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1.
Biotechnol J ; 19(3): e2300579, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494424

RESUMO

Fluorescent initiator tRNAs (tRNAi) play a crucial role in studying protein synthesis, yet generating highly fluorescent tRNAi complexes remains challenging. We present an optimized strategy to effectively generate highly fluorescent initiator-tRNA complexes in living cells. Our strategy allows the generation of Fluo-Met-tRNAiMet complexes. These complexes can have highly chromogenic N-terminal labeling. For generating such complexes, we use either purified fluorescent methionine (PFM) or non-purified fluorescently labeled methionine (NPFM). Furthermore, PFM promotes the active generation of endogenous tRNAi in cells, leading to highly efficient Fluo-Met-tRNAiMet complexes. Finally, PFM-tRNAiMet complexes also facilitate the visualization of native fluorescently labeled Tat binding to beads. This demonstrates the potential of our approach to advance precision protein engineering and biotechnology applications.


Assuntos
Biossíntese de Proteínas , RNA de Transferência de Metionina , RNA de Transferência de Metionina/química , RNA de Transferência de Metionina/genética , RNA de Transferência de Metionina/metabolismo , Metionina/genética , Metionina/metabolismo , Corantes , Racemetionina/metabolismo
2.
Food Microbiol ; 120: 104467, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38431319

RESUMO

The luxS mutant strains of Shewanella putrefaciens (SHP) were constructed to investigate the regulations of gene luxS in spoilage ability. The potential regulations of AI-2 quorum sensing (QS) system and activated methyl cycle (AMC) were studied by analyzing the supplementation roles of key circulating substances mediated via luxS, including S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), methionine (Met), homocysteine (Hcy) and 4,5-dihydroxy-2,3-pentanedione (DPD). Growth experiments revealed that the luxS deletion led to certain growth limitations of SHP, which were associated with culture medium and exogenous additives. Meanwhile, the decreased biofilm formation and diminished hydrogen sulfide (H2S) production capacity of SHP were observed after luxS deletion. The relatively lower total volatile base nitrogen (TVB-N) contents and higher sensory scores of fish homogenate with luxS mutant strain inoculation also indicated the weaker spoilage-inducing effects after luxS deletion. However, these deficiencies could be offset with the exogenous supply of circulating substances mentioned above. Our findings suggested that the luxS deletion would reduce the spoilage ability of SHP, which was potentially attributed to the disorder of AMC and AI-2 QS system.


Assuntos
Percepção de Quorum , Shewanella putrefaciens , Animais , Percepção de Quorum/genética , Shewanella putrefaciens/genética , Shewanella putrefaciens/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Metionina/genética , Metionina/metabolismo , Biofilmes , Regulação Bacteriana da Expressão Gênica
3.
Mol Genet Genomics ; 299(1): 7, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349549

RESUMO

Traditional maize grain is deficient in methionine, an essential amino acid required for proper growth and development in humans and poultry birds. Thus, development of high methionine maize (HMM) assumes great significance in alleviating malnutrition through sustainable and cost-effective approach. Of various genetic loci, aspartate kinase2 (ask2) gene plays a pivotal role in regulating methionine accumulation in maize. Here, we sequenced the entire ask2 gene of 5394 bp with 13 exons in five wild and five mutant maize inbreds to understand variation at nucleotide level. Sequence analysis revealed that an SNP in exon-13 caused thymine to adenine transversion giving rise to a favourable mutant allele associated with leucine to glutamine substitution in mutant ASK2 protein. Gene-based diversity analysis with 11 InDel markers grouped 48 diverse inbreds into three major clusters with an average genetic dissimilarity of 0.570 (range, 0.0-0.9). The average major allele frequency, gene diversity and PIC are 0.693, 0.408 and 0.341, respectively. A total of 45 haplotypes of the ask2 gene were identified among the maize inbreds. Evolutionary relationship analysis performed among 22 orthologues grouped them into five major clusters. The number of exons varied from 7 to 17, with length varying from 12 to 495 bp among orthologues. ASK2 protein with 565 amino acids was predicted to be in homo-dimeric state with lysine and tartaric acid as binding ligands. Amino acid kinase and ACT domains were found to be conserved in maize and orthologues. The study depicted the presence of enough genetic diversity in ask2 gene in maize, and development of HMM can be accelerated through introgression of favourable allele of ask2 into the parental lines of elite hybrids using molecular breeding.


