Kettering University

About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: Cancer & RNA. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.

Evolutionary flux of canonical microRNAs and mirtrons in Drosophila.

Abstract: Next-generation sequencing technologies generate vast catalogs of short RNA sequences from which to mine microRNAs. However, such data must be vetted to appropriately categorize microRNA precursors and interpret their evolution. A recent study annotated hundreds of microRNAs in three Drosophila species on the basis of singleton reads of heterogeneous length1. Our multi-million read datasets indicated that most of these were not substrates of RNAse III cleavage, and comprised many mRNA degradation fragments. We instead identified a distinct and smaller set of novel microRNAs supported by confident cloning signatures, including a high proportion of evolutionarily nascent mirtrons. Our data support a much lower rate in the emergence of lineage-specific microRNAs than previously inferred1, with a net flux of ~1 microRNA/million years of Drosophilid evolution.

Engrailed Homeobox Genes Regulate Establishment of the Cerebellar Afferent Circuit Map

Abstract: The spatial organization of the cerebellar afferent map has remarkable correspondence to two aspects of intrinsic patterning within the cerebellum embodied by a series of lobules and Purkinje cell (PC)-striped gene expression. Using male and female mice, we tested whether the Engrailed (En) homeobox genes are a common genetic substrate regulating all three systems, since they are expressed in spatially restricted domains within the cerebellum and are critical for patterning PC gene expression and foliation. Indeed, we discovered that En1/2 are necessary for the precise targeting of mossy fibers to distinct lobules, as well as their subsequent resolution into discrete parasagittal bands. Moreover, each En gene coordinately regulates afferent targeting and the striped pattern of PC protein expression (e.g., ZebrinII/AldolaseC) independent of regulating foliation. We further found that En1/2, rather than the presence of a full complement of lobules, are critical for generating PC protein stripes and mossy fiber bands, and that PC striped gene expression is determined before afferent banding. Thus, the En transcription factors not only regulate cerebellum circuit topography, but they also link afferent and efferent neurons precisely enough that alterations in PC protein expression can be used as a read out for underlying defects in circuitry. In summary, our data suggest that En1/2 are master regulators of three-dimensional organization of the cerebellum and coordinately regulate morphology, patterned gene expression, and afferent topography.

Convergent total synthesis of a tumour-associated mucin motif.

Abstract: Synthetic glycoconjugates that mimic cell-surface tumour antigens (glycolipids or glycoproteins with unusual carbohydrate structural motifs) have been shown to trigger humoral responses in murine and human immune systems1,2,3 This raises the exciting possibility of inducing active immunity with fully synthetic carbohydrate vaccines, particularly if vaccine compounds can be synthesized that resemble the surface environment of transformed cells even more closely Glycopeptides seem particularly suitable for this purpose In contrast to most glycolipids and thecarbohydrates themselves, glycopeptides bind to major histocompatibility complex molecules, and, in favourable cases, can stimulate T cells and lead to the expression of receptors that recognize the carbohydrate part of a glycopeptide with high specificity4,5,6,7,8 The preparation of glycopeptides and glycoproteins remains, however, a difficult challenge9,10,11,12: earlier synthesis methods have been inefficient, and established cloning approaches that allow engineering of global glycopatterns produce only heterogeneous glycoproteins13 Here we report an efficient strategy of the synthesis of tumour-associated mucin glycopeptides with clustered trisaccharide glycodomains corresponding to the (2,6)-sialyl T antigen Our approach involves construction of the complete glycodomain in the first stage, followed by convergent coupling to amino acid residues and subsequent incorporation of the glycosyl amino acid units into a peptide chain This general strategy allows the assembly of molecules in which selected glycoforms can be incorporated at any desired position of the peptide chain The resultant fully synthetic O-linked glycopeptide clusters are the closest homogeneous mimics of cell-surface mucins at present available, and so are promising compounds for the development of anticancer vaccines

The role of hormones in human behavior. I. Changes in female sexuality after adrenalectomy.

Abstract: Twenty-nine women, mean age 51 years, who had undergone total bilateral oophorectomy and adrenalectomy for metastatic breast cancer were interviewed about changes in their sexual desire, activity and responsiveness at an average period of twelve months after adrenal ablation. Of the 17 patients reportingsome sexual desire preoperatively, 14 experienced a decrease after surgery, the majority losing all desire. Of the 17 patients sexually active preoperatively, all reduced their frequency of intercourse postoperatively, almosthalf stopping entirety. Of the 12 patients responsive in intercourse preoperatively, 11 experienced a decrease after surgery, almost all becoming completely unresponsive. In each of these categories, the number of patients who lost sexual function entirely was statistically significant. Both sexual feelings and activities declined in all but 2 of the patients not already at zero levels among the 20 who obtained remission of metastatic disease after adrenalectomy, as well asin ...