339 research outputs found

    Compressed television transmission: A market survey

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    NASA's compressed television transmission technology is described, and its potential market is considered; a market that encompasses teleconferencing, remote medical diagnosis, patient monitoring, transit station surveillance, as well as traffic management and control. In addition, current and potential television transmission systems and their costs and potential manufacturers are considered

    Conserved and divergent functions of Drosophila atonal , amphibian, and mammalian Ath5 genes

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    Insect and vertebrate eyes differ in their formation, cellular composition, neural connectivity, and visual function. Despite this diversity, Drosophila atonal and its vertebrate Ortholog in the eye, Ath5 , each regulate determination of the first retinal neuron classβ€”R8 photo-receptors and retinal ganglion cells (RGCs)β€”in their respective organisms. We have performed a cross-species functional comparison of these genes. In ato 1 mutant Drosophila , ectopic Xenopus Ath5 ( Xath5 ) rescues photoreceptor cell development comparably with atonal . In contrast, mouse Ath5 ( Math5 ) induces formation of very few ommatidia, and most of these lack R8 cells. In the developing frog eye, ectopic atonal , like Xath5 , promotes the differentiation RGCs. Despite strong conservation of atonal , Xath5 , and Math5 structure and shared function, other factors must contribute to the species specificity of retinal neuron determination. These observations suggest that the atonal family may occupy a position in a gene hierarchy where differences in gene regulation or function can be correlated with evolutionary diversity of eye development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72909/1/j.1525-142X.2003.03058.x.pd

    Centrosomal kinase Nek2 Cooperates with Oncogenic Pathways to Promote Metastasis

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    Centrosomal kinase Nek2 is overexpressed in different cancers, yet how it contributes toward tumorigenesis remains poorly understood. dNek2 overexpression in a Drosophila melanogaster model led to upregulation of Drosophila Wnt ortholog wingless (Wg), and alteration of cell migration markersβ€”Rho1, Rac1 and E-cadherin (Ecad)β€”resulting in changes in cell shape and tissue morphogenesis. dNek2 overexpression cooperated with receptor tyrosine kinase and mitogen-activated protein kinase signaling to upregulate activated Akt, Diap1, Mmp1 and Wg protein to promote local invasion, distant seeding and metastasis. In tumor cell injection assays, dNek2 cooperated with Ras and Src signaling to promote aggressive colonization of tumors into different adult fly tissues. Inhibition of the PI3K pathway suppressed the cooperation of dNek2 with other growth pathways. Consistent with our fly studies, overexpression of human Nek2 in A549 lung adenocarcinoma and HEK293T cells led to activation of the Akt pathway and increase in b-catenin protein levels. Our computational approach identified a class of Nek2-inhibitory compounds and a novel drug-like pharmacophore that reversed the Nek2 overexpression phenotypes in flies and human cells. Our finding posits a novel role for Nek2 in promoting metastasis in addition to its currently defined role in promoting chromosomal instability. It provides a rationale for the selective advantage of centrosome amplification in cancer

    MicroRNAs and Developmental Robustness: A New Layer Is Revealed

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    MicroRNAs provide a new layer of regulation to ensure that a developmental program of programmed cell death yields a reproducible outcome in spite of perturbations to the system

    Computer Simulation of Cellular Patterning Within the Drosophila Pupal Eye

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    We present a computer simulation and associated experimental validation of assembly of glial-like support cells into the interweaving hexagonal lattice that spans the Drosophila pupal eye. This process of cell movements organizes the ommatidial array into a functional pattern. Unlike earlier simulations that focused on the arrangements of cells within individual ommatidia, here we examine the local movements that lead to large-scale organization of the emerging eye field. Simulations based on our experimental observations of cell adhesion, cell death, and cell movement successfully patterned a tracing of an emerging wild-type pupal eye. Surprisingly, altering cell adhesion had only a mild effect on patterning, contradicting our previous hypothesis that the patterning was primarily the result of preferential adhesion between IRM-class surface proteins. Instead, our simulations highlighted the importance of programmed cell death (PCD) as well as a previously unappreciated variable: the expansion of cells' apical surface areas, which promoted rearrangement of neighboring cells. We tested this prediction experimentally by preventing expansion in the apical area of individual cells: patterning was disrupted in a manner predicted by our simulations. Our work demonstrates the value of combining computer simulation with in vivo experiments to uncover novel mechanisms that are perpetuated throughout the eye field. It also demonstrates the utility of the Glazier–Graner–Hogeweg model (GGH) for modeling the links between local cellular interactions and emergent properties of developing epithelia as well as predicting unanticipated results in vivo

    A personalized platform identifies trametinib plus zoledronate for a patient with KRAS-mutant metastatic colorectal cancer

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    Colorectal cancer remains a leading source of cancer mortality worldwide. Initial response is often followed by emergent resistance that is poorly responsive to targeted therapies, reflecting currently undruggable cancer drivers such as KRAS and overall genomic complexity. Here, we report a novel approach to developing a personalized therapy for a patient with treatment-resistant metastatic KRAS-mutant colorectal cancer. An extensive genomic analysis of the tumor's genomic landscape identified nine key drivers. A transgenic model that altered orthologs of these nine genes in the Drosophila hindgut was developed; a robotics-based screen using this platform identified trametinib plus zoledronate as a candidate treatment combination. Treating the patient led to a significant response: Target and nontarget lesions displayed a strong partial response and remained stable for 11 months. By addressing a disease's genomic complexity, this personalized approach may provide an alternative treatment option for recalcitrant disease such as KRAS-mutant colorectal cancer
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