Assuntos
Ácido Aspártico , Zea mays , Aminoácidos , Haplótipos , Metionina/genética , Racemetionina , Zea mays/genética
4.
BMJ Case Rep ; 17(2)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388201

RESUMO

Variably protease-sensitive prionopathy (VPSPr) is a recently characterised rare subtype of sporadic prion disease, mainly affecting individuals with valine homozygosity at codon 129 in the prion protein gene, with only seven methionine homozygote cases reported to date. This case presents clinical, neuropathological and biochemical features of the eighth VPSPr case worldwide with methionine homozygosity at codon 129 and compares the features with the formerly presented cases.The patient, a woman in her 70s, presented with cognitive decline, impaired balance and frequent falls. Medical history and clinical presentation were suggestive of a rapidly progressive dementia disorder. MRI showed bilateral thalamic hyperintensity. Cerebrospinal fluid real-time quaking-induced conversion was negative, and the electroencephalogram was unremarkable. The diagnosis was established through post-mortem pathological examinations. VPSPr should be suspected in rapidly progressive dementia lacking typical features or paraclinical results of protein misfolding diseases.


Assuntos
Síndrome de Creutzfeldt-Jakob , Demência , Doenças Priônicas , Príons , Feminino , Humanos , Príons/genética , Príons/metabolismo , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Metionina/genética , Metionina/metabolismo , Homozigoto , Encéfalo/patologia , Doenças Priônicas/genética , Doenças Priônicas/metabolismo , Doenças Priônicas/patologia , Demência/genética , Racemetionina/metabolismo , Códon/genética , Códon/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Síndrome de Creutzfeldt-Jakob/patologia
5.
J Neurooncol ; 166(1): 195-201, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38160415

RESUMO

PURPOSE: Distinguishing between primary central nervous system lymphoma (PCNSL) and isocitrate dehydrogenase (IDH)-wildtype glioblastoma is important for therapeutic decision-making. This study aimed to compare the performance of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing between these two major malignant brain tumors. METHODS: We retrospectively conducted qualitative and semiquantitative analyses of pre-treatment MET and FDG PET/computed tomography (CT) images of 22 patients with PCNSL and 64 patients with IDH-wildtype glioblastoma. For semiquantitative analysis, we calculated the tumor-to-normal tissue (T/N) ratio by dividing the maximum standardized uptake value (SUV) for the tumor (T) by the average SUV for the normal tissue (N). For performance evaluation, we employed receiver operating characteristic curve analysis and calculated the areas under the curve (AUC) values. RESULTS: In the qualitative analysis, all PCNSLs and IDH-wildtype glioblastomas were MET-positive, while 95% and 84% of PCNSLs and IDH-wildtype glioblastomas, respectively, were FDG-positive. Eleven patients were excluded from the FDG PET/CT semiquantitative analysis because of hyperglycemia. There was no difference in MET T/N ratio between PCNSL and IDH-wildtype glioblastoma (p = 0.37). FDG T/N ratio was significantly higher in PCNSL than in IDH-wildtype glioblastoma (p < 0.001). The AUC value for distinguishing PCNSL from IDH-wildtype glioblastoma was significantly higher for the FDG T/N ratio (0.871) than for the MET T/N ratio (0.565) (p = 0.0027). CONCLUSION: MET PET could detect both PCNSL and IDH-wildtype glioblastoma, but unlike FDG PET, it could not distinguish between these two major malignant brain tumors.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Linfoma , Humanos , Fluordesoxiglucose F18 , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioblastoma/patologia , Metionina/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Isocitrato Desidrogenase/genética , Estudos Retrospectivos , Linfoma/diagnóstico por imagem , Linfoma/genética , Linfoma/patologia , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Racemetionina , Sistema Nervoso Central/patologia , Compostos Radiofarmacêuticos
6.
Development ; 150(21)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37846748

