Production and Characterization of Desmalonichrome Relative Binding Affinity for Uranyl Ions in Relation to Other Siderophores

Siderophores are iron (Fe)-binding secondary metabolites that have been investigated for their uranium-binding properties. Previous work has focused on characterizing hydroxamate types of siderophores, such as desferrioxamine B, for their uranyl (UO₂)-binding affinity. Carboxylate forms of these metabolites hold potential to be more efficient chelators of UO₂, yet they have not been widely studied. Desmalonichrome is a carboxylate siderophore that is not commercially available and so was obtained from the fungus <i>Fusarium oxysporum</i> cultivated under Fe-depleted conditions. The relative affinity for UO₂ binding of desmalonichrome was investigated using a competitive analysis of binding affinities between UO₂ acetate and different concentrations of Fe­(III) chloride using electrospray ionization mass spectrometry. In addition to desmalonichrome, three other siderophores, including two hydroxamates (desferrioxamine B and desferrichrome) and one carboxylate (desferrichrome A), were studied to understand their relative affinities for the UO₂²⁺ ion at two pH values. The binding affinities of hydroxamate siderophores to UO₂²⁺ ions were observed to decrease with increasing Fe­(III)­Cl₃ concentration at the lower pH. On the other hand, decreasing the pH has a smaller impact on the binding affinities between carboxylate siderophores and the UO₂²⁺ ion. Desmalonichrome in particular was shown to have the greatest relative affinity for UO₂ at all pH and Fe­(III) concentrations examined. These results suggest that acidic functional groups in the ligands are important for strong chelation with UO₂ at lower pH

Choices within collective agreements a la carte in the Netherlands

Item does not contain fulltextInternational Symposium on Working Time 9th meeting "Flexibility in working time and the break-up of social time", 26 februari 2004Parijs : [S.n.]20 p

MOESM1 of A molecular genetic toolbox for Yarrowia lipolytica

Additional file 1. Supplemental figures

Table_1_The causal effect of air pollution on the risk of essential hypertension: a Mendelian randomization study.xlsx

BackgroundAir pollution poses a major threat to human health by causing various illnesses, such as cardiovascular diseases. While plenty of research indicates a correlation between air pollution and hypertension, a definitive answer has yet to be found.MethodsOur analyses were performed using the Genome-wide association study (GWAS) of exposure to air pollutants from UKB (PM2.5, PM10, NO2, and NOX; n = 423,796 to 456,380), essential hypertension from FinnGen (42,857 cases and 162,837 controls) and from UKB (54,358 cases and 408,652 controls) as a validated cohort. Univariable and multivariable Mendelian randomization (MR) were conducted to investigate the causal relationship between air pollutants and essential hypertension. Body mass index (BMI), alcohol intake frequency, and the number of cigarettes previously smoked daily were included in multivariable MRs (MVMRs) as potential mediators/confounders.ResultsOur findings suggested that higher levels of both PM2.5 (OR [95%CI] per 1 SD increase in predicted exposure = 1.24 [1.02–1.53], p = 3.46E-02 from Finn; OR [95%CI] = 1.04 [1.02–1.06], p = 7.58E-05 from UKB) and PM10 (OR [95%CI] = 1.24 [1.02–1.53], p = 3.46E-02 from Finn; OR [95%CI] = 1.04 [1.02–1.06], p = 7.58E-05 from UKB) were linked to an increased risk for essential hypertension. Even though we used MVMR to adjust for the impacts of smoking and drinking on the relationship between PM2.5 exposure and essential hypertension risks, our findings suggested that although there was a direct positive connection between them, it is not present after adjusting BMI (OR [95%CI] = 1.05 [0.87–1.27], p = 6.17E-01). Based on the study, higher exposure to PM2.5 and PM10 increases the chances of developing essential hypertension, and this influence could occur through mediation by BMI.ConclusionExposure to both PM2.5 and PM10 is thought to have a causal relationship with essential hypertension. Those impacted by substantial levels of air pollution require more significant consideration for their cardiovascular health.</p

Image_2_Immunogenic cell death related risk model to delineate ferroptosis pathway and predict immunotherapy response of patients with GBM.jpeg

Immunogenic cell death (ICD) is a type of cell death that leads to the regulation and activation of the immune response, which is marked by the exposure and delivery of damage‐associated molecular patterns (DAMPs) in the tumor microenvironment. Accumulating evidence has revealed the significance of ICD-related genes in tumor progression and therapeutic response. In this study, we obtained two ICD-related clusters for glioblastoma (GBM) by applying consensus clustering, and further constructed a risk signature on account of the prognostic ICD genes. Based on the risk signature, we found that higher risk scores were associated with worse patient prognosis. Besides, the results illustrated that ferroptosis regulators/markers were highly enriched the high-risk group, and ferroptosis were correlated with cytokine signaling pathway and other immune-related pathways. We also discovered that high-risk scores were correlated to specific immune infiltration patterns and good response to immune checkpoint blockade (ICB) treatment. In conclusion, our study highlights the significance of ICD-related genes as prognostic biomarkers and immune response indicators in GBM. And the risk signature integrating prognostic genes possessed significant potential value to predict the prognosis of patients and the efficacy of ICB treatment.</p

Image_1_Immunogenic cell death related risk model to delineate ferroptosis pathway and predict immunotherapy response of patients with GBM.jpeg

Immunogenic cell death (ICD) is a type of cell death that leads to the regulation and activation of the immune response, which is marked by the exposure and delivery of damage‐associated molecular patterns (DAMPs) in the tumor microenvironment. Accumulating evidence has revealed the significance of ICD-related genes in tumor progression and therapeutic response. In this study, we obtained two ICD-related clusters for glioblastoma (GBM) by applying consensus clustering, and further constructed a risk signature on account of the prognostic ICD genes. Based on the risk signature, we found that higher risk scores were associated with worse patient prognosis. Besides, the results illustrated that ferroptosis regulators/markers were highly enriched the high-risk group, and ferroptosis were correlated with cytokine signaling pathway and other immune-related pathways. We also discovered that high-risk scores were correlated to specific immune infiltration patterns and good response to immune checkpoint blockade (ICB) treatment. In conclusion, our study highlights the significance of ICD-related genes as prognostic biomarkers and immune response indicators in GBM. And the risk signature integrating prognostic genes possessed significant potential value to predict the prognosis of patients and the efficacy of ICB treatment.</p

Resin-Assisted Enrichment of N‑Terminal Peptides for Characterizing Proteolytic Processing

A resin-assisted enrichment method has been developed for specific isolation of protein N-terminal peptides to facilitate LC-MS/MS characterization of proteolytic processing, a major form of posttranslational modifications. In this method, protein thiols are blocked by reduction and alkylation, and protein lysine residues are converted to homoarginines. Protein N-termini are selectively converted to reactive thiol groups, and the thiol-containing N-terminal peptides are then captured by a thiol-affinity resin with high specificity (>97%). The efficiencies of these sequential reactions were demonstrated to be nearly quantitative. The resin-assisted N-terminal peptide enrichment approach was initially applied to a cell lysate of the filamentous fungus <i>Aspergillus niger</i>. Subsequent C-MS/MS analyses resulted in the identification of 1672 unique protein N-termini or proteolytic cleavage sites from 690 unique proteins

Image_1_Machine learning-based identification of SOX10 as an immune regulator of macrophage in gliomas.jpg

Gliomas, originating from the glial cells, are the most lethal type of primary tumors in the central nervous system. Standard treatments like surgery have not significantly improved the prognosis of glioblastoma patients. Recently, immune therapy has become a novel and effective option. As a conserved group of transcriptional regulators, the Sry-type HMG box (SOX) family has been proved to have a correlation with numerous diseases. Based on the large-scale machine learning, we found that the SOX family, with significant immune characteristics and genomic profiles, can be divided into two distinct clusters in gliomas, among which SOX10 was identified as an excellent immune regulator of macrophage in gliomas. The high expression of SOX10 is related to a shorter OS in LGG, HGG, and pan-cancer groups but benefited from the immunotherapy. It turned out in single-cell sequencing that SOX10 is high in neurons, M1 macrophages, and neural stem cells. Also, macrophages are found to be elevated in the SOX10 high-expression group. SOX10 has a positive correlation with macrophage cytokine production and negative regulation of macrophages’ chemotaxis and migration. In conclusion, our study demonstrates the outstanding cluster ability of the SOX family, indicating that SOX10 is an immune regulator of macrophage in gliomas, which can be an effective target for glioma immunotherapy.</p

Presentation_1_Tumor-secreted lactate contributes to an immunosuppressive microenvironment and affects CD8 T-cell infiltration in glioblastoma.pdf

IntroductionGlioblastoma is a malignant brain tumor with poor prognosis. Lactate is the main product of tumor cells, and its secretion may relate to immunocytes’ activation. However, its role in glioblastoma is poorly understood. MethodsThis work performed bulk RNA-seq analysis and single cell RNA-seq analysis to explore the role of lactate in glioblastoma progression. Over 1400 glioblastoma samples were grouped into different clusters according to their expression and the results were validated with our own data, the xiangya cohort. Immunocytes infiltration analysis, immunogram and the map of immune checkpoint genes’ expression were applied to analyze the potential connection between the lactate level with tumor immune microenvironment. Furthermore, machine learning algorithms and cell-cell interaction algorithm were introduced to reveal the connection of tumor cells with immunocytes. By co-culturing CD8 T cells with tumor cells, and performing immunohistochemistry on Xiangya cohort samples further validated results from previous analysis.DiscussionIn this work, lactate is proved that contributes to glioblastoma immune suppressive microenvironment. High level of lactate in tumor microenvironment can affect CD8 T cells’ migration and infiltration ratio in glioblastoma. To step further, potential compounds that targets to samples from different groups were also predicted for future exploration.</p

Image_3_Immunogenic cell death related risk model to delineate ferroptosis pathway and predict immunotherapy response of patients with GBM.jpeg

Immunogenic cell death (ICD) is a type of cell death that leads to the regulation and activation of the immune response, which is marked by the exposure and delivery of damage‐associated molecular patterns (DAMPs) in the tumor microenvironment. Accumulating evidence has revealed the significance of ICD-related genes in tumor progression and therapeutic response. In this study, we obtained two ICD-related clusters for glioblastoma (GBM) by applying consensus clustering, and further constructed a risk signature on account of the prognostic ICD genes. Based on the risk signature, we found that higher risk scores were associated with worse patient prognosis. Besides, the results illustrated that ferroptosis regulators/markers were highly enriched the high-risk group, and ferroptosis were correlated with cytokine signaling pathway and other immune-related pathways. We also discovered that high-risk scores were correlated to specific immune infiltration patterns and good response to immune checkpoint blockade (ICB) treatment. In conclusion, our study highlights the significance of ICD-related genes as prognostic biomarkers and immune response indicators in GBM. And the risk signature integrating prognostic genes possessed significant potential value to predict the prognosis of patients and the efficacy of ICB treatment.</p