STATc is a key regulator of the transcriptional response to hyperosmotic shock

<p>Abstract</p> <p>Background</p> <p><it>Dictyostelium discoideum </it>is frequently subjected to environmental changes in its natural habitat, the forest soil. In order to survive, the organism had to develop effective mechanisms to sense and respond to such changes. When cells are faced with a hypertonic environment a complex response is triggered. It starts with signal sensing and transduction and leads to changes in cell shape, the cytoskeleton, transport processes, metabolism and gene expression. Certain aspects of the <it>Dictyostelium </it>osmotic stress response have been elucidated, however, no comprehensive picture was available up to now.</p> <p>Results</p> <p>To better understand the <it>D. discoideum </it>response to hyperosmotic conditions, we performed gene expression profiling using DNA microarrays. The transcriptional profile of cells treated with 200 mM sorbitol during a 2-hour time course revealed a time-dependent induction or repression of 809 genes, more than 15% of the genes on the array, which peaked 45 to 60 minutes after the hyperosmotic shock. The differentially regulated genes were applied to cluster analysis and functional annotation using gene GO terms. Two main responses appear to be the down-regulation of the metabolic machinery and the up-regulation of the stress response system, including STATc. Further analysis of STATc revealed that it is a key regulator of the transcriptional response to hyperosmotic shock. Approximately 20% of the differentially regulated genes were dependent on the presence of STATc.</p> <p>Conclusion</p> <p>At least two signalling pathways are activated in <it>Dictyostelium </it>cells subjected to hypertonicity. STATc is responsible for the transcriptional changes of one of them.</p

Profilin isoforms in Dictyostelium discoideum

AbstractEukaryotic cells contain a large number of actin binding proteins of different functions, locations and concentrations