RESUMO

Histone modifications are associated with regulation of gene expression that controls a vast array of biological processes. Often, these associations are drawn by correlating the genomic location of a particular histone modification with gene expression or phenotype; however, establishing a causal relationship between histone marks and biological processes remains challenging. Consequently, there is a strong need for experimental approaches to directly manipulate histone modifications. A class of mutations on the N-terminal tail of histone H3, lysine-to-methionine (K-to-M) mutations, was identified as dominant-negative inhibitors of histone methylation at their respective and specific residues. The dominant-negative nature of K-to-M mutants makes them a valuable tool for studying the function of specific methylation marks on histone H3. Here, we review recent applications of K-to-M mutations to understand the role of histone methylation during development and homeostasis. We highlight important advantages and limitations that require consideration when using K-to-M mutants, particularly in a developmental context.


Assuntos
Cromatina , Histonas , Histonas/metabolismo , Cromatina/genética , Metilação , Mutação/genética , Metionina/genética , Metionina/metabolismo
7.
PLoS Genet ; 19(9): e1010927, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37733784

RESUMO

The emergence of fungicide resistance severely threatens crop production by limiting the availability and application of established fungicides. Therefore, it is urgent to identify new fungicidal targets for controlling plant diseases. Here, we characterized the function of a conserved homoserine O-acetyltransferase (HOA) from the rice blast fungus Magnaporthe oryzae that could serve as the candidate antifungal target. Deletion of the MoMET2 and MoCYS2 genes encoding HOAs perturbed the biosynthesis of methionine and S-adenyl methionine, a methyl group donor for epigenetic modifications, and severely attenuated the development and virulence of M. oryzae. The ∆Momet2 mutant is significantly increased in 5-methylcytosine (5mC) modification that represses the expression of genes required for pathogenicity, including MoGLIK and MoCDH-CYT. We further showed that host-induced gene silencing (HIGS) targeting MoMET2 and MoCYS2 effectively controls rice blasts. Our studies revealed the importance of HOA in the development and virulence of M. oryzae, which suggests the potential feasibility of HOA as new targets for novel anti-rice blast measurements.


Assuntos
Magnaporthe , Oryza , Virulência/genética , Oryza/metabolismo , Metionina/genética , Expressão Gênica , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
8.
PLoS One ; 18(9): e0291397, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37703265

RESUMO

The protein brain-derived neurotrophic factor (BDNF) promotes neural plasticity of the central nervous system and plays an important role for learning and memory. A single nucleotide polymorphism (rs6265) at position 66 in the pro-region of the human BDNF gene, resulting in a substitution of the amino acid valine (val) with methionine (met), leads to attenuated BDNF secretion and has been associated with reduced neurocognitive function. Inhomogeneous results have been found regarding the effect of the BDNF genotype on behavior. We determined the BDNF genotype and performance on the Compound Remote Associate (CRA) task as a common measure of creativity in 76 healthy university students. In our main analyses, we did not find significant differences between met-carriers (n = 30) and non-met carriers (n = 46). In a secondary analysis, we found that met-carriers had a slower solution time (medium effect size) for items of medium difficulty. Our results suggest that met-carriers and non-met-carriers do not generally differ regarding their creativity, but non-met-carriers may have a certain advantage when it comes to moderately difficult problems. The wider literature suggests that both genetic variants come with advantages and disadvantages. Future research needs to sharpen our understanding of the disadvantages and, potentially, advantages met allele carriers may have.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Metionina , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Genótipo , Metionina/genética , Polimorfismo de Nucleotídeo Único , Racemetionina
9.
Plant Cell Rep ; 42(11): 1721-1732, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37594528

