Project description:Polyethylene pollutions are considered inert in nature and adversely affect the entire ecosystem. Larvae of greater wax moths (Galleria mellonella) have the ability to masticate and potentially biodegrade polyethylene films at elevated rates. The wax moth has been thought to metabolize PE independently of gut flora, however, the role of the microbiome is poorly understood and degradation by the wax moth might be involved. To determine whether the salivary glands of the wax moth were potentially involved in the PE degradation, it was investigated how surface changes of polyethylene were affected by mastication and consumption. Formation of pitting and degradation intermediates, including carbonyl groups, indicated that salivary glands could assist in polyethylene metabolism. We investigated the biochemical effect of exposure to PE on the composition of the salivary gland proteome. The expression of salivary proteins was found to be affected by PE exposure. The proteins that were significantly affected by the exposure to PE revealed that the wax moth is undergoing general changes in energy levels, and that enzymatic pathways associated with fatty acid beta oxidation were induced during PE consumption.
Project description:The study aimed to explore the potential of bacterial biodegradation as a solution to the global problem of plastic pollution, specifically targeting polyethylene (PE), one of the most common types of plastic. The goals of the study were to isolate a bacterial strain capable of breaking down PE, identify the key enzymes responsible for the degradation process, and understand the metabolic pathways involved.
Project description:Autophagy is a conserved intracellular degradation pathway exerting various cytoprotective and homeostatic functions by utilizing de novo double membrane vesicle (autophagosome) formation to target a wide range of cytoplasmic material for vacuolar/lysosomal degradation. The Atg1 kinase is one of its key regulators coordinating a complex signaling program to orchestrate autophagosome formation. Combining in vitro reconstitution and cell based approaches, we demonstrate that Atg1 is activated by lipidated Atg8 (Atg8-PE) stimulating substrate phosphorylation along the growing autophagosomal membrane. Atg1 dependent phosphorylation of Atg13 triggers Atg1 complex dissociation resulting in rapid turnover of Atg1 complex subunits at the pre-autophagosomal structure. Moreover, Atg1 recruitment by Atg8-PE self-regulates Atg8-PE levels in the growing autophagosomal membrane by phosphorylating and inhibiting the Atg8 specific E2 and E3. Taken together, our work uncovers the molecular basis for positive and negative feedback imposed by Atg1, and opposing phosphorylation and dephosphorylation events governing the spatiotemporal regulation of autophagy.
Project description:The study aimed to explore the potential of bacterial biodegradation as a solution to the global problem of plastic pollution, specifically targeting polyethylene (PE), one of the most common types of plastic. The goals of the study were to isolate a bacterial strain capable of breaking down PE, identify the key enzymes responsible for the degradation process, and understand the metabolic pathways involved. By investigating these aspects, researchers sought to gain critical insights that could be used to optimize plastic degradation conditions and inform the development of artificial microbial communities for effective bioremediation strategies. This research has significant relevance, as it addresses the pressing need for innovative and sustainable approaches to tackle the ever-growing issue of plastic waste and its impact on the environment.
Project description:We have developed a novel in vitro protocol for the derivation of bona fide Pharyngeal Endoderm (PE) cells from hESCs. We demonstrated that our PE cells robustly express Pharyngeal Endoderm markers, they are transcriptionally similar to PE cells isolated from in vivo mouse development and represent a transcriptionally homogeneous population. Importantly, we elucidated the contribution of Retinoic Acid in promoting a transcriptional and epigenetic rewiring of PE cells. In addition, we defined the epigenetic landscape of PE cells by combining ATAC-Seq and ChIP-Seq of histone marks.
Project description:We have developed a novel in vitro protocol for the derivation of bona fide Pharyngeal Endoderm (PE) cells from hESCs. We demonstrated that our PE cells robustly express Pharyngeal Endoderm markers, they are transcriptionally similar to PE cells isolated from in vivo mouse development and represent a transcriptionally homogeneous population. Importantly, we elucidated the contribution of Retinoic Acid in promoting a transcriptional and epigenetic rewiring of PE cells. In addition, we defined the epigenetic landscape of PE cells by combining ATAC-Seq and ChIP-Seq of histone marks.
Project description:We have developed a novel in vitro protocol for the derivation of bona fide Pharyngeal Endoderm (PE) cells from hESCs. We demonstrated that our PE cells robustly express Pharyngeal Endoderm markers, they are transcriptionally similar to PE cells isolated from in vivo mouse development and represent a transcriptionally homogeneous population. Importantly, we elucidated the contribution of Retinoic Acid in promoting a transcriptional and epigenetic rewiring of PE cells. In addition, we defined the epigenetic landscape of PE cells by combining ATAC-Seq and ChIP-Seq of histone marks.
