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Front Cardiovasc Med ; 11: 1445366, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39439669

RESUMO

A 56-year-old man with a 5-year history of paroxysmal palpitations, which have worsened over the past year, was diagnosed with atrial fibrillation. During evaluation, transesophageal echocardiography revealed a left atrium (LA) tumoral mass attached to the atrial septal fossa ovale, with intra-tumoral blood flow and blood stream draining from the mass. Both coronary computed tomography angiography and coronary angiography demonstrated a coro-cameral fistula connection between the left circumflex artery (LCX) branch and the LA. In addition, they showed feeding arteries of the mass arising from the LCX. The patient underwent surgical resection of the LA mass and repair of the coronary artery fistula. Intraoperative exploration revealed a 1.7 cm × 1.0 cm jelly-like, brittle LA mass and confirmed a rupture of the supplying artery, leading to a coronary artery-left atrial fistula. Surgical ligation was executed to ensure complete sealing of the supplying coronary branch within the atrial septum. Histopathological examination confirmed the diagnosis of left atrial myxoma. The 6-month follow-up indicated no recurrence of the myxoma and restoration of sinus rhythm after radiofrequency ablation. In the literature, cases of a left circumflex artery branch-left atrial fistula due to rupture of the artery supplying a left atrial myxoma are rare.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39475531

RESUMO

Traditional metal-organic frameworks (MOFs) preparation is generally time-consuming, polluting, and lacking specificity for enzyme immobilization. This paper introduced a facile, rapid, and green method to produce three MOFs subsequently employed to purify and coimmobilize recombinant glycosyltransferase (UGT) and recombinant sucrose synthetase (SUSy) using histidine tag (His-tag) for the specific adsorption of Ni2+ and Co2+ from MOFs. This method simplified enzyme purification from crude extracts and enabled enzymes to be reused. The results demonstrated that NiCo-MOF exhibited a higher enzyme load (115.9 mg/g) than monometallic MOFs. Additionally, the NiCo-MOF@UGT&SUSy demonstrated excellent stability and efficiently produced the rare ginsenoside Rh2 by catalyzing a coupling reaction (95.6 µg/mL), solving the problem of the substrate cost of uridine diphosphate glucose (UDPG). The NiCo-MOF@UGT&SUSy retained 68.97% of the initial activity after 10 cycles. Finally, molecular docking studies elucidated the conversion mechanism of the target product Rh2. This technique is important in the industrialization of ginsenoside production and enzyme purification.

4.
Sci Rep ; 14(1): 22715, 2024 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-39349542

RESUMO

Racial and ethnic disparities persist in cancer survival rates across the United States, despite overall improvements. This comprehensive analysis examines trends in 5-year relative survival rates from 2002-2006 to 2015-2019 for major cancer types, elucidating differences among racial/ethnic groups to guide equitable healthcare strategies. Data from the SEER Program spanning 2000-2020 were analyzed, focusing on breast, colorectal, prostate, lung, pancreatic cancers, non-Hodgkin lymphoma, acute leukemia, and multiple myeloma. Age-standardized relative survival rates were calculated to assess racial (White, Black, American Indian/Alaska Native, Asian/Pacific Islander) and ethnic (Hispanic, Non-Hispanic) disparities, utilizing period analysis for recent estimates and excluding cases identified solely through autopsy or death certificates. While significant survival improvements were observed for most cancers, notable disparities persisted. Non-Hispanic Blacks exhibited the largest gain in breast cancer survival, with an increase of 5.2% points (from 77.6 to 82.8%); however, the survival rate remained lower than that of Non-Hispanic Whites (92.1%). Colorectal cancer survival declined overall (64.7-64.1%), marked by a 6.2% point drop for Non-Hispanic American Indian/Alaska Natives (66.3-60.1%). Prostate cancer survival declined across all races, with Non-Hispanic American Indian/Alaska Natives showing a decrease of 7.7% points (from 96.9 to 89.2%). Lung cancer, acute leukemia, and multiple myeloma showed notable increases across groups. Substantial racial/ethnic disparities in cancer survival underscore the notable need for tailored strategies ensuring equitable access to advanced treatments, particularly addressing significant trends in colorectal and pancreatic cancers among specific minority groups. Careful interpretation of statistical significance is warranted given the large dataset.