RESUMO

KEY MESSAGE: Ethylene formation via methionine reacting with trichloroisocyanuric acid under FeSO4 condition in a non-enzymatical manner provides one economically and efficiently novel ethylene-forming approach in planta. Rice seed germination can be stimulated by trichloroisocyanuric acid (TCICA). However, the molecular basis of TCICA in stimulating rice seed germination remains unclear. In this study, the molecular mechanism on how TCICA stimulated rice seed germination was examined via comparative transcriptome. Results showed that clustering of transcripts of TCICA-treated seeds, water-treated seeds, and dry seeds was clearly separated. Twenty-two and three hundred differentially expressed genes were identified as TCICA treatment responsive genes and TCICA treatment potentially responsive genes, respectively. Two and one TCICA treatment responsive genes were involved in ethylene signal transduction and iron homeostasis, respectively. Seventeen of the three hundred TCICA treatment potentially responsive genes were significantly annotated to iron ion binding. Meanwhile, level of methionine (ethylene precursor) showed a 73.9% decrease in response to TCICA treatment. Ethylene was then proved to produce via methionine reacting with TCICA under FeSO4 condition in vitro. Revealing ethylene formation by TCICA not only may bring novel insights into crosstalk between ethylene and other phytohormones during rice seed germination, but also may provide one economically and efficiently novel approach to producing ethylene in planta independently of the ethylene biosynthesis in plants and thereby may broaden its applications in investigational and applied purposes.


Assuntos
Oryza , Oryza/genética , Oryza/metabolismo , Germinação/genética , Perfilação da Expressão Gênica , Etilenos/farmacologia , Etilenos/metabolismo , Sementes/metabolismo , Transcriptoma/genética , Metionina/genética , Metionina/metabolismo , Ferro/metabolismo , Regulação da Expressão Gênica de Plantas , Ácido Abscísico/metabolismo
10.
EMBO J ; 42(17): e114879, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37519235

RESUMO

The natural variation in mammalian longevity and its underlying mechanisms remain an active area of aging research. In the latest issue of The EMBO Journal, Liu et al (2023) analyze gene expression levels in 103 mammalian species across three tissues, revealing tissue-specific associations between gene expression patterns and longevity. Remarkably, the study suggests that methionine restriction, a strategy shown to increase lifespan, may extend beyond artificial interventions and is similarly employed by natural selection.


Assuntos
Longevidade , Metionina , Animais , Longevidade/genética , Metionina/genética , Metionina/metabolismo , Mamíferos/genética , Expressão Gênica , Envelhecimento/genética , Envelhecimento/metabolismo
11.
Cancer Cell ; 41(6): 1118-1133.e12, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37267951

RESUMO

Cyclic GMP-AMP synthase (cGAS) is the major sensor for cytosolic DNA and activates type I interferon signaling and plays an essential role in antitumor immunity. However, it remains unclear whether the cGAS-mediated antitumor activity is affected by nutrient status. Here, our study reports that methionine deprivation enhances cGAS activity by blocking its methylation, which is catalyzed by methyltransferase SUV39H1. We further show that methylation enhances the chromatin sequestration of cGAS in a UHRF1-dependent manner. Blocking cGAS methylation enhances cGAS-mediated antitumor immunity and suppresses colorectal tumorigenesis. Clinically, cGAS methylation in human cancers correlates with poor prognosis. Thus, our results indicate that nutrient stress promotes cGAS activation via reversible methylation, and suggest a potential therapeutic strategy for targeting cGAS methylation in cancer treatment.


