Project description:Epidemiological evidence suggests that people chronically exposed to organophosphorus pesticides are at increased risk of neurodegenerative disease. Covalently linked amyloid beta dimers have been isolated from the brains of Alzheimer’s patients. The toxic forms of amyloid beta are amyloid dimers that spontaneously oligomerize. In the present report we treated recombinant and synthetic amyloid beta (1-42) with 1 mM chlorpyrifos oxon or 1 mM paraoxon. The trypsin-digested samples were analyzed by liquid chromatography tandem mass spectrometry on an Orbitrap Fusion Lumos mass spectrometer. Data were searched with Protein Prospector software. We found two new types of crosslinks in amyloid dimers. An isopeptide Asp-Asp link occurred between the N-terminal amine of Asp 1 in one peptide and the beta carboxyl group of Asp 1 in another peptide. An Asp-Arg link occurred between the guanidino group of Arg 5 in one peptide and the beta carboxyl group of Asp 1 in another peptide. These results show that the active metabolites of the pesticides chlorpyrifos and parathion catalyze the crosslinking of amyloid beta (1-42) into toxic dimers. It was concluded that the increased risk of neurodegenerative disease in people exposed to organophosphorus pesticides could be explained by the crosslinking activity of these chemicals.
Project description:In this study, we analyzed the microbial communities from a methane-based bio-reactor with selenate as an electron accepter. Four biological replicates were analyzed by metagenomics, of which data can be found in the SRA database (Accession number: SRP136677, SRP136696, SRP136790 and SRP136859). Based on the metagenomic data, we detected the expressed proteins using metaproteomics. This data is also included in this submission.
Project description:Pesticides are chemical compounds widely used in agriculture to control pests, since the 1960s. Regardless of its specific targets, such substances, unfortunately, can reach the human organism, and negative cumulative effects have been reported in people worldwide. Chronic exposure to pesticides has been discussed as a significant risk factor for the development of cancer, including breast tumors. Breast cancer is the most common malignant neoplasia that affects women worldwide, whose origin is mostly connected to life habits and the environment, and to a lesser extent to inheritable genetic mechanisms. Therefore, the contribution of substances as pesticides, that are present in the environment continuously, may have a pivotal role in the genesis breast cancer, especially in geographic areas in which women are important players in the rural work and are in direct contact with these compounds. In vitro and experimental studies have broadly reported the mechanisms triggered by pesticides that contribute to breast carcinogenesis, which fall essentially within DNA damage-based events in association with hormones deregulation and rising of metabolites that activate oncogenes (Alleva et al., 2018, BRADLOW et al., 1995). However, few is known about how these mechanisms are connected, as well as the manner that they can correlate with disease prognosis and clinicopathological features in human breast cancer as a result of the toxic consequences of pesticide exposure. In the last years, aiming to expand the knowledge about beyond isolated biological findings, high throughput molecular approaches combined with bioinformatics designs raised as powerful tools to understand breast cancer behavior and biology. Thereby, it was possible to broadcast that breast cancer is a very complex disease, and that distinct mechanisms are activated depending on specific clinicopathological characteristics. As far as we know, there are still no studies reporting the use of proteomics-based strategies to assess the impact of chronic pesticide exposure in women with breast cancer. To fill this gap, the present study proposes a toxicoproteomics perspective to investigate the systemic profile of differentially expressed proteins in the blood of breast cancer patients chronically exposed to pesticides, by using a high-throughput label-free proteomic strategy, and provide an integrative clinicopathological view based on bioinformatics approaches and validation experiments.
Project description:Permethrin and N,N-diethyl-meta-toluamide (DEET) are the pesticides and insect repellent most commonly used by humans. These pesticides have been shown to promote the epigenetic transgenerational inheritance of disease in rats. The current study was designed as an epigenome-wide association study (EWAS) to identify potential sperm differential DNA methylation regions (DMRs) for specific transgenerational disease. Outbred Sprague Dawley gestating female rats (F0) were exposed to the pesticide combination including Permethrin and DEET. Their great-grand offspring (F3) were only transgenerationally exposed to pesticides. The transgenerational adult male rat sperm were collected from individuals with single and multiple diseases and compared to non-diseased animals to identify DMRs associated with transgenerational disease transmission. The exposure of gestating female rats to a permethrin and DEET pesticide combination promoted testis disease, prostate disease, kidney disease, and the presence of multiple disease in the subsequent great-grand offspring F3 generation. Interestingly, the majority of the disease specific sperm DMR associated genes were previously found to be linked to relevant disease specific genes.
Project description:In this study we developed metaproteomics based methods for quantifying taxonomic composition of microbiomes (microbial communities). We also compared metaproteomics based quantification to other quantification methods, namely metagenomics and 16S rRNA gene amplicon sequencing. The metagenomic and 16S rRNA data can be found in the European Nucleotide Archive (Study number: PRJEB19901). For the method development and comparison of the methods we analyzed three types of mock communities with all three methods. The communities contain between 28 to 32 species and strains of bacteria, archaea, eukaryotes and bacteriophage. For each community type 4 biological replicate communities were generated. All four replicates were analyzed by 16S rRNA sequencing and metaproteomics. Three replicates of each community type were analyzed with metagenomics. The "C" type communities have same cell/phage particle number for all community members (C1 to C4). The "P" type communities have the same protein content for all community members (P1 to P4). The "U" (UNEVEN) type communities cover a large range of protein amounts and cell numbers (U1 to U4). We also generated proteomic data for four pure cultures to test the specificity of the protein inference method. This data is also included in this submission.
Project description:Exposure to environmental concentrations of organophosphate pesticides in Pacific salmon can cause neurobehavioral injuries leading to loss of survival. However, the molecular mechanisms underlying olfactory impairment remain poorly understood. In the current study, we exposed juvenile salmon to three environmentally-relevant doses of chlorpyrifos (CPF) and malathion (MAL) individually and to three concentrations of binary mixtures of both compounds. Brain acetylcholinesterase (AChE) activity was significantly reduced only in the highest dosage of binary mixture group (47% inhibition). Microarray analysis on RNA from coho olfactory rosettes revealed a number of differentially expressed genes in all exposure groups. Overall, there were little overlapping of affected canonical pathways between CPF groups and MAL groups, suggesting the different biofunctions targeted by these two OP pesticides. Several metabolic and signaling pathways also represented the significant toxicological impact of OP pesticides on olfactory system, such as Aryl Hydrocarbon Receptor Signaling, Xenobiotic Metabolism Signaling, Mitochondrial Dysfunction, Pro-Apoptosis, and Oxidative Stress.
Project description:Analyzing the US Center for Disease Control’s National Health and Nutrition Examination Survey chemical biomarker data, we identified a suite of toxicants, including metals, pesticides, and personal care product compounds, to which non-Hispanic Black women are disproportionately exposed. To characterize the impact of these toxicants on breast cancer pathways, we performed high throughput transcriptomic analysis of toxicant exposed breast cells.