Assuntos
Neoplasias , Programa de SEER , Feminino , Humanos , Masculino , Etnicidade/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/tendências , Neoplasias/mortalidade , Neoplasias/etnologia , Grupos Raciais/estatística & dados numéricos , Taxa de Sobrevida , Estados Unidos/epidemiologia
5.
J Clin Oncol ; : JCO2302313, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39255450

RESUMO

PURPOSE: The benefit of adjuvant therapy for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) remains unclear because of severely limited evidence. Although biologically distinct entities, adjuvant therapy practices for IPMN-derived PDAC are largely founded on pancreatic intraepithelial neoplasia-derived PDAC. We aimed to evaluate the role of adjuvant chemotherapy in IPMN-derived PDAC. METHODS: This international multicenter retrospective cohort study (2005-2018) was conceived at the Verona Evidence-Based Medicine meeting. Cox regressions were performed to identify risk-adjusted hazard ratios (HR) associated with overall survival (OS). Kaplan-Meier curves and log-rank tests were employed for survival analysis. Logistic regression was performed to identify factors motivating adjuvant chemotherapy administration. A decision tree was proposed and categorized patients into overtreated, undertreated, and optimally treated cohorts. RESULTS: In 1,031 patients from 16 centers, nodal disease (HR, 2.88, P < .001) and elevated (≥37 to <200 µ/mL, HR, 1.44, P = .006) or markedly elevated (≥200 µ/mL, HR, 2.53, P < .001) carbohydrate antigen 19-9 (CA19-9) were associated with worse OS. Node-positive patients with elevated CA19-9 had an associated 34.4-month improvement in median OS (P = .047) after adjuvant chemotherapy while those with positive nodes and markedly elevated CA19-9 had an associated 12.6-month survival benefit (P < .001). Node-negative patients, regardless of CA19-9, did not have an associated benefit from adjuvant chemotherapy (all P > .05). Based on this model, we observed undertreatment in 18.1% and overtreatment in 61.2% of patients. Factors associated with chemotherapy administration included younger age, R1-margin, poorer differentiation, and nodal disease. CONCLUSION: Almost half of patients with resected IPMN-derived PDAC may be overtreated or undertreated. In patients with node-negative disease or normal CA19-9, adjuvant chemotherapy is not associated with a survival benefit, whereas those with node-positive disease and elevated CA19-9 have an associated benefit from adjuvant chemotherapy. A decision tree was proposed. Randomized controlled trials are needed for validation.

6.
Biosens Bioelectron ; 267: 116742, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39243450

RESUMO

Ferrous ions (Fe2⁺) accumulation and abnormal alterations in lipid droplets (LDs) are closely associated with ferroptosis. In the liver, excessive iron accumulation promotes oxidative stress and exacerbates lipid droplet accumulation, while the disruption of iron homeostasis may also affect the formation and size of lipid droplets, their increased number and size can exacerbate the severity of disease under fatty liver conditions. The leads to hepatocyte damage, further triggering liver inflammation, fibrosis, and ultimately resulting in cirrhosis and hepatocellular carcinoma. Therefore, real-time monitoring of iron ion and lipid droplet changes is crucial for assessing the severity of liver disease, disease progression, and understanding the mechanisms of ferroptosis. We have developed a fluorescent probe, NRFep, for real-time monitoring of iron ion fluctuations and visualization of lipid droplet changes in ferroptosis and liver disease models. NRFep is specific and sensitive to iron ions and exhibits excellent stability in both cells and animal models. In addition, NRFep can be used to monitor changes in iron ions and lipid droplets in mouse liver injury and fatty liver models. Through fluorescence lifetime imaging technology, NRFep can also study the dynamic changes of intracellular iron ion content. NRFep provides a powerful tool for studying ferroptosis and related diseases, and its unique dual-monitoring function opens up new possibilities for developing new diagnostic and therapeutic strategies.

7.
Plants (Basel) ; 13(18)2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39339591

RESUMO

Ethylene-insensitive 3/Ethylene-insensitive3-like proteins (EIN3/EIL) represent a group of transcription factors critical for the ethylene signaling transduction that manipulate downstream ethylene-responsive genes, thereby regulating plant growth, development, and stress responses. However, the identification, evolution, and divergence of the EIL family remain to be studied in Sorghum bicolor. Here, we identified eight SbEILs, which were expanded due to whole-genome-duplication (WGD) events. Characterization of the protein sequences and expression atlas demonstrates that the WGD-duplicated SbEILs could become divergent due to the differential expression patterns, rather than domain and motif architectures. Comparative expression analysis was performed between the RNA-seq data sets of internodes from several sorghum cultivars to understand the potential roles of SbEIL members in internode elongation and maturation. Our results identified SbEIL3 and 7 (the latter as a homolog of OsEIL7/OsEIL1) to be the highly expressed SbEIL genes in sorghum internodes and revealed a potential functional link between SbEIL7 and internode maturation. The co-expression analysis and comparative expression analysis with ethylene-regulated gene sets found that SbEIL7 was co-regulated with a set of ubiquitin-related protein degradation genes, suggesting possible involvement of SbEIL7 in protein degradation and processing during the post-anthesis stages. Altogether, our findings lay a foundation for future functional studies of ethylene signaling-mediated gene regulation and improvement of sorghum internode development.