Assuntos
Cromatina , Metionina , Humanos , Cromatina/genética , Metionina/genética , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , DNA , Imunidade Inata , Desmetilação , Proteínas Estimuladoras de Ligação a CCAAT/genética , Ubiquitina-Proteína Ligases/genética
13.
Pain Res Manag ; 2023: 7313578, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37305098

RESUMO

Fibromyalgia (FM) is a disorder characterized by chronic musculoskeletal pain, fatigue, and cognitive problems. Neurotransmitters, mainly catecholamines, appear to be involved in regulating the etiology of FM. Catechol-O-methyltransferase (COMT) is involved in catabolizing catecholamines such as norepinephrine. The most common variant studied in the COMT gene is the valine (Val) to methionine (Met) substitution at codon 158. This is the first study in Sudan addressing FM cases and genetic susceptibility to the disease. We aimed in this study to investigate the frequency of COMT Val 158 Met polymorphism among patients with FM, rheumatoid arthritis, and in healthy individuals. Genomic DNA from forty female volunteers was analyzed: twenty were from primary and secondary FM patients, ten were from rheumatoid arthritis patients, and ten were from healthy control. FM patients' age was ranging from 25 years to 55 with a mean of 41.14 ± 8.90. The mean age of the rheumatoid arthritis patients and healthy individuals was 31.3 ± 7.5 and 38.6 ± 11.2, respectively. Samples were genotyped for COMT single nucleotide polymorphism rs4680 (Val158Met), using the amplification-refractory mutation system (ARMS-PCR). Genotyping data have been analyzed using the Chi-square and Fisher exact test. The most common genotype among the study participants was the heterozygous Val/Met found in all participants. It was the only genotype found in the healthy participants. The genotype Met/Met was found only in FM patients. The genotype Val/Val was found only in rheumatoid patients. Analyses have shown no association between the Met/Met genotype and FM, and this could be due to a small sample size. In a larger sample size, a significant association could be found as this genotype was shown only by FM patients. Moreover, the Val/Val genotype, which is shown only among rheumatoid patients, might protect them from developing FM symptoms.


Assuntos
Artrite Reumatoide , Fibromialgia , Adulto , Feminino , Humanos , Catecol O-Metiltransferase/genética , Catecolaminas , Fibromialgia/genética , Metionina/genética , Racemetionina , Sudão , Pessoa de Meia-Idade
14.
Cell Oncol (Dordr) ; 46(6): 1659-1673, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37318751

RESUMO

BACKGROUND: Recent studies have uncovered the near-ubiquitous presence of microbes in solid tumors of diverse origins. Previous literature has shown the impact of specific bacterial species on the progression of cancer. We propose that local microbial dysbiosis enables certain cancer phenotypes through provisioning of essential metabolites directly to tumor cells. METHODS: 16S rDNA sequencing of 75 patient lung samples revealed the lung tumor microbiome specifically enriched for bacteria capable of producing methionine. Wild-type (WT) and methionine auxotrophic (metA mutant) E. coli cells were used to condition cell culture media and the proliferation of lung adenocarcinoma (LUAD) cells were measured using SYTO60 staining. Further, colony forming assay, Annexin V Staining, BrdU, AlamarBlue, western blot, qPCR, LINE microarray and subcutaneous injection with methionine modulated feed were used to analyze cellular proliferation, cell-cycle, cell death, methylation potential, and xenograft formation under methionine restriction. Moreover, C14-labeled glucose was used to illustrate the interplay between tumor cells and bacteria. RESULTS/DISCUSSION: Our results show bacteria found locally within the tumor microenvironment are enriched for methionine synthetic pathways, while having reduced S-adenosylmethionine metabolizing pathways. As methionine is one of nine essential amino acids that mammals are unable to synthesize de novo, we investigated a potentially novel function for the microbiome, supplying essential nutrients, such as methionine, to cancer cells. We demonstrate that LUAD cells can utilize methionine generated by bacteria to rescue phenotypes that would otherwise be inhibited due to nutrient restriction. In addition to this, with WT and metA mutant E. coli, we saw a selective advantage for bacteria with an intact methionine synthetic pathway to survive under the conditions induced by LUAD cells. These results would suggest that there is a potential bi-directional cross-talk between the local microbiome and adjacent tumor cells. In this study, we focused on methionine as one of the critical molecules, but we also hypothesize that additional bacterial metabolites may also be utilized by LUAD. Indeed, our radiolabeling data suggest that other biomolecules are shared between cancer cells and bacteria. Thus, modulating the local microbiome may have an indirect effect on tumor development, progression, and metastasis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Animais , Humanos , Metionina/genética , Metionina/metabolismo , Escherichia coli/metabolismo , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/patologia , Racemetionina/metabolismo , Proliferação de Células/genética , S-Adenosilmetionina/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Mamíferos/metabolismo , Microambiente Tumoral
15.
Drug Alcohol Depend ; 248: 109901, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37146499

