Most organisms rely on olfaction for survival and reproduction. The olfactory system of Drosophila melanogaster is one of the best characterized chemosensory systems and serves as a prototype for understanding insect olfaction. Olfaction in Drosophila is mediated by multigene families of odorant receptors and odorant binding proteins (OBPs). Although molecular response profiles of odorant receptors have been well documented, the contributions of OBPs to olfactory behavior remain largely unknown. Here, we used RNAi-mediated suppression of Obp gene expression and measurements of behavioral responses to 16 ecologically relevant odorants to systematically dissect the functions of 17 OBPs. We quantified the effectiveness of RNAi-mediated suppression by quantitative real-time polymerase chain reaction and used a proteomic liquid chromatography and tandem mass spectrometry procedure to show target-specific suppression of OBPs expressed in the antennae. Flies in which expression of a specific OBP is suppressed often show altered behavioral responses to more than one, but not all, odorants, in a sex-dependent manner. Similarly, responses to a specific odorant are frequently affected by suppression of expression of multiple, but not all, OBPs. These results show that OBPs are essential for mediating olfactory behavioral responses and suggest that OBP-dependent odorant recognition is combinatorial.
Cancer research in recent years has immensely benefited from the development of novel technologies that enable scientists to perform detailed investigations of genomes, transcriptomes, proteomes, and metabolomes. This has invariably furthered knowledge of tumorigenesis and etiology of cancer. The resulting information can, in the foreseeable future, effect a significant change in the pace of cancer research, thereby producing improvements in patient care. Ovarian cancer in particular has received the interest of the scientific community, being the most frequent cause of death from gynecological cancers, characterized by few early symptoms, diagnosis at an advanced stage, as well as poor prognosis. Ovarian cancer is a malignancy in which normal ovarian cells begin to grow in an uncontrolled, abnormal manner and produce tumors in one or both ovaries. Epithelial cancers, the most common ovarian cancers (>80%), develop from cells lining the ovarian surface. Most ovarian cancer research is primarily focused on the early detection and treatment of epithelial ovarian cancer, the more common ovarian malignancy. This review offers an introduction to ovarian cancer, with particular emphasis on human epithelial ovarian cancer. Current methods of detection and therapy are discussed. A survey of promising new protein, gene, and metabolite biomarkers on the horizon is provided. Future prospects for improved diagnosis are offered.
We report the development of split-less nano-flow liquid chromatography mass spectrometric analysis of glycans chemically cleaved from glycoproteins in plasma. Porous graphitized carbon operating under reverse-phase conditions and an amide-based stationary phase operating under hydrophilic interaction conditions are quantitatively compared for glycan separation. Both stationary phases demonstrated similar column efficiencies and excellent retention time reproducibility without an internal standard to correct for retention time shift. The 95% confidence intervals of the mean retention times were ±4 seconds across 5 days of analysis for both stationary phases; however, the amide stationary phase was observed to be more robust. The high mass measurement accuracy of less than 2 ppm and fragmentation spectra provided highly confident identifications along with structural information. In addition, data are compared amongst samples derived from 10 healthy controls, 10 controls with a differential diagnosis of benign gynecologic tumors, and 10 diseased epithelial ovarian cancer patients (EOC). Two fucosylated glycans were found to be up-regulated in healthy controls and provided an accurate diagnostic value with an area under the receiver operator characteristic curve of 0.87. However, these same glycans provided a significantly less diagnostic value when used to differentiate EOC from benign tumor control samples with an area under the curve of 0.73.
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