ABSTRACT: This data set was collected on a qexactive coupled to a thermo vanquish. Data was collected in a DDA fashion in positive mode. The project itself revolved around compound 94NPD2, a compound that is similar to veraguamides
Project description:This data set was collected on a qexactive coupled to a Thermo vanquish. Data was collected in a DDA fashion in negative mode. The project itself revolved around compound 94NPD2, a compound that is similar to veraguamides
Project description:To elucidate the antivirulent lactone U1 mode of action, next generation sequencing was applied to analyze the transcriptome of NCTC 8325 cells treated with either compound or DMSO as control. Overall design: Two biological replicates for compound treated and also two biological replicates for DMSO treated Staphylococcus aureus cultures were analysed.
Project description:To elucidate the antivirulent hydroxy amide (R*,R*)-3 mode of action, next generation sequencing was applied to analyze the transcriptome of NCTC 8325 cells treated with either compound or DMSO as control. Overall design: Two biological replicates for compound treated and also two biological replicates for DMSO treated Staphylococcus aureus cultures were analysed.
Project description:Natural Killer cells are innate lymphocytes, participate in immune surveillance and elimination of stressed or transformed cells and critically shape the inflammatory cytokine environment to interact with cells of the innate and adaptive immune system, including macrophages, dendritic and Tcells. By performing a focused compound library screening, further validated by knockdown approaches, we here identify Jumonji-type histone 3 lysine 27 (H3K27) demethylases as key regulators of cytokine production in various human NK cell subsets. The prototypic H3K27 demethylase inhibitor GSK-J4 increases global levels of the repressive H3K27me3 mark around transcription start sites including NK cell effector cytokines, and thereby reduces IFN-γ, TNFα, GM-CSF and IL-10 levels in IL-15 stimulated NK cells whilst sparing the cytotoxic killing capacity against cancer cells. The anti-inflammatory effect of GSK-J4 in highly inflammatory NK cell subsets, isolated from peripheral blood or tissue from rheumatoid arthritis patients, coupled with an inhibitory effect on formation of bone-resorbing osteoclasts, suggests a wider role and utility of histone demethylase inhibition in immunity and inflammation. Overall design: We constructed 6 RNA-seq libraries; two conditions in triplicate. NK cells were cultured in media in the presence of IL-15 stimulation then cultured in the presence of DMSO and GSK-J4 treated NK cells. RNA was collected at 24 hours.
Project description:<p>The central aim in ecometabolomics and chemical ecology is to pinpoint chemical features that explain molecular functioning. The greatest challenge is the identification of compounds due to the lack of constitutive reference spectra, the large number of completely unknown compounds, and bioinformatic methods to analyze the big data. In this study we present an interdisciplinary methodological framework that extends ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) with data-dependent acquisition (DDA-MS) and the automated in silico classification of fragment peaks into compound classes. We synthesize findings from a prior study that explored the influence of seasonal variations on the chemodiversity of secondary metabolites in nine bryophyte species. Here we reuse and extend the representative dataset with DDA-MS data. Hierarchical clustering, heatmaps, dbRDA, and ANOVA with post-hoc Tukey HSD were used to determine relationships of the study factors species, seasons, and ecological characteristics. The tested bryophytes showed species-specific metabolic responses to seasonal variations (50% vs. 5% of explained variation). Marchantia polymorpha, Plagiomnium undulatum, and Polytrichum strictum were biochemically most diverse and unique. Flavonoids and sesquiterpenoids were upregulated in all bryophytes in the growing seasons. We identified ecological functioning of compound classes indicating light protection (flavonoids), biotic and pathogen interactions (sesquiterpenoids, flavonoids), low temperature and desiccation tolerance (glycosides, sesquiterpenoids, anthocyanins, lactones), and moss growth supporting anatomic structures (few methoxyphenols and cinnamic acids as part of proto-lignin constituents). The reusable bioinformatic framework of this study can differentiate species based on automated compound classification. Our study allows detailed insights into the ecological roles of biochemical constituents of bryophytes with regard to seasonal variations. We demonstrate that compound classification can be improved with adding constitutive reference spectra to existing spectral libraries. We also show that generalization on compound classes improves our understanding of molecular ecological functioning and can be used to generate new research hypotheses.</p>
Project description:We describe the development of a novel anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound is efficacious in a mouse model of visceral leishmaniasis, and has suitable physicochemical, pharmacokinetic and toxicological properties for further development and has been declared a preclinical candidate. Detailed mode of action studies indicate that compounds from this series act principally by inhibiting the parasite protein kinases.
Project description:This study investigated the ability of two novel adjuvant formulations, QCDC (Quil A/cholesterol/DDA/Carbopol) and QCDCR (QCDC/Bay R1005), in combination with a recombinant profilin vaccine, to modulate host protective immunity and to alter new gene expression during experimental avian coccidiosis. Overall design: Four-condition experiment, Profilin only vs. Non-vaccination, Profilin only vs. Co-vaccination of QCDC plus profilin, Profilin only vs. Co-vaccination of QCDCR plus profilin, Biological replicates: 2 profilin only replicates, 2 Non-vaccination replicates, 2 QCDC plus profilin replicates, 2 QCDCR plus profilin replicates with dye-switching.