RESUMO

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is implicated in neuronal and glial cell growth and differentiation, synaptic plasticity, and apoptotic mechanisms. A single-nucleotide polymorphism of the BDNF rs6265 gene may contribute to the pattern and magnitude of brain metabolite abnormalities apparent in those with an Alcohol Use Disorder (AUD). We predicted that methionine (Met) carriers would demonstrate lower magnetic resonance spectroscopy (MRS) measures of N-acetylaspartate level (NAA) and greater age-related decline in NAA than valine (Val) homozygotes. METHODS: Veterans with AUD (n=95; 46±12 years of age, min = 25, max = 71) were recruited from VA Palo Alto residential treatment centers. Single voxel MRS, at 3 Tesla, was used to obtain NAA, choline (Cho) and creatine (Cr) containing compounds from the left dorsolateral prefrontal cortex (DLPFC). Metabolite spectra were fit with LC Model and NAA and Cho were standardized to total Cr level and NAA was also standardized to Cho. RESULTS: Val/Met (n=35) showed markedly greater age-related decline in left DLPFC NAA/Cr level than Val/Val (n=60); no differences in mean metabolite levels were observed between Val/Met and Val/Val. Val/Met demonstrated greater frequency of history of MDD and higher frequency of cannabis use disorder over 12 months prior to study. CONCLUSIONS: The greater age-related decline in left DLPFC NAA/Cr and the higher frequency of MDD history and Cannabis Use disorder in BDNF rs6265 Met carriers with AUD are novel and may have implications for non-invasive brain stimulation targeting the left DLFPC and other psychosocial interventions typically utilized in the treatment of AUD.


Assuntos
Alcoolismo , Abuso de Maconha , Humanos , Metionina/genética , Córtex Pré-Frontal Dorsolateral , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Alcoolismo/genética , Racemetionina , Creatina/metabolismo
16.
J Neuroimaging ; 33(4): 652-660, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37158779

RESUMO

BACKGROUND AND PURPOSE: 11 C-methionine (MET)-PET is a useful tool in neuro-oncology. The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign on MRI is a characteristic finding in lower grade gliomas with isocitrate dehydrogenase (IDH) mutations and the absence of the 1p/19q codeletion; however, the T2-FLAIR mismatch sign has low sensitivity in differentiating gliomas and does not aid in identifying glioblastomas with IDH mutations. We therefore investigated the efficacy of the combination of the T2-FLAIR mismatch sign and MET-PET for accurately determining the molecular subtype of gliomas of all grades. METHODS: The present study comprised 208 adult patients diagnosed with supratentorial glioma confirmed by molecular genetics and histopathology. The ratio of the maximum lesion MET accumulation to the mean normal frontal cortex MET accumulation (T/N) was measured. The presence or absence of the T2-FLAIR mismatch sign was determined. The presence or absence of the T2-FLAIR mismatch sign and the MET T/N ratio were compared between glioma subtypes to evaluate individual and combined utility in identifying gliomas with IDH mutations and no 1p/19q codeletion (IDHmut-Noncodel) or gliomas with IDH mutations (IDHmut). RESULTS: The addition of MET-PET to MRI for the presence of the T2-FLAIR mismatch sign improved diagnostic accuracy, with the area under the curve values increasing from .852 to .871 for IDHmut-Noncodel and from .688 to .808 for IDHmut. CONCLUSIONS: The combination of the T2-FLAIR mismatch sign and MET-PET may provide improved diagnostic utility in differentiating gliomas according to molecular subtype, particularly in determining IDH mutation status.