8.
Int J Mol Sci ; 25(18)2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39337611

RESUMO

Treating diabetic wounds effectively remains a significant clinical challenge. Emerging studies suggest that microRNAs (miRNAs) play crucial roles in various physiological and pathological processes and hold promise as therapeutic tools. This study investigates the miRNA expression profile in keratinocytes using a cell model of diabetic wounds. Microarray analysis revealed that 43 miRNAs from wounded keratinocytes incubated under diabetic conditions (high glucose/hypoxia) exhibited a two-fold change in expression compared to those incubated under normal conditions (low glucose/normoxia). Quantitative RT-PCR confirmed significant differences in the expression of eight miRNAs, with miR-3138 and miR-3679-5p being further analyzed for their roles in keratinocyte migration. Transfection with a miR-3138 mimic and a miR-3679-5p inhibitor indicated that upregulation of miR-3138 and downregulation of miR-3679-5p enhance keratinocyte migration in both normal and diabetic wounds. Pathway and gene ontology (GO) analyses identified potential pathways and functional annotations associated with miR-3138 and miR-3679-5p in diabetic wound healing. Potential human gene targets of miR-3138 and miR-3679-5p were predicted using a three-way comparison of the TargetScan, miRDB, and DIANA databases. This study elucidates the miRNA expression signature of human keratinocytes in a diabetes-like environment, providing deeper insights into the pathogenesis of diabetic wounds.


Assuntos
Movimento Celular , Queratinócitos , MicroRNAs , Cicatrização , Queratinócitos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Cicatrização/genética , Movimento Celular/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Diabetes Mellitus/metabolismo , Diabetes Mellitus/genética , Ontologia Genética
9.
Plants (Basel) ; 13(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39273836

RESUMO

Growth-regulating factor (GRF) is a plant-specific family of transcription factors crucial for meristem development and plant growth. Sorghum (Sorghum bicolor L. Moench) is a cereal species widely used for food, feed and fuel. While sorghum stems are important biomass components, the regulation of stem development and the carbohydrate composition of the stem tissues remain largely unknown. Here, we identified 11 SbGRF-encoding genes and found the SbGRF expansion driven by whole-genome duplication events. By comparative analyses of GRFs between rice and sorghum, we demonstrated the divergence of whole-genome duplication (WGD)-derived OsGRFs and SbGRFs. A comparison of SbGRFs' expression profiles supports that the WGD-duplicated OsGRFs and SbGRFs experienced distinct evolutionary trajectories, possibly leading to diverged functions. RNA-seq analysis of the internode tissues identified several SbGRFs involved in internode elongation, maturation and cell wall metabolism. We constructed co-expression networks with the RNA-seq data of sorghum internodes. Network analysis discovered that SbGRF1, 5 and 7 could be involved in the down-regulation of the biosynthesis of cell wall components, while SbGRF4, 6, 8 and 9 could be associated with the regulation of cell wall loosening, reassembly and/or starch biosynthesis. In summary, our genome-wide analysis of SbGRFs reveals the distinct evolutionary trajectories of WGD-derived SbGRF pairs. Importantly, expression analyses highlight previously unknown functions of several SbGRFs in internode elongation, maturation and the potential involvement in the metabolism of the cell wall and starch during post-anthesis stages.

