Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:Omics approaches are broadly used to explore endocrine and toxicity-related pathways and functions. Nevertheless, there is still a significant gap in knowledge in terms of understanding the endocrine system and its numerous connections and intricate feedback loops, especially in non-model organisms. The fathead minnow (Pimephales promelas) is a widely used small fish model for aquatic toxicology and regulatory testing, particularly in North America. A draft genome has been published but the amount of available genomic or transcriptomic information is still far behind that of other more broadly studied species, such as the zebrafish. Here, we surveyed the tissue-specific proteome and transcriptome profiles in adult male fathead minnow. To do so, we generated a draft transcriptome using short and long sequencing reads. We also performed RNA sequencing and proteomics analysis on the telencephalon, hypothalamus, liver, and gut of male fish. The main purpose of this analysis was to generate tissue-specific omics data in order to support future aquatic ecotoxicogenomic and endocrine-related studies as well as to improve our understanding of the fathead minnow as an ecological model.
Project description:Seminal fluid proteins determine reproductive success in a wide range of animals. In the Drosophila male accessory gland, seminal fluid is mainly produced by two cell types, a vast majority of main cells and a small number of secondary cells that are characterized by a specialized secretory apparatus with unusually enlarged dense core granule vesicles. Loss of Abdominal-B expression from secondary cells in the enhancer mutant iab-6cocu disrupts their transcriptional and secretory identity. In consequence, mutant males fail to induce the long-term post-mating response, concomitant with loss of receptivity and sustained egg laying, in females. Here, we determine how secondary cells shape the seminal transferome and the female response by assessing iab-6cocu male accessory gland and female mate reproductive tract proteomes. We find downregulation of seminal fluid proteins constituting a signaling network that enables sperm binding and sustained action of key regulator Sex peptide and identify two new Sex peptide network proteins crucial for female fecundity, Cornutus (CG1701) and Hanrej (CG42564). Cornutus is required for dense core granule vesicle release, providing a link between the products of these compartments and the female long-term post-mating response. Our data highlights the importance of secondary cell signaling and secretion for overall seminal fluid composition and Sex peptide network function as well as the interdependence of main and secondary cells and their secretory products, advancing the general understanding of how seminal fluid signaling pathways modulate female physiology, sperm use and offspring production.
2026-01-15 | PXD072877 | Pride
Project description:Genome sequencing of Xylocopa virginica adult male