Assuntos
Neoplasias Encefálicas , Glioma , Adulto , Humanos , Metionina/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Racemetionina , Isocitrato Desidrogenase/genética , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos
17.
Artigo em Inglês | MEDLINE | ID: mdl-37204832

RESUMO

A novel bacterium, designated 5-21aT, isolated from chitin-treated upland soil, exhibits methionine (Met) auxotrophy and chitinolytic activity. A physiological experiment revealed the cobalamin (synonym, vitamin B12)(Cbl)-auxotrophic property of strain 5-21aT. The newly determined complete genomic sequence indicated that strain 5-21aT possesses only the putative gene for Cbl-dependent Met synthase (MetH) and lacks that for the Cbl-independent one (MetE), which implies the requirement of Cbl for Met-synthesis in strain 5-21aT. The set of genes for the upstream (corrin ring synthesis) pathway of Cbl synthesis is absent in the genome of strain 5-21aT, which explains the Cbl-auxotrophy of 5-21aT. This strain was characterized via a polyphasic approach to determine its taxonomic position. The nucleotide sequences of two copies of the 16S rRNA gene of strain 5-21aT indicated the highest similarities to Lysobacter soli DCY21T(99.8 and 99.9 %) and Lysobacter panacisoli CJ29T(98.7 and 98.8 %, respectively), whose Cbl-auxotrophic properties were revealed in this study. The principal respiratory quinone was Q-8. The predominant cellular fatty acids were iso-C15:0, iso-C16:0 and iso-C17:1 ω9c. The complete genome sequence of strain 5-21aT revealed that the genome size was 4 155 451 bp long and the G+C content was 67.87 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain 5-21aT and its most closely phylogenetic relative L. soli DCY21T were 88.8 and 36.5%, respectively. Based on genomic, chemotaxonomic, phenotypic and phylogenetic data, strain 5-21aT represents a novel species in the genus Lysobacter, for which the name Lyobacter auxotrophicus sp. nov. is proposed. The type strain is 5-21aT (=NBRC 115507T=LMG 32660T).


Assuntos
Ácidos Graxos , Lysobacter , Ácidos Graxos/química , Fosfolipídeos/análise , Metionina/genética , Filogenia , RNA Ribossômico 16S/genética , Quitina , Vitamina B 12 , Análise de Sequência de DNA , Composição de Bases , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Genômica , Racemetionina , Vitaminas , Microbiologia do Solo
18.
Eur J Nucl Med Mol Imaging ; 50(6): 1709-1719, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36697961

RESUMO

PURPOSE: This study aimed to describe 11C-methionine (11C-MET) PET imaging characteristics in patients with paediatric diffuse intrinsic pontine glioma (DIPG) and correlate them with survival and H3 K27M mutation status. METHODS: We retrospectively analysed 98 children newly diagnosed with DIPG who underwent 11C-MET PET. PET imaging characteristics evaluated included uptake intensity, uniformity, metabolic tumour volume (MTV), and total lesion methionine uptake (TLMU). The maximum, mean, and peak of the tumour-to-background ratio (TBR), calculated as the corresponding standardised uptake values (SUV) divided by the mean reference value, were also recorded. The associations between the PET imaging characteristics and clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) and H3 K27M mutation status were assessed, respectively. RESULTS: In univariate analysis, imaging characteristics significantly associated with shorter PFS and OS included a higher uniformity grade, higher TBRs, larger MTV, and higher TLMU. In multivariate analysis, larger MTV at diagnosis, shorter symptom duration, and no treatment were significantly correlated with shorter PFS and OS. The PET imaging features were not correlated with H3 K27M mutation status. CONCLUSION: Although several imaging features were significantly associated with PFS and OS, only MTV, indicating the size of the active tumour, was identified as a strong independent prognostic factor.