11.
Microorganisms ; 12(9)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39338468

RESUMO

Red root rot disease is a devastating fungal disease of rubber trees caused by Ganoderma pseudoferreum (Wakef). Biocontrols using beneficial microorganisms are safe and sustainable. We isolated a DHR18 endophytic bacterium from a healthy rubber tree to obtain a new efficient antagonistic bacterium for red root rot disease affecting rubber trees and evaluated the mechanism of action involved using a double culture assay, genome annotation analysis, and the ethyl acetate extraction method. The results revealed that the DHR18 strain inhibits G. pseudoferreum growth and has broad-spectrum antifungal activity by secreting cell wall hydrolases (proteases and chitinases), indole-3-acetic acid, and siderophores. Furthermore, it fixes nitrogen and is involved in biofilm formation and phosphate solubilisation, improving disease resistance and tree growth. The results showed that the antifungal substances secreted by DHR18 are mainly lipopeptides. Simultaneously, DHR18 enhanced the rubber tree resistance to G. pseudoferreum by increasing the activities of defence enzymes superoxide dismutase, phenylalanine ammonia lyase, peroxidase, catalase, and polyphenol oxidase. The results indicate that B. arboris DHR18 has biocontrol potential and could be used as a candidate strain for the control of red root rot disease in rubber trees.

12.
Int J Mol Sci ; 25(15)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39125724

RESUMO

Auxin Response Factors (ARFs) make up a plant-specific transcription factor family that mainly couples perception of the phytohormone, auxin, and gene expression programs and plays an important and multi-faceted role during plant growth and development. Lemongrass (Cymbopogon flexuosus) is a representative Cymbopogon species widely used in gardening, beverages, fragrances, traditional medicine, and heavy metal phytoremediation. Biomass yield is an important trait for several agro-economic purposes of lemongrass, such as landscaping, essential oil production, and phytoremediation. Therefore, we performed gene mining of CfARFs and identified 26 and 27 CfARF-encoding genes in each of the haplotype genomes of lemongrass, respectively. Phylogenetic and domain architecture analyses showed that CfARFs can be divided into four groups, among which groups 1, 2, and 3 correspond to activator, repressor, and ETTN-like ARFs, respectively. To identify the CfARFs that may play major roles during the growth of lemongrass plants, RNA-seq was performed on three tissues (leaf, stem, and root) and four developmental stages (3-leaf, 4-leaf, 5-leaf. and mature stages). The expression profiling of CfARFs identified several highly expressed activator and repressor CfARFs and three CfARFs (CfARF3, 18, and 35) with gradually increased levels during leaf growth. Haplotype-resolved transcriptome analysis revealed that biallelic expression dominance is frequent among CfARFs and contributes to their gene expression patterns. In addition, co-expression network analysis identified the modules enriched with CfARFs. By establishing orthologous relationships among CfARFs, sorghum ARFs, and maize ARFs, we showed that CfARFs were mainly expanded by whole-genome duplications, and that the duplicated CfARFs might have been divergent due to differential expression and variations in domains and motifs. Our work provides a detailed catalog of CfARFs in lemongrass, representing a first step toward characterizing CfARF functions, and may be useful in molecular breeding to enhance lemongrass plant growth.


Assuntos
Cymbopogon , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Filogenia , Proteínas de Plantas , Cymbopogon/genética , Cymbopogon/metabolismo , Cymbopogon/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Desenvolvimento Vegetal/genética , Reguladores de Crescimento de Plantas/metabolismo , Perfilação da Expressão Gênica , Haplótipos
13.
Cell Death Differ ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143228

RESUMO

With advancements in genomics and immunology, immunotherapy has emerged as a revolutionary strategy for tumor treatment. However, pancreatic ductal adenocarcinoma (PDAC), an immunologically "cold" tumor, exhibits limited responsiveness to immunotherapy. This study aimed to address the urgent need to uncover PDAC's immune microenvironment heterogeneity and identify the molecular mechanisms driving immune evasion. Using single-cell RNA sequencing datasets and spatial proteomics, we discovered LIM domain only 7 (LMO7) in PDAC cells as a previously unrecognized driver of immune evasion through Treg cell enrichment. LMO7 was positively correlated with infiltrating regulatory T cells (Tregs) and dysfunctional CD8+ T cells. A series of in vitro and in vivo experiments demonstrated LMO7's significant role in promoting Treg cell differentiation and chemotaxis while inhibiting CD8+ T cells and natural killer cell cytotoxicity. Mechanistically, LMO7, through its LIM domain, directly bound and promoted the ubiquitination and degradation of Foxp1. Foxp1 negatively regulated transforming growth factor-beta (TGF-ß) and C-C motif chemokine ligand 5 (CCL5) expression by binding to sites 2 and I/III, respectively. Elevated TGF-ß and CCL5 levels contribute to Treg cell enrichment, inducing immune evasion in PDAC. Combined treatment with TGF-ß/CCL5 antibodies, along with LMO7 inhibition, effectively reversed immune evasion in PDAC, activated the immune response, and prolonged mouse survival. Therefore, this study identified LMO7 as a novel facilitator in driving immune evasion by promoting Treg cell enrichment and inhibiting cytotoxic effector functions. Targeting the LMO7-Foxp1-TGF-ß/CCL5 axis holds promise as a therapeutic strategy for PDAC. Graphical abstract revealing LMO7 as a novel facilitator in driving immune evasion by promoting Tregs differentiation and chemotaxis, inducing CD8+ T/natural killer cells inhibition.

