most essential nutrient elements that play a pivotal role in regulating plant growth and development for crop productivity. Elucidating the genetic basis of high nitrogen uptake is the key to improve nitrogen use efficiency for sustainable agricultural productivity. Whereas previous researches on nitrogen absorption process are mainly focused on a few model plants or crops. To date, the causal genes that determine the efficient nitrogen uptake of watermelon have not been mapped and remains largely unknown. Here, we fine-mapped the 1-aminocyclopropane-1-carboxylate oxidase (ClACO) gene associated with nitrogen uptake efficiency in watermelon via bulked segregant analysis (BSA). The variations in the ClACO gene led to the changes of gene expression levels between two watermelon accessions with different nitrogen uptake efficiencies. Intriguingly, in terms of the transcript abundance of ClACO, it was concomitant with significant differences in ethylene evolutions in roots and root architectures between the two accessions and among the different genotypic offsprings of the recombinant BC2F1(ZJU132)-18. These findings suggest that ethylene as a negative regulator altered nitrogen uptake efficiency in watermelon by controlling root development. In conclusion, our current study will provide valuable target gene for precise breeding of 'green' watermelon varieties with high-nitrogen uptake efficiencies.


Assuntos
Etilenos , Melhoramento Vegetal , Alelos , Nitrogênio
19.
J Biochem Mol Toxicol ; 37(11): e23451, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37393519

RESUMO

Sanguinarine is an alkaloid with diverse biological activities, nevertheless, whether it can target epigenetic modifiers remains unknown. In this study, sanguinarine was characterized as a strong BRD4 inhibitor with IC50 = 361.3 nM against BRD4 (BD1) and IC50 = 302.7 nM against BRD4 (BD2) that can inactivate BRD4 reversibly. Additional cellular assays suggested that sanguinarine can bind BRD4 in human clear cell renal cell carcinoma (ccRCC) cell line 786-O and inhibit cell growth with IC50 (24 h) = 0.6752 µM and IC50 (48 h) = 0.5959 µM in a BRD4 dependent manner partially. Meanwhile, sanguinarine can inhibit the migration of 786-O cells in vitro and in vivo, and reverse epithelial-mesenchymal transition. Moreover, it can inhibit 786-O cells proliferation in vivo in a BRD4 dependent manner partially. In sum, our study identified BRD4 as a new target of sanguinarine, and sanguinarine may serve as a potential therapeutic agent against ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Proliferação de Células , Neoplasias Renais/tratamento farmacológico , Linhagem Celular Tumoral , Proteínas de Ciclo Celular
20.
J Nerv Ment Dis ; 211(1): 23-28, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35926188

RESUMO

ABSTRACT: Sleep disorders persist in renal transplant patients. Previous studies have showed that fatigue and rumination are an important determinant of sleep quality. However, very few studies have explored the mediating role of rumination in the relationship between fatigue and sleep quality in kidney transplant recipients. A descriptive cross-sectional research design was implemented, and 192 kidney transplant patients completed the short questionnaire about their recent experiences of fatigue, rumination, and sleep quality. The prevalence of sleep disorders among kidney transplant recipients was 19.3%. With rumination as a partial mediator, fatigue indirectly affected the patients' sleep quality. This indirect effect was 0.10 (95% confidence interval, 0.154-0.419). Our results indicate that the incidence of sleep disorders after renal transplantation was high, and the more tired kidney transplant recipients become, the more likely they are to ruminate, which leads to a decline in sleep quality.


Assuntos
Transplante de Rim , Transtornos do Sono-Vigília , Humanos , Qualidade do Sono , Transplante de Rim/efeitos adversos , Estudos Transversais , Inquéritos e Questionários , Fadiga/epidemiologia , Fadiga/etiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Sono
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