Assuntos
Neoplasias Encefálicas , Glioma Pontino Intrínseco Difuso , Glioma , Humanos , Criança , Metionina/genética , Neoplasias Encefálicas/genética , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/metabolismo , Estudos Retrospectivos , Glioma Pontino Intrínseco Difuso/diagnóstico por imagem , Glioma Pontino Intrínseco Difuso/genética , Racemetionina , Tomografia por Emissão de Pósitrons , Mutação
19.
J Integr Plant Biol ; 65(1): 150-166, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36103229

RESUMO

The ethylene insensitive 3/ethylene insensitive 3-like (EIN3/EIL) plays an indispensable role in fruit ripening. However, the regulatory mechanism that links post-translational modification of EIN3/EIL to fruit ripening is largely unknown. Here, we studied the expression of 13 MaEIL genes during banana fruit ripening, among which MaEIL9 displayed higher enhancement particularly in the ripening stage. Consistent with its transcript pattern, abundance of MaEIL9 protein gradually increased during the ripening process, with maximal enhancement in the ripening. DNA affinity purification (DAP)-seq analysis revealed that MaEIL9 directly targets a subset of genes related to fruit ripening, such as the starch hydrolytic genes MaAMY3D and MaBAM1. Stably overexpressing MaEIL9 in tomato fruit hastened fruit ripening, whereas transiently silencing this gene in banana fruit retarded the ripening process, supporting a positive role of MaEIL9 in fruit ripening. Moreover, oxidation of methionines (Met-129, Met-130, and Met-282) in MaEIL9 resulted in the loss of its DNA-binding capacity and transcriptional activation activity. Importantly, we identified MaEIL9 as a potential substrate protein of methionine sulfoxide reductase A MaMsrA4, and oxidation of Met-129, Met-130, and Met-282 in MaEIL9 could be restored by MaMsrA4. Collectively, our findings reveal a novel regulatory network controlling banana fruit ripening, which involves MaMsrA4-mediated redox regulation of the ethylene signaling component MaEIL9.


Assuntos
Musa , Musa/genética , Musa/metabolismo , Metionina/genética , Metionina/metabolismo , Proteínas de Plantas/metabolismo , Frutas/metabolismo , Racemetionina/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas
20.
Childs Nerv Syst ; 39(7): 1711-1718, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36538104

RESUMO

BACKGROUND: To investigate the association of folate metabolism gene polymorphism with neural tube defects (NTDs) in Chinese population. METHODS: The subjects were divided into two groups, 495 children with NTDs (NTD group) and 255 healthy children (control group). RESULTS: The levels of folic acid, s-adenosine methionine (SAM), and Sam/s-adenosine homocysteine (SAH) in NTD group were lower than those in control group. There were significant differences in hey, SAH, and Sam levels between two groups, but there was no significant difference in folic acid content. High fever in early pregnancy, taking antiepileptic drugs, father's exposure to organic solvents, folic acid deficiency, and mother's diabetes were the important risk factors in NTDs. MTHFR 677C > T gene was a risk factor for NTD in children, while 1298A > C gene was a protective factor. CONCLUSION: Folic acid metabolism markers were different in NTD children and their mothers, and the overall trend showed that folate, SAM, and SAM/SAH levels were decreased, while Hcy and SAH levels were increased; MTHFR 677C > T gene of SNPs was a risk factor for the occurrence of NTDs, and MTHFR 1298A > C gene was a protective factor, and the environmental risk factor had a synergistic effect on occurrence of NTDs.


Assuntos
Ácido Fólico , Defeitos do Tubo Neural , Criança , Feminino , Gravidez , Humanos , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/genética , Polimorfismo de Nucleotídeo Único/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Fatores de Risco , Metionina/genética , Estudos de Casos e Controles
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