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1.
ACS Omega ; 9(34): 36509-36517, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220489

RESUMEN

Microbially induced calcium carbonate precipitation (MICP) provides a novel approach for use in addressing the instabilities of borehole walls comprising broken formations, but the highly alkaline environments of drilling fluids are unfavorable for microbial growth. Therefore, this study investigated the alkali-resistant domestication of Bacillus pasteurii commonly used in MICP. Using gradient domestication, B. pasteurii was domesticated under different pH conditions (pH 8.0, 9.0, 10.0, and 11.0) in sodium carboxymethyl cellulose solid-free drilling fluids. Its growth patterns and variations in urease activity were analyzed to assess the effectiveness of domestication. The Gompertz and logistic models were used to fit the growth patterns of B. pasteurii under different pH conditions, and growth kinetic models were constructed based on the mean square error, Akaike information criterion, and coefficient of determination. The bacterial concentration and urease activity of B. pasteurii were enhanced after alkali-resistant gradient domestication. The Gompertz model accurately described the growth patterns of B. pasteurii after gradient domestication at pH 8.0, 10.0, and 11.0, whereas the logistic model accurately described the growth pattern after gradient domestication at pH 9.0. This study provides scientific evidence and a theoretical basis for the use of B. pasteurii in maintaining the stabilities of borehole walls comprising broken formations.

2.
Environ Int ; 191: 108964, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39173234

RESUMEN

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

3.
Hematology ; 29(1): 2381171, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39087796

RESUMEN

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease, for which identifying reliable prognostic markers is critical for accurate clinical prognosis and treatment optimization. The inhibition of emopamil-binding protein gene (EBP) expression has been demonstrated to induce cancer cell death via depleting downstream sterols. Nevertheless, no comprehensive studies have been conducted specifically in tumors, including AML. METHOD: Herein, survival analyses were performed on the dataset obtained from The Cancer Genome Atlas (TCGA). Besides, the EBP levels were quantified using real-time qPCR in a cohort of 120 AML patients, and the value of EBP was further assessed using our clinical data. RESULTS: Patients with high EBP expression had worse overall survival (OS) and event-free survival (EFS) than patients with low EBP expression, both in the TCGA dataset and our clinical data. Additionally, white blood cell (WBC) counts were higher in patients with high EBP expression (P = 0.032). Moreover, in patients with intermediate-risk AML, it was discovered that elevated EBP expression was linked to a worse EFS (P = 0.038). Multivariate analysis demonstrated that high EBP expression was an independent prognostic factor in AML patients and was associated with a shorter OS and EFS (OS: P = 0.041; EFS: P = 0.017). Furthermore, the data revealed that transplantation in the high-EBP group led to an improvement in survival (OS: P = 0.001; EFS: P = 0.001). The same benefit was also observed in intermediate-risk AML patients (OS: P = 0.026; EFS: P = 0.026). CONCLUSION: Collectively, our findings indicated that high expression of EBP in AML patients was an adverse prognostic factor, but transplantation had the otential to alleviate its negative effects.


Asunto(s)
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Adulto , Anciano , Biomarcadores de Tumor , Adulto Joven , Proteínas de Unión al ARN , Proteínas Adaptadoras Transductoras de Señales
4.
Med ; 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39151422

RESUMEN

BACKGROUND: Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a poor prognosis. To find a cure, we examined the synergistic effect of homoharringtonine (HHT) in combination with the BCL-2 inhibitor venetoclax (VEN) in ETP-ALL. METHODS: Using in vitro cellular assays and ETP-ALL xenograft models, we first investigated the synergistic activity of HHT and VEN in ETP-ALL. Next, to explore the underlying mechanism, we employed single-cell RNA sequencing of primary ETP-ALL cells treated with HHT or VEN alone or in combination and validated the results with western blot assays. Based on the promising preclinical results and given that both drugs have been approved for clinical use, we then assessed this combination in clinical practice. FINDINGS: Our results showed that HHT synergizes strongly with VEN both in vitro and in vivo in ETP-ALL. Mechanistic studies demonstrated that the HHT/VEN combination concurrently downregulated key anti-apoptotic proteins, i.e., MCL1, leading to enhanced apoptosis. Importantly, the clinical results were very promising. Six patients with ETP-ALL with either refractory/relapsed (R/R) or newly diagnosed disease were treated with an HHT/VEN-based regimen. All patients achieved complete remission (CR) after only one cycle of treatment. CONCLUSIONS: Our findings demonstrate that a combination of HHT/VEN is effective on ETP-ALL and represents the "backbone" of a promising and safe regimen for newly diagnosed and R/R patients with ETP-ALL. FUNDING: This work was funded by the National Cancer Institute, Gehr Family Foundation, George Hoag Family Foundation, National Natural Science Foundation of China, and Key Research and Development Program of Zhejiang Province of China.

