126 research outputs found

    Wnt signaling: The Naked truth?

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    Frizzled receptors can activate two alternative signal transduction pathways: the canonical Wnt pathway or the planar cell polarity pathway. Recent studies of the Naked cuticle protein suggest a mechanism for the inactivation of the canonical pathway and concomitant activation of the planar cell polarity pathway

    Wnt signaling: Moving in a new direction

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    Evidence supporting the postulated role of a Wnt ligand in the establishment of planar cell polarity has been elusive, but recent studies show that the movement of epithelial cells during vertebrate gastrulation or Drosophila dorsal closure depends on both a Wnt ligand and the planar cell polarity pathway

    Wnt signaling: Moving in a new direction

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    Evidence supporting the postulated role of a Wnt ligand in the establishment of planar cell polarity has been elusive, but recent studies show that the movement of epithelial cells during vertebrate gastrulation or Drosophila dorsal closure depends on both a Wnt ligand and the planar cell polarity pathway

    Synthesis of Aliphatic Bis(Thioureas)

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    The synthesis of aliphatic bifunctional thioureas have been attempted using several nucleophilic displacement reactions. The first method involved treatment of an aliphatic diamine with ammonium thiocyanate, under two different sets of reaction conditions. The first set of reaction conditions utilized water as the solvent, while second employed acetone as the solvent. Both of the reactions utilizing l,2-ethylenediamine and ammonium thiocyanate did not afford the desired bis(thioureas). In particular, the crystalline solid obtained from the reaction carried out in water was 57.8 ± 0.05 % thiocyanate by mass. The second nucleophilic addition method involved the treatment of both 1,2-ethylenediamine and 1,6-hexanediamine diamine with silicon tetraisothiocyanate in anhydrous benzene. The product from the reaction of l,6-hexanediamine with silicon tetraisothiocyanate in anhydrous benzene was found to be 40.3 ± 2.07 % thiocyanate by mass. The third set of reaction conditions involved treatment of 1,6hexanediamine with silver thiocyanate in concentrated ammonium hydroxide. As a result of the presence characteristic thiocyanate IR absorbance peak at 2100 cm-1 in the product, it was found to contain thiocyanate ions. It was concluded that the product was composed of mainly the 1,6 hexanediamine thiocyanate salts. The final set of reaction conditions involved treatment of 1,6hexanediamine with silver thiocyanate and thiourea, in concentrated ammonium hydroxide. Upon analysis of the resulting reaction mixtures, it was determined that each fraction contained no thiocyanate anion or starting thiourea. Further work needs to be carried out in order to determine the products

    Real-time monitor of geomagnetic field in the near-pole regions as an index of magnetospheric electric field

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    Solar wind electric field that penetrates into the magnetosphere is an important key for causes of magnetosphenc disturbances. Since PC index, produced from the variation of the magnetic field in the near-pole regions is known to be a good indicator of magnetospheric electric field, monitoring the magnetic activity in the near-pole regions in real-time is useful for nowcasting/forecasting space weather. From the comparison of horizontal components of the magnetic field data between two stations, Eureka and Thule, it is found that the correlation between these two stations are quite high except for the summer months. This result suggests that magnetic field variations in the near-pole region are uniform, and the index can be produced throughout the year using magnetic field data in the northern and southern near-pole region

    Puckered, a Drosophila MAPK phosphatase, ensures cell viability by antagonizing JNK-induced apoptosis

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    MAPK phosphatases (MKPs) are important negative regulators of MAPKs in vivo, but ascertaining the role of specific MKPs is hindered by functional redundancy in vertebrates. Thus, we characterized MKP function by examining the function of Puckered (Puc), the sol

    A screen for mutations that suppress the phenotype of Drosophila armadillo, the beta-catenin homolog.

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    During development signaling pathways coordinate cell fates and regulate the choice between cell survival or programmed cell death. The well-conserved Wingless/Wnt pathway is required for many developmental decisions in all animals. One transducer of the Wingless/Wnt signal is Armadillo/beta-catenin. Drosophila Armadillo not only transduces Wingless signal, but also acts in cell-cell adhesion via its role in the epithelial adherens junction. While many components of both the Wingless/Wnt signaling pathway and adherens junctions are known, both processes are complex, suggesting that unknown components influence signaling and junctions. We carried out a genetic modifier screen to identify some of these components by screening for mutations that can suppress the armadillo mutant phenotype. We identified 12 regions of the genome that have this property. From these regions and from additional candidate genes tested we identified four genes that suppress arm: dTCF, puckered, head involution defective (hid), and Dpresenilin. We further investigated the interaction with hid, a known regulator of programmed cell death. Our data suggest that Wg signaling modulates Hid activity and that Hid regulates programmed cell death in a dose-sensitive fashion

    Positional Cloning of a Type 2 Diabetes Quantitative Trait Locus; Tomosyn-2, a Negative Regulator of Insulin Secretion

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    We previously mapped a type 2 diabetes (T2D) locus on chromosome 16 (Chr 16) in an F2 intercross from the BTBR T (+) tf (BTBR) Lepob/ob and C57BL/6 (B6) Lepob/ob mouse strains. Introgression of BTBR Chr 16 into B6 mice resulted in a consomic mouse with reduced fasting plasma insulin and elevated glucose levels. We derived a panel of sub-congenic mice and narrowed the diabetes susceptibility locus to a 1.6 Mb region. Introgression of this 1.6 Mb fragment of the BTBR Chr 16 into lean B6 mice (B6.16BT36–38) replicated the phenotypes of the consomic mice. Pancreatic islets from the B6.16BT36–38 mice were defective in the second phase of the insulin secretion, suggesting that the 1.6 Mb region encodes a regulator of insulin secretion. Within this region, syntaxin-binding protein 5-like (Stxbp5l) or tomosyn-2 was the only gene with an expression difference and a non-synonymous coding single nucleotide polymorphism (SNP) between the B6 and BTBR alleles. Overexpression of the b-tomosyn-2 isoform in the pancreatic β-cell line, INS1 (832/13), resulted in an inhibition of insulin secretion in response to 3 mM 8-bromo cAMP at 7 mM glucose. In vitro binding experiments showed that tomosyn-2 binds recombinant syntaxin-1A and syntaxin-4, key proteins that are involved in insulin secretion via formation of the SNARE complex. The B6 form of tomosyn-2 is more susceptible to proteasomal degradation than the BTBR form, establishing a functional role for the coding SNP in tomosyn-2. We conclude that tomosyn-2 is the major gene responsible for the T2D Chr 16 quantitative trait locus (QTL) we mapped in our mouse cross. Our findings suggest that tomosyn-2 is a key negative regulator of insulin secretion
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