Das Spätwerk Christoph Martin Wielands und seine Bedeutung für die deutsche Aufklärung /

4. Halberstadter Kolloquium 198

横浜国立大学構内の鳥類目録

application/pdfdepartmental bulletin pape

太陽電他用材料製造プロセスとしてのフラックスを用いた溶融シリコンからのボロン分離法の開発

(エネルギー・環境材料-I)(エネルギー・環境材料)(オーガナイスドセッション9)journal articl

RAPTOR Controls Developmental Growth Transitions by Altering the Hormonal and Metabolic Balance

Vegetative growth requires the systemic coordination of numerous cellular processes, which are controlled by regulatory proteins that monitor extracellular and intracellular cues and translate them into growth decisions. In eukaryotes, one of the central factors regulating growth is the serine/threonine protein kinase Target of Rapamycin (TOR), which forms complexes with regulatory proteins. To understand the function of one such regulatory protein, Regulatory-Associated Protein of TOR 1B (RAPTOR1B), in plants, we analyzed the effect of raptor1b mutations on growth and physiology in Arabidopsis (Arabidopsis thaliana) by detailed phenotyping, metabolomic, lipidomic, and proteomic analyses. Mutation of RAPTOR1B resulted in a strong reduction of TOR kinase activity, leading to massive changes in central carbon and nitrogen metabolism, accumulation of excess starch, and induction of autophagy. These shifts led to a significant reduction of plant growth that occurred nonlinearly during developmental stage transitions. This phenotype was accompanied by changes in cell morphology and tissue anatomy. In contrast to previous studies in rice (Oryza sativa), we found that the Arabidopsis raptor1b mutation did not affect chloroplast development or photosynthetic electron transport efficiency; however, it resulted in decreased CO2 assimilation rate and increased stomatal conductance. The raptor1b mutants also had reduced abscisic acid levels. Surprisingly, abscisic acid feeding experiments resulted in partial complementation of the growth phenotypes, indicating the tight interaction between TOR function and hormone synthesis and signaling in plants.journal articl

ALW-II-41-27, HG-6-63-01 and XMD15-44 chemical structure.

<p>A) Chemical structure of the studied compounds: red colour indicates the “tail”, black colour indicates “linker”, and pink colour indicates the “head” part in the binding. B) Modelling of ALW-II-41-27 (left), XMD15-44 (middle) and HG-6-63-01(right) binding to the DFG-out conformation of RET. C) IC₅₀ dose (nM) of ALW-II-41-27, XMD15-44 and HG-6-63-01 for wt RET, RET/V804L and RET/V804M <i>in vitro</i> kinase activity measured by Invitrogen SelectScreen assay.</p

ALW-II-41-27, XMD15-44 and HG-6-63-01-mediated inhibition of proliferation of RET mutant thyroid carcinoma cell lines.

<p>Top) TT, MZ-CRC-1, TPC1 and Nthy-ori-3-1 cell lines were incubated with vehicle (NT: not treated) or the indicated concentrations of ALW-II-41-27, XMD15-44 and HG-6-63-01 and counted at the indicated time points. Data are the mean ± SD of two experiments performed in triplicate. Bottom) Growth inhibition IC₅₀ of ALW-II-41-27, XMD15-44 and HG-6-63-01 for the different cell lines: 95% CI are indicated in brackets.</p

Inhibition of RET phosphorylation and signaling by ALW-II-41-27, XMD15-44 and HG-6-63-01 in RET mutant thyroid carcinoma cell lines.

<p>Serum-starved human TT (A) and MZ-CRC-1 (B) (MTC), TPC1 (PTC) (C), and non-transformed Nthy-ory-3-1 (NTHY) (D) cell lines were treated for 2 hr with indicated concentrations of ALW-II-41-27, HG-6-63-01 and XMD15-44. 50 μg of total cell lysates were subjected to immunoblotting with αp1062 RET antibodies, phospho-MAPK (αpMAPK) and phospho-SHC (αpSHC) antibodies. The blots were normalized using anti-RET (αRET), anti-MAPK (αMAPK) and anti-SHC (αSHC).</p