5.
Ecotoxicol Environ Saf ; 282: 116691, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38981391

RESUMEN

Polymetallic contamination of soils caused by mining activities seriously threatens soil fertility, biodiversity and human health. Bioremediation is thought to be of low cost and has minimal environmental risk but its effectiveness needs to be improved. This study aimed to identify the combined effect of plant growth and microbial strains with different functions on the enhancement of bioremediation of polymetallic contaminated soil. The microbiological mechanism of bioremediation was explored by amplicon sequencing and gene prediction. Soil was collected from polymetallic mine wastelands and a non-contaminated site for use in a pot experiment. Remediation efficiency of this method was evaluated by planting ryegrass and applying a mixed bacterial consortium comprising P-solubilizing, N-fixing and SO4-reducing bacteria. The plant-microbe joint remediation method significantly enhanced the above-ground biomass of ryegrass and soil nutrient contents, and at the same time reduced the content of heavy metals in the plant shoots and soil. The application of the composite bacterial inoculum significantly affected the structure of soil bacterial communities and increased the bacterial diversity and complexity, and the stability of co-occurrence networks. The relative abundance of the multifunctional genera to which the strains belonged showed a significant positive correlation with the soil nutrient content. Genera related to carbon (C), nitrogen (N), phosphorus (P), and sulphur (S) cycling and heavy metal resistance showed an up-regulation trend in heavy metal-contaminated soils after the application of the mixed bacterial consortium. Also, bacterial strains with specific functions in the mixed consortium regulated the expression of genes involved in soil nutrient cycling, and thus assisted in making the soil self-sustainable after remediation. These results suggested that the remediation of heavy metal-contaminated soil needs to give priority to the use of multifunctional bacterial agents.


Asunto(s)
Biodegradación Ambiental , Lolium , Metales Pesados , Microbiología del Suelo , Contaminantes del Suelo , Contaminantes del Suelo/metabolismo , Metales Pesados/metabolismo , Suelo/química , Bacterias/metabolismo , Bacterias/genética , Consorcios Microbianos , Minería , Fósforo/metabolismo , Biomasa , Nitrógeno/metabolismo
6.
Blood ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968151

RESUMEN

We report on the antileukemic activity of homoharringtonine (HHT) in T-ALL. We showed that HHT inhibited NOTCH/MYC pathway and induced a significantly longer survival in T-ALL mouse and patient-derived xenograft models, therefore supporting HHT as a promising agent for T-ALL.

7.
Heliyon ; 10(11): e31748, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38961970

RESUMEN

To build a comprehensive framework for virtual power plant (VPP) development aligned with market dynamics and to devise effective strategies to foster its growth, this study undertakes several key steps. Firstly, it constructs a VPP development framework based on market conditions, to drive the evolution of new power systems and facilitating energy transformation. Secondly, through a blend of theoretical analysis and model construction, the fundamental principles of VPP are systematically elucidated, and a decision model for the VPP development framework, focusing on price demand response, is formulated. Lastly, an optimal scheduling model for the new power system is developed, with its efficacy validated across three distinct scenarios. The findings underscore the critical importance of integrating energy storage technologies, particularly pumped storage hydropower systems, for achieving balance and optimization within new power systems. Model verification reveals that the incorporation of energy storage power stations significantly enhances system stability and efficiency, particularly in addressing the volatility associated with renewable energy sources. Additionally, the analysis indicates that while the adoption of energy storage technologies may marginally increase overall power generation costs, the total power generation cost declines with the integration of battery storage and pumped storage hydropower stations. This suggests that leveraging energy storage technologies not only enhances system operational reliability but also contributes to reducing the overall cost of power production to a certain extent. In summary, this study presents an economic and environmentally sustainable scheduling model for new power systems within the context of market trading environments. By offering both theoretical insights and practical guidance, it aims to support sustainable development and energy transformation initiatives. Ultimately, the study is poised to foster the adoption of clean energy, facilitate the establishment of smart grids, and bolster the sustainable utilization of energy resources, thereby advancing environmental conservation efforts.

8.
Annu Rev Microbiol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38986128

RESUMEN

In 1952, Hershey and Chase used bacteriophage T2 genome delivery inside Escherichia coli to demonstrate that DNA, not protein, is the genetic material. Over 70 years later, our understanding of bacteriophage structure has grown dramatically, mainly thanks to the cryogenic electron microscopy revolution. In stark contrast, phage genome delivery in prokaryotes remains poorly understood, mainly due to the inherent challenge of studying such a transient and complex process. Here, we review the current literature on viral genome delivery across bacterial cell surfaces. We focus on icosahedral bacterial viruses that we arbitrarily sort into three groups based on the presence and size of a tail apparatus. We inventory the building blocks implicated in genome delivery and critically analyze putative mechanisms of genome ejection. Bacteriophage genome delivery into bacteria is a topic of growing interest, given the renaissance of phage therapy in Western medicine as a therapeutic alternative to face the antibiotic resistance crisis.

9.
Front Immunol ; 15: 1374390, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38868768

RESUMEN

Immunotherapy for hematological malignancies is a rapidly advancing field that has gained momentum in recent years, primarily encompassing chimeric antigen receptor T-cell (CAR-T) therapies, immune checkpoint inhibitors, and other modalities. However, its clinical efficacy remains limited, and drug resistance poses a significant challenge. Therefore, novel immunotherapeutic targets and agents need to be identified. Recently, N6-methyladenosine (m6A), the most prevalent RNA epitope modification, has emerged as a pivotal factor in various malignancies. Reportedly, m6A mutations influence the immunological microenvironment of hematological malignancies, leading to immune evasion and compromising the anti-tumor immune response in hematological malignancies. In this review, we comprehensively summarize the roles of the currently identified m6A modifications in various hematological malignancies, with a particular focus on their impact on the immune microenvironment. Additionally, we provide an overview of the research progress made in developing m6A-targeted drugs for hematological tumor therapy, to offer novel clinical insights.


Asunto(s)
Adenosina , Neoplasias Hematológicas , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/terapia , Adenosina/análogos & derivados , Adenosina/inmunología , Adenosina/metabolismo , Animales , Inmunoterapia/métodos
10.
Front Aging Neurosci ; 16: 1377719, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808034

RESUMEN

Background: The association between hypothyroidism and Parkinson's disease (PD) has sparked intense debate in the medical community due to conflicting study results. A better understanding of this association is crucial because of its potential implications for both pathogenesis and treatment strategies. Methods: To elucidate this complex relationship, we used Bayesian co-localisation (COLOC) and bidirectional Mendelian randomization (MR) analysis. COLOC was first used to determine whether hypothyroidism and PD share a common genetic basis. Subsequently, genetic variants served as instrumental variables in a bidirectional MR to explore causal interactions between these conditions. Results: COLOC analysis revealed no shared genetic variants between hypothyroidism and PD, with a posteriori probability of hypothesis 4 (PPH4) = 0.025. Furthermore, MR analysis indicated that hypothyroidism does not have a substantial causal effect on PD (OR = 0.990, 95% CI = 0.925, 1.060, p = 0.774). Conversely, PD appears to have a negative causal effect on hypothyroidism (OR = 0.776, 95% CI = 0.649, 0.928, p = 0.005). Conclusion: Our findings suggest the absence of shared genetic variants between hypothyroidism and PD. Interestingly, PD may inversely influence the risk of developing hypothyroidism, a finding that may inform future research and clinical approaches.

11.
Nat Commun ; 15(1): 2827, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565528

RESUMEN

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.


Asunto(s)
Bacteriófagos , Bacteriófagos/genética , Ecosistema , Fósforo , Metagenoma/genética , Suelo
12.
Res Sq ; 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38463957

RESUMEN

DEV is an obligatory lytic Pseudomonas phage of the N4-like genus, recently reclassified as Schitoviridae. The DEV genome encodes 91 ORFs, including a 3,398 amino acid virion-associated RNA polymerase. Here, we describe the complete architecture of DEV, determined using a combination of cryo-electron microscopy localized reconstruction, biochemical methods, and genetic knockouts. We built de novo structures of all capsid factors and tail components involved in host attachment. We demonstrate that DEV long tail fibers are essential for infection of Pseudomonas aeruginosa and dispensable for infecting mutants with a truncated lipopolysaccharide devoid of the O-antigen. We identified DEV ejection proteins and, unexpectedly, found that the giant DEV RNA polymerase, the hallmark of the Schitoviridae family, is an ejection protein. We propose that DEV ejection proteins form a genome ejection motor across the host cell envelope and that these structural principles are conserved in all Schitoviridae.

13.
J Mol Med (Berl) ; 102(3): 415-433, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38340163

RESUMEN

Previous evidence has confirmed that branched-chain aminotransferase-1 (BCAT1), a key enzyme governing branched-chain amino acid (BCAA) metabolism, has a role in cancer aggression partly by restricting αKG levels and inhibiting the activities of the αKG-dependent enzyme family. The oncogenic role of BCAT1, however, was not fully elucidated in acute myeloid leukemia (AML). In this study, we investigated the clinical significance and biological insight of BCAT1 in AML. Using q-PCR, we analyzed BCAT1 mRNAs in bone marrow samples from 332 patients with newly diagnosed AML. High BCAT1 expression independently predicts poor prognosis in patients with AML. We also established BCAT1 knockout (KO)/over-expressing (OE) AML cell lines to explore the underlying mechanisms. We found that BCAT1 affects cell proliferation and modulates cell cycle, cell apoptosis, and DNA damage/repair process. Additionally, we demonstrated that BCAT1 regulates histone methylation by reducing intracellular αKG levels in AML cells. Moreover, high expression of BCAT1 enhances the sensitivity of AML cells to the Poly (ADP-ribose) polymerase (PARP) inhibitor both in vivo and in vitro. Our study has demonstrated that BCAT1 expression can serve as a reliable predictor for AML patients, and PARP inhibitor BMN673 can be used as an effective treatment strategy for patients with high BCAT1 expression. KEY MESSAGES: High expression of BCAT1 is an independent risk factor for poor prognosis in patients with CN-AML. High BCAT1 expression in AML limits intracellular αKG levels, impairs αKG-dependent histone demethylase activity, and upregulates H3K9me3 levels. H3K9me3 inhibits ATM expression and blocks cellular DNA damage repair process. Increased sensitivity of BCAT1 high expression AML to PARP inhibitors may be used as an effective treatment strategy in AML patients.


Asunto(s)
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Antineoplásicos/farmacología , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , Reparación del ADN , Daño del ADN , Transaminasas/genética
14.
Metabolites ; 14(2)2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38393016

RESUMEN

Widespread exposure to organophosphorus flame retardants (OPFRs) has been observed in the general population. Emerging studies have revealed OPFRs possess endocrine-disturbing properties. The present study aims to assess the association between urinary metabolites of OPFRs, BMI, and serum lipid profiles. Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were obtained, with 1334 adults enrolled in the current study. Urinary concentrations of bis (1-chloro-2-propyl) phosphate (BCIPP), bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), dibutyl phosphate (DBUP), and diphenyl phosphate (DPHP) were quantified to assess OPFR exposure. Covariate-adjusted linear and logistic regression models were conducted to explore the associations between log2-transformed concentrations of OPFR metabolites, BMI, obesity, and serum lipid profiles. Stratified analyses were performed to assess the heterogeneity of associations by age, gender, race, etc. Positive associations were found between OPFR exposure and the risk of obesity. The multivariate linear analysis indicated that a one-unit increase in log2-transformed urinary concentrations of BCEP and BDCPP was associated with 0.27 (95% CI: 0.02-0.52, p = 0.0338) and 0.56 (95% CI: 0.25-0.87, p = 0.0004) higher BMI value, respectively. One log2-unit increase in urinary BCEP and BDCPP concentrations was associated with 1.1-fold (95% CI: 1.02-1.18, p = 0.0096) and 1.19-fold (95% CI: 1.09-1.30, p = 0.0001) risk for developing obesity. Furthermore, the non-linear relationship between exposure to OPFRs and obesity was identified. Additionally, multivariable linear regression showed that urinary DPHP concentrations were inversely correlated with serum triglyceride (TG) levels (ß = -7.41, 95% CI: -12.13 to -2.68, p = 0.0022). However, no other OPFR metabolites were found to be significantly statistically associated with serum lipid levels after adjusting for potential confounders. In conclusion, environmental exposure to OPFRs might contribute to obesity and dysregulated TG concentrations in adults. Future prospective research is warranted to confirm the causal relationship between metabolites of OPFRs and obesity.

15.
J Blood Med ; 15: 35-50, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38344181

RESUMEN

Background: Recently, an increasing number of studies have suggested dual-specificity phosphatase 23 (DUSP23) is a critical factor in the development of diffuse connective tissue disease and may be a valuable biomarker for primary human cancers. However, there is a lack of comprehensive studies on the prognostic significance of DUSP23 expression in acute myeloid leukemia (AML). Methods: RNA sequencing data from The Cancer Genome Atlas (TCGA) (AML = 173), Genotype-Tissue Expression (GTEx) (healthy controls = 70) and GEO (AML = 461, healthy controls = 76) databases were used to compare DUSP23 expression between AML patients and healthy controls. The overall survival (OS) of DUSP23 in AML was evaluated using Kaplan-Meier Cox regression. Furthermore, univariate Cox regression and multivariate Cox regression analysis were used to determine whether DUSP23 was an independent prognostic factor for AML. We then verified the expression level and prognostic significance of DUSP23 in our cohort (AML = 128, healthy controls = 31). In addition, functional enrichment analysis of DUSP23-related DEGs was performed through gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network analysis. Results: The expression level of DUSP23 is significantly higher in AML patients than in healthy controls in TCGA, GTEx, GEO databases and our cohort. By multivariate analysis, high expression of DUSP23 is a poor prognostic indicator of OS in the TCGA database. Next, we verified the role of DUSP23 as an adverse prognostic biomarker in our cohort. Enrichment analysis of related genes showed that DUSP23 may regulate important signal pathways in hematological tumors including the MAPK pathways. It is suggested by the PPI network that DUSP23, along with IMP3, MRPL4, MRPS12, POLR2L, and ATP5F1D may play a role in the process of AML. Conclusion: The study demonstrated high expression of DUSP23 could serve as a poor independent prognostic biomarker in AML.

16.
Sci Adv ; 10(2): eadi7606, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38198557

RESUMEN

Nuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in the nucleus. The ~360-angstrom HBV capsid translocates to the nuclear pore complex (NPC) as an intact particle, hijacking human importins in a reaction stimulated by host kinases. This paper describes the mechanisms of HBV capsid recognition by importins. We found that importin α1 binds a nuclear localization signal (NLS) at the far end of the HBV coat protein Cp183 carboxyl-terminal domain (CTD). This NLS is exposed to the capsid surface through a pore at the icosahedral quasi-sixfold vertex. Phosphorylation at serine-155, serine-162, and serine-170 promotes CTD compaction but does not affect the affinity for importin α1. The binding of 30 importin α1/ß1 augments HBV capsid diameter to ~620 angstroms, close to the maximum size trafficable through the NPC. We propose that phosphorylation favors CTD externalization and prompts its compaction at the capsid surface, exposing the NLS to importins.


Asunto(s)
Virus de la Hepatitis B , Nucleocápside , Humanos , Transporte Activo de Núcleo Celular , Carioferinas , Proteínas de la Cápside , Factores Inmunológicos , Serina
17.
Methods Mol Biol ; 2738: 215-228, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37966602

RESUMEN

Cryogenic electron microscopy (cryo-EM) single-particle analysis has revolutionized the structural analysis of icosahedral viruses, including tailed bacteriophages. In recent years, localized (or focused) reconstruction has emerged as a powerful data analysis method to capture symmetry mismatches and resolve asymmetric features in icosahedral viruses. Here, we describe the methods used to reconstruct the 2.65-MDa tail apparatus of the Shigella phage Sf6, a representative member of the Podoviridae superfamily.


Asunto(s)
Shigella , Siphoviridae , Virión , Proyectos de Investigación , Imagen Individual de Molécula
18.
Aging (Albany NY) ; 15(22): 13486-13503, 2023 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-38032290

RESUMEN

Ferroptosis induction through the suppression of glutathione peroxidase 4 (GPX4) and apoptosis-inducing factor mitochondria-associated 2 (AIFM2) has proven to be an effective approach in eliminating chemotherapy-resistant cells of various types. However, a comprehensive understanding of the roles of GPX4 and AIFM2 in acute myeloid leukemia (AML) has not yet been achieved. Using cBioPortal, DepMap, GEPIA, Metascape, and ONCOMINE, we compared the transcriptional expression, survival data, gene mutation, methylation, and network analyses of GPX4- and AIFM2-associated signaling pathways in AML. The results revealed that high expression levels of GPX4 and AIFM2 are associated with an adverse prognosis for AML patients. Overexpression of AIFM2 correlated with elevated mutation frequencies in NPM1 and DNMT3A. GPX4 upregulation modulated the following pathways: GO:0045333, cellular respiration; R-HSA-5389840, mitochondrial translation elongation; GO:0009060, aerobic respiration; R-HSA-9609507, protein localization; and R-HSA-8953854, metabolism of RNA. On the other hand, the overexpression of AIFM2 influenced the following processes: GO:0048704, embryonic skeletal system morphogenesis; GO:0021546, rhombomere development; GO:0009954, proximal/distal pattern formation; and GO:0048732, gland development. This study identifies the high expression of GPX4 and AIFM2 as novel biomarkers predicting a poor prognosis for AML patients. Furthermore, ferroptosis induction may improve the stratified treatment of AML.


Asunto(s)
Ferroptosis , Leucemia Mieloide Aguda , Humanos , Ferroptosis/genética , Leucemia Mieloide Aguda/genética , Pronóstico , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Mutación
19.
J Mol Biol ; 435(24): 168365, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37952769

RESUMEN

Bacteriophage P22 is a prototypical member of the Podoviridae superfamily. Since its discovery in 1952, P22 has become a paradigm for phage transduction and a model for icosahedral viral capsid assembly. Here, we describe the complete architecture of the P22 tail apparatus (gp1, gp4, gp10, gp9, and gp26) and the potential location and organization of P22 ejection proteins (gp7, gp20, and gp16), determined using cryo-EM localized reconstruction, genetic knockouts, and biochemical analysis. We found that the tail apparatus exists in two equivalent conformations, rotated by ∼6° relative to the capsid. Portal protomers make unique contacts with coat subunits in both conformations, explaining the 12:5 symmetry mismatch. The tail assembles around the hexameric tail hub (gp10), which folds into an interrupted ß-propeller characterized by an apical insertion domain. The tail hub connects proximally to the dodecameric portal protein and head-to-tail adapter (gp4), distally to the trimeric tail needle (gp26), and laterally to six trimeric tailspikes (gp9) that attach asymmetrically to gp10 insertion domain. Cryo-EM analysis of P22 mutants lacking the ejection proteins gp7 or gp20 and biochemical analysis of purified recombinant proteins suggest that gp7 and gp20 form a molecular complex associated with the tail apparatus via the portal protein barrel. We identified a putative signal transduction pathway from the tailspike to the tail needle, mediated by three flexible loops in the tail hub, that explains how lipopolysaccharide (LPS) is sufficient to trigger the ejection of the P22 DNA in vitro.


Asunto(s)
Bacteriófago P22 , Salmonella typhimurium , Bacteriófago P22/genética , Bacteriófago P22/química , Bacteriófago P22/metabolismo , Proteínas de la Cápside/química , Salmonella typhimurium/virología , Proteínas de la Cola de los Virus/genética
20.
BMC Genomics ; 24(1): 448, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37559017

RESUMEN

BACKGROUND: Previous studies have identified that chromosome structure plays a very important role in gene control. The transcription factor Yin Yang 1 (YY1), a multifunctional DNA binding protein, could form a dimer to mediate chromatin loops and active enhancer-promoter interactions. The deletion of YY1 or point mutations at the YY1 binding sites significantly inhibit the enhancer-promoter interactions and affect gene expression. To date, only a few computational methods are available for identifying YY1-mediated chromatin loops. RESULTS: We proposed a novel model named CapsNetYY1, which was based on capsule network architecture to identify whether a pair of YY1 motifs can form a chromatin loop. Firstly, we encode the DNA sequence using one-hot encoding method. Secondly, multi-scale convolution layer is used to extract local features of the sequence, and bidirectional gated recurrent unit is used to learn the features across time steps. Finally, capsule networks (convolution capsule layer and digital capsule layer) used to extract higher level features and recognize YY1-mediated chromatin loops. Compared with DeepYY1, the only prediction for YY1-mediated chromatin loops, our model CapsNetYY1 achieved the better performance on the independent datasets (AUC [Formula: see text]). CONCLUSION: The results indicate that CapsNetYY1 is an excellent method for identifying YY1-mediated chromatin loops. We believe that the CapsNetYY1 method will be used for predictive classification of other DNA sequences.


Asunto(s)
Secuencias Reguladoras de Ácidos Nucleicos , Factor de Transcripción YY1 , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismo , Inmunoprecipitación de Cromatina , Regiones Promotoras Genéticas , Cromatina/genética
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