Project description:Preeclampsia (PE), a multifactorial pregnancy-specific syndrome accounting for up to 8% of pregnancy complications, is a leading cause of maternal and fetal morbidity and mortality and PE is also associated with long-term risk of hypertension and stroke for both the mother and fetus. Currently, the only “cure” is delivery of the baby and placenta, largely because the pathogenesis of preeclampsia is not yet fully understood. Preeclampsia is associated with impaired vascular remodeling at the maternal-fetal interface and placental insufficiency; however, the specific factors that contribute to this impairment have not been identified. To identify potential contributing pathways, we examined temporal transcriptomic changes occurring within the uterus, uterine implantation sites, and placentae from the Dahl salt-sensitive (Dahl S) rat model of superimposed preeclampsia compared to Sprague Dawley (SD) rats. We hypothesized that the Dahl S maternal-fetal interface would exhibit a unique temporal transcriptomic profile unveiling novel biomarkers, therapeutic targets, and mechanistic pathways regarding the development of PE. Our initial study focused on evaluation of genes previously linked to the development PE from using real time quantitative PCR (RT qPCR) and total RNA was isolated from uterus (day 0), uterine implantation sites (days 7, 10, 14), and placenta (days 14 and 20). Subsequently, an unbiased transcriptome analysis was performed at each time point using whole genome microarray to identify novel factors involved in PE. 624, 332, 185 , and 366 genes were found to be differentially expressed on days 0, 7, 10 and 14 respectively, with a Reactome Pathway enrichment for “Fatty acid metabolism, Metabolism of water-soluble vitamins and cofactors, Metabolism, Synthesis of substrates in N-glucan biosynthesis on Day 7”; ”Glycerophospholipid biosynthesis, Phospholipid metabolism, and Metabolism of lipids on Day 10”; and “Metabolism of lipids, Phospholipid metabolism, degradation of the extracellular matrix, Fatty acid metabolism, and Collagen degradation on Day 14” in the Dahl S rat vs. SD. Our data revealed numerous pathways that may play a role in the pathophysiology of spontaneous superimposed PE and allow for further investigation of novel therapeutic targets and biomarker development.
Project description:We have developed a novel in vitro protocol for the derivation of bona fide Pharyngeal Endoderm (PE) cells from hESCs. We demonstrated that our PE cells robustly express Pharyngeal Endoderm markers, they are transcriptionally similar to PE cells isolated from in vivo mouse development and represent a transcriptionally homogeneous population. Importantly, we elucidated the contribution of Retinoic Acid in promoting a transcriptional and epigenetic rewiring of PE cells. In addition, we defined the epigenetic landscape of PE cells by combining ATAC-Seq and ChIP-Seq of histone marks. This SuperSeries is composed of the SubSeries listed below.
Project description:Introduction: To determine the miRNA expression profile in placentas complicated by Preeclampsia (PE) and compare it to uncomplicated pregnancies. Methods: Sixteen placentas from women with PE, including 11 with early onset PE (EOPE) and 5 with late onset PE (LOPE), as well as 8 from uncomplicated pregnancies were analyzed using miRNA microarrays. For statistical analyses the MATLAB® simulation environment was applied. The over-expression of miR-518a-5p was verified using Quantitative Real-Time Polymerase Chain Reaction. Results: Overall, 44 miRNAs were found deregulateddysregulated in PE complicated placentas. Statistical analysis revealed that miR-431, miR-518a-5p and miR-124* were over-expressed in EOPE complicated placentas as compared to controls whereas miR-544 and miR-3942 were down-regulated in EOPE. When comparing the miRNA expression profile in cases with PE and PE- growth restricted fetuses (FGR), miR-431 and miR-518a-5p were found over-expressed in pregnancies complicated by FGR. Additionally, up- regulation of miR-124, miR-423-3p and miR-518a-5p was associated with proteinuria. Discussion: Specific miRNAs can differentiate EOPE and LOPE from uncomplicated pregnancies representing putative PE-specific diagnostic biomarkers. Among them, miR-518a-5p emerged as a potential diagnostic indicator for EOPE cases as well as for FGR and proteinuria associated PE complicated placentas designating its potential link to the severity of the disease.