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1.
Nucleic Acids Res ; 51(15): 7914-7935, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37351599

RESUMO

During the repair of DNA double-strand breaks (DSBs), de novo synthesized DNA strands can displace the parental strand to generate single-strand DNAs (ssDNAs). Many programmed DSBs and thus many ssDNAs occur during meiosis. However, it is unclear how these ssDNAs are removed for the complete repair of meiotic DSBs. Here, we show that meiosis-specific depletion of Dna2 (dna2-md) results in an abundant accumulation of RPA and an expansion of RPA from DSBs to broader regions in Saccharomyces cerevisiae. As a result, DSB repair is defective and spores are inviable, although the levels of crossovers/non-crossovers seem to be unaffected. Furthermore, Dna2 induction at pachytene is highly effective in removing accumulated RPA and restoring spore viability. Moreover, the depletion of Pif1, an activator of polymerase δ required for meiotic recombination-associated DNA synthesis, and Pif1 inhibitor Mlh2 decreases and increases RPA accumulation in dna2-md, respectively. In addition, blocking DNA synthesis during meiotic recombination dramatically decreases RPA accumulation in dna2-md. Together, our findings show that meiotic DSB repair requires Dna2 to remove ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis. Additionally, we showed that Dna2 also regulates DSB-independent RPA distribution.


Assuntos
Proteínas de Ligação a DNA , Proteínas de Saccharomyces cerevisiae , DNA , Reparo do DNA , DNA de Cadeia Simples/genética , Proteínas de Ligação a DNA/genética , Meiose/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(17): e2106902119, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35439061

RESUMO

Meiotic crossover (CO) recombination is tightly regulated by chromosome architecture to ensure faithful chromosome segregation and to reshuffle alleles between parental chromosomes for genetic diversity of progeny. However, regulation of the meiotic chromosome loop/axis organization is poorly understood. Here, we identify a molecular pathway for axis length regulation. We show that the cohesin regulator Pds5 can interact with proteasomes. Meiosis-specific depletion of proteasomes and/or Pds5 results in a similarly shortened chromosome axis, suggesting proteasomes and Pds5 regulate axis length in the same pathway. Protein ubiquitination is accumulated in pds5 and proteasome mutants. Moreover, decreased chromosome axis length in these mutants can be largely rescued by decreasing ubiquitin availability and thus decreasing protein ubiquitination. Further investigation reveals that two ubiquitin E3 ligases, SCF (Skp­Cullin­F-box) and Ufd4, are involved in this Pds5­ubiquitin/proteasome pathway to cooperatively control chromosome axis length. These results support the hypothesis that ubiquitination of chromosome proteins results in a shortened chromosome axis, and cohesin­Pds5 recruits proteasomes onto chromosomes to regulate ubiquitination level and thus axis length. These findings reveal an unexpected role of the ubiquitin­proteasome system in meiosis and contribute to our knowledge of how Pds5 regulates meiotic chromosome organization. A conserved regulatory mechanism probably exists in higher eukaryotes.


Assuntos
Complexo de Endopeptidases do Proteassoma , Ubiquitina , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Segregação de Cromossomos , Cromossomos/metabolismo , Meiose/genética , Complexo de Endopeptidases do Proteassoma/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ubiquitina/genética
3.
J Magn Reson Imaging ; 58(1): 301-310, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36259547

RESUMO

BACKGROUND: Meningiomas are frequently accompanied by peritumoral edema (PTE). The potential value of radiomic features of edema region in meningioma grading has not been investigated. PURPOSE: To investigate whether radiomic features of edema region contribute to grading meningiomas with PTE. STUDY TYPE: Retrospective. POPULATION: A total of 444 patients including 196 grade II and 248 WHO grade I meningiomas: 356 patients for training, 88 for validation. FIELD STRENGTH/SEQUENCE: A 1.5-T/3.0-T, noncontrast T1-weighted (T1WI), T2-weighted (T2WI), contrast-enhanced T1-weighted (T1CE) spin echo sequences. ASSESSMENT: A total of 851 radiomic features were extracted from each sequence on each region (tumor and edema region). These features were integrated by region respectively. Three subsets of clinical-radiomic features were constructed by joining clinical information (sex, age, tumor volume, and edema volume) and radiomic features of three regions: tumor, edema, and combined subsets. For each subset, features were filtered by the least absolute shrinkage and selection operator (LASSO) and Random Forest algorithm. Top 20 features of each subset were finally selected. STATISTICAL TESTS: Stochastic Gradient Boosting, Random Forest, and Bagged AdaBoost predictive models were built based on each subset. Discriminative abilities of models were quantified using receiver operating characteristics (ROC) and the area under the curve (AUC). A P value < 0.05 was considered statistically significant. RESULTS: Random Forest model based on combined subset (AUC [95% CI] = 0.880 [0.807-0.953]) had the best discriminative ability in grading meningiomas among the final models. The best model of edema subset and tumor subset were Random Forest model (AUC [95% CI] = 0.864 [0.791-0.938]) and Stochastic Gradient Boosting model (AUC [95% CI] = 0.844 [0.760-0.928]), respectively. DATA CONCLUSION: Radiomic features of edema region may contribute to grading meningiomas with PTE. The Random Forest model based on combined subset surpasses the best model based on tumor or edema subset regarding grading meningiomas with PTE. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/complicações , Meningioma/diagnóstico por imagem , Meningioma/patologia , Estudos Retrospectivos , Curva ROC , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Edema/diagnóstico por imagem , Imageamento por Ressonância Magnética
4.
Microb Cell Fact ; 21(1): 130, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761287

RESUMO

BACKGROUND: Lignocellulosic biomass is recognized as an effective potential substrate for biobutanol production. Though many pretreatment and detoxification methods have been set up, the fermentability of detoxicated lignocellulosic substrate is still far lower than that of starchy feedstocks. On the other hand, the number of recent efforts on rational metabolic engineering approaches to increase butanol production in Clostridium strains is also quite limited, demonstrating the physiological complexity of solventogenic clostridia. In fact, the strain performance is greatly impacted by process control. developing efficient process control strategies could be a feasible solution to this problem. RESULTS: In this study, oxidoreduction potential (ORP) controlling was applied to increase the fermentability of enzymatically hydrolyzed steam-exploded corn stover (SECS) for butanol production. When ORP of detoxicated SECS was controlled at - 350 mV, the period of fermentation was shortened by 6 h with an increase of 27.5% in the total solvent (to 18.1 g/L) and 34.2% in butanol (to 10.2 g/L) respectively. Silico modeling revealed that the fluxes of NADPH, NADH and ATP strongly differed between the different scenarios. Quantitative analysis showed that intracellular concentrations of ATP, NADPH/NADP+, and NADH/NAD+ were increased by 25.1%, 81.8%, and 62.5%. ORP controlling also resulted in a 2.1-fold increase in butyraldehyde dehydrogenase, a 1.2-fold increase in butanol dehydrogenase and 29% increase in the cell integrity. CONCLUSION: ORP control strategy effectively changed the intracellular metabolic spectrum and significantly improved Clostridium cell growth and butanol production. The working mechanism can be summarized into three aspects: First, Glycolysis and TCA circulation pathways were strengthened through key nodes such as pyruvate carboxylase [EC: 6.4.1.1], which provided sufficient NADH and NADPH for the cell. Second, sufficient ATP was provided to avoid "acid crash". Third, the key enzymes activities regulating butanol biosynthesis and cell membrane integrity were improved.


Assuntos
Butanóis , Clostridium acetobutylicum , 1-Butanol/metabolismo , Trifosfato de Adenosina/metabolismo , Butanóis/metabolismo , Clostridium/metabolismo , Clostridium acetobutylicum/metabolismo , Fermentação , NAD/metabolismo , NADP/metabolismo , Vapor , Zea mays/metabolismo
5.
Psychosom Med ; 83(3): 239-246, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657086

RESUMO

OBJECTIVE: Patients with diabetes mellitus with comorbid depression are at an increased risk of macrovascular and microvascular complications. Studies have suggested a positive association between depression and diabetic retinopathy (DR), but the evidence has not been systematically summarized. Therefore, the aim of the study was to perform a meta-analysis to investigate the correlation of depression with DR in patients with type 2 diabetes mellitus. METHODS: PubMed and EMBASE were searched for relevant studies through January 7, 2017. Fixed-effects and random-effects models were used to calculate overall odds ratio (OR) and confidence interval (CI). Subgroup analyses were conducted to examine whether the association was affected by adjustment for confounders or by age of study population. RESULTS: A total of 11 cross-sectional and prospective cohort studies were included in the analyses, with 34,185 individuals involved. Overall, patients with depression were at a significantly elevated risk of development of DR (fixed-effects OR = 1.50, 95% CI = 1.39-1.63; random-effects OR = 1.58, 95% CI = 1.35-1.84). The association did not vary by adjustment for confounders. However, a slightly larger pooled estimate was observed among studies with a mean age of <60 years (OR = 1.78, 95% CI = 1.46-2.07) than those with a mean age of ≥60 years (OR = 1.42, 95% CI = 1.16-1.75). CONCLUSIONS: Depression was significantly associated with an increased incidence of DR in patients with type 2 diabetes mellitus. However, the existing literature does not yet definitely document that whether depression contributes directly or indirectly to incident DR. Further prospective investigations identifying high-risk subgroups are warranted.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Estudos Transversais , Depressão/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Retinopatia Diabética/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
6.
J Plant Res ; 134(4): 729-736, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33590370

RESUMO

To obtain accurate spatially continuous reflectance from Unmanned Aerial Vehicle (UAV) remote sensing, UAV data needs to be integrated with the data on the ground. Here, we tested accuracy of two methods to inverse reflectance, Ground-UAV-Linear Spectral Mixture Model (G-UAV-LSMM) and Minimum Noise Fraction-Pixel Purity Index-Linear Spectral Mixture Model (MNF-PPI-LSMM). At wavelengths of 550, 660, 735 and 790 nm, which were obtained by UAV multispectral observations, we calculated the canopy abundance based on the two methods to acquire the inversion reflectance. The correlation of the inversion and measured reflectance values was stronger in G-UAV-LSMM than MNF-PPI-LSMM. We conclude that G-UAV-LSMM is the better model to obtain the canopy inversion reflectance.


Assuntos
Malus , Tecnologia de Sensoriamento Remoto , Modelos Lineares
7.
Artigo em Inglês | MEDLINE | ID: mdl-38885103

RESUMO

Graph neural networks (GNNs) have demonstrated efficient processing of graph-structured data, making them a promising method for electroencephalogram (EEG) emotion recognition. However, due to dynamic functional connectivity and nonlinear relationships between brain regions, representing EEG as graph data remains a great challenge. To solve this problem, we proposed a multi-domain based graph representation learning (MD 2 GRL) framework to model EEG signals as graph data. Specifically, MD 2 GRL leverages gated recurrent units (GRU) and power spectral density (PSD) to construct node features of two subgraphs. Subsequently, the self-attention mechanism is adopted to learn the similarity matrix between nodes and fuse it with the intrinsic spatial matrix of EEG to compute the corresponding adjacency matrix. In addition, we introduced a learnable soft thresholding operator to sparsify the adjacency matrix to reduce noise in the graph structure. In the downstream task, we designed a dual-branch GNN and incorporated spatial asymmetry for graph coarsening. We conducted experiments using the publicly available datasets SEED and DEAP, separately for subject-dependent and subject-independent, to evaluate the performance of our model in emotion classification. Experimental results demonstrated that our method achieved state-of-the-art (SOTA) classification performance in both subject-dependent and subject-independent experiments. Furthermore, the visualization analysis of the learned graph structure reveals EEG channel connections that are significantly related to emotion and suppress irrelevant noise. These findings are consistent with established neuroscience research and demonstrate the potential of our approach in comprehending the neural underpinnings of emotion.

8.
Environ Pollut ; 325: 121391, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36871747

RESUMO

To address conventional powder catalysts' recovery and aggregation issues that greatly restrain their practical application, a recoverable graphene oxide (GO)-supported 3D-MoS2/FeCo2O4 sponge (SFCMG) was developed through a simple impregnation pyrolysis method. SFCMG can efficiently activate peroxymonosulfate (PMS) to produce reactive species for rapid degradation of rhodamine B (RhB), with 95.0% and 100% of RhB being removed within 2 min and 10 min, respectively. The presence of GO enhances the electron transfer performance of the sponge, and the three-dimensional melamine sponge serves as a substrate to provide a highly dispersed carrier for FeCo2O4 and MoS2/GO hybrid sheets. SFCMG exhibits a synergistic catalytic effect of Fe and Co, and facilitates the redox cycles of Fe(III)/Fe(II) and Co(III)/Co(II) by MoS2 co-catalysis, which enhances its catalytic activity. Electron paramagnetic resonance results demonstrate that SO4•-, ·O2- and 1O2 are all involved in SFCMG/PMS system, and 1O2 played a prominent role in RhB degradation. The system has good resistance to anions (Cl-, SO42-, and H2PO4-) and humic acid and excellent performance for many typical contaminants degradation. Additionally, it works efficiently over a wide pH range (3-9) and possesses high stability and reusability with the metal leaching far below the safety standards. The present study extends the practical application of metal co-catalysis and offers a promising Fenton-like catalyst for the treatment of organic wastewater.


Assuntos
Poluentes Ambientais , Molibdênio , Compostos Férricos , Peróxidos
9.
World Neurosurg ; 162: e580-e586, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35307589

RESUMO

OBJECTIVE: It remains controversial whether patients with atypical meningiomas can benefit from postoperative radiotherapy (PORT) after gross total resection (GTR). This study aimed to explore the effectiveness of PORT in patients with atypical meningiomas after GTR based on our single-center data with a relatively large sample size. METHODS: Patients with atypical meningiomas who underwent GTR in our center were reviewed. Univariable and multivariable Cox proportional hazard models were conducted for survival analyses. Kaplan-Meier survival curves were generated, and 5-year progression-free survival (PFS) rates were calculated. RESULTS: This study enrolled 260 patients. PORT was not associated with PFS (P = 0.507). Sex (P = 0.006, hazard ratio 0.418, 95% confidence interval 0.224-0.781), age (P = 0.032, hazard ratio 1.032, 95% confidence interval 1.003-1.061), and tumor location (P = 0.026, hazard ratio 0.199, 95% confidence interval 0.048-0.824) were independent predictors of PFS. The 5-year PFS rate of patients receiving PORT (85.6%) was similar to that of patients not receiving PORT (84.8%). The 5-year PFS rate was 100% in patients with convexity atypical meningiomas regardless of whether or not they received PORT. CONCLUSIONS: PORT after GTR may not prolong PFS in patients with atypical meningiomas. Patients with convexity atypical meningiomas had favorable outcomes after GTR regardless of receipt of PORT.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Meningioma/patologia , Meningioma/radioterapia , Meningioma/cirurgia , Recidiva Local de Neoplasia/cirurgia , Radioterapia Adjuvante , Estudos Retrospectivos
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