14.
ACS Nano ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38988308

RESUMO

Metal-organic frameworks (MOFs) are a class of porous materials constructed from organic linkers and inorganic building blocks. Coordinative competition labilizes some MOFs under harsh chemical conditions because of their weak bonding. However, instability is not always a negative property of a material. In this study, we demonstrated the use of the acidic lability of MOFs for direct optical patterning. The controllable acid release from the photoacid generator at the exposed area causes bond cleavage between the linkers and metal ions/clusters, leading to solubility changes and pattern formation after development. This process avoids redundant steps and possible contamination in traditional photolithography, while maintaining the original properties of patterned MOFs. The preserved porosity and crystallinity promoted the development of MOFs for gas sensors and solid displays.

15.
Nat Commun ; 15(1): 2920, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575569

RESUMO

Metal-organic frameworks (MOFs) with diverse chemistry, structures, and properties have emerged as appealing materials for miniaturized solid-state devices. The incorporation of MOF films in these devices, such as the integrated microelectronics and nanophotonics, requires robust patterning methods. However, existing MOF patterning methods suffer from some combinations of limited material adaptability, compromised patterning resolution and scalability, and degraded properties. Here we report a universal, crosslinking-induced patterning approach for various MOFs, termed as CLIP-MOF. Via resist-free, direct photo- and electron-beam (e-beam) lithography, the ligand crosslinking chemistry leads to drastically reduced solubility of colloidal MOFs, permitting selective removal of unexposed MOF films with developer solvents. This enables scalable, micro-/nanoscale (≈70 nm resolution), and multimaterial patterning of MOFs on large-area, rigid or flexible substrates. Patterned MOF films preserve their crystallinity, porosity, and other properties tailored for targeted applications, such as diffractive gas sensors and electrochromic pixels. The combined features of CLIP-MOF create more possibilities in the system-level integration of MOFs in various electronic, photonic, and biomedical devices.

16.
J Am Soc Mass Spectrom ; 35(6): 1363-1369, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38683544

RESUMO

The sensitivity of the miniature mass spectrometer (mini-MS) is largely restricted by the ion transmission in rough vacuum region. Even though various "in-line" ion transfer devices have improved mini-MS sensitivity, the severe dynamic gas is still weakening the efficiency of ion transmission in this region. Inspired by the "off-axis" ion funnel design in the lab-scale mass spectrometers, a miniature orthogonal injection ion funnel (MO-IF) was developed in this study for the mini-MS with a continuous atmospheric pressure interface. Capable of directing injected ions by 90° and then transport them forward to the downstream skimmer, the MO-IF enabled the separation of ions from the dynamic gas flow jetted out of the inlet capillary. The key factors were optimized for the MO-IF, including the effects of RF amplitude, DC electric fields, and the position of the repeller. Under optimized conditions, the MO-IF minimized the negative effects of dynamic gas and improved the ion transmission efficiency by ∼2-fold in comparison with the in-line injection ion funnel. As a result, a lower limit of detection of 0.5 ng/mL were obtained with good linearity for hypaconitine. Additionally, the MO-IF further decreased the buffer gas pressure in the second vacuum chamber and improved the mass resolution by 1.1-1.5 times at different scan rates.

17.
Mikrochim Acta ; 191(4): 217, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38519619

RESUMO

Hypoxia, a significant feature of the tumor microenvironment, is closely associated with tumor growth, metastasis, and drug resistance. In the field of tumor microenvironment analysis, accurately imaging and quantifying hypoxia - a critical factor associated with tumor progression, metastasis, and resistance to therapy - remains a significant challenge. Herein, a hypoxia-activated red-emission fluorescent probe, ODP, for in vivo imaging of hypoxia in the tumor microenvironment is presented. Among various imaging methods, optical imaging is particularly convenient due to its rapid response and high sensitivity. The ODP probe specifically targets nitroreductase (AzoR), an enzyme highly expressed in hypoxic cells, playing a vital role by catalyzing the cleavage of azo bonds. The optical properties of ODP exhibited excellent performance in terms of fluorescence enhancement, fluorescence lifetime (0.81 ns), and detection limit (0.86 µM) in response to SDT. Cell imaging experiments showed that ODP could effectively detect and image intracellular hypoxia and the imaging capability of ODP was studied under various conditions including cell migration, antioxidant treatment, and different incubation times. Through comprehensive in vitro and in vivo experiments, including cellular imaging and mouse tumor models, this work demonstrates the efficacy of ODP in accurately detecting and imaging hypoxia. Moreover, ODP's potential in inducing apoptosis in cancer cells offers a promising avenue for integrating diagnostic and therapeutic strategies in cancer treatment. This innovative approach not only contributes to the understanding and assessment of tumor hypoxia but also opens new possibilities for targeted cancer therapy.


Assuntos
Corantes Fluorescentes , Neoplasias , Camundongos , Animais , Corantes Fluorescentes/química , Microambiente Tumoral , Microscopia de Fluorescência/métodos , Hipóxia , Imagem Óptica/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
18.
PLoS One ; 19(2): e0293894, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38381741

RESUMO

Modifications of mRNA, especially methylation of adenosine, have recently drawn much attention. The much rarer modification, 5-hydroxymethylation of cytosine (5hmC), is not well understood and is the subject of this study. Vertebrate Tet proteins are 5-methylcytosine (5mC) hydroxylases and catalyze the transition of 5mC to 5hmC in DNA. These enzymes have recently been shown to have the same function in messenger RNAs in both vertebrates and in Drosophila. The Tet gene is essential in Drosophila as Tet knock-out animals do not reach adulthood. We describe the identification of Tet-target genes in the embryo and larval brain by mapping one, Tet DNA-binding sites throughout the genome and two, the Tet-dependent 5hmrC modifications transcriptome-wide. 5hmrC modifications are distributed along the entire transcript, while Tet DNA-binding sites are preferentially located at the promoter where they overlap with histone H3K4me3 peaks. The identified mRNAs are preferentially involved in neuron and axon development and Tet knock-out led to a reduction of 5hmrC marks on specific mRNAs. Among the Tet-target genes were the robo2 receptor and its slit ligand that function in axon guidance in Drosophila and in vertebrates. Tet knock-out embryos show overlapping phenotypes with robo2 and both Robo2 and Slit protein levels were markedly reduced in Tet KO larval brains. Our results establish a role for Tet-dependent 5hmrC in facilitating the translation of modified mRNAs primarily in cells of the nervous system.


Assuntos
Citosina , Dioxigenases , Animais , Citosina/metabolismo , Drosophila/genética , Drosophila/metabolismo , Metilação de DNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Orientação de Axônios , Proteínas de Ligação a DNA/metabolismo , 5-Metilcitosina/metabolismo , DNA/metabolismo , Dioxigenases/genética
20.
J Fungi (Basel) ; 10(2)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38392830

RESUMO

Natural rubber is an important national strategic and industrial raw material. The leaf anthracnose of rubber trees caused by the Colletotrichum species is one of the important factors restricting the yields of natural rubber. In this study, we isolated and identified strain Bacillus velezensis SF334, which exhibited significant antagonistic activity against both C. australisinense and C. siamense, the dominant species of Colletotrichum causing rubber tree leaf anthracnose in the Hainan province of China, from a pool of 223 bacterial strains. The cell suspensions of SF334 had a significant prevention effect for the leaf anthracnose of rubber trees, with an efficacy of 79.67% against C. siamense and 71.8% against C. australisinense. We demonstrated that SF334 can lead to the lysis of C. australisinense and C. siamense mycelia by causing mycelial expansion, resulting in mycelial rupture and subsequent death. B. velezensis SF334 also harbors some plant probiotic traits, such as secreting siderophore, protease, cellulase, pectinase, and the auxin of indole-3-acetic acid (IAA), and it has broad-spectrum antifungal activity against some important plant pathogenic fungi. The genome combined with comparative genomic analyses indicated that SF334 possesses most genes of the central metabolic and gene clusters of secondary metabolites in B. velezensis strains. To our knowledge, this is the first time a Bacillus velezensis strain has been reported as a promising biocontrol agent against the leaf anthracnose of rubber trees caused by C. siamense and C. australisinense. The results suggest that B. velezensis could be a potential candidate agent for the leaf anthracnose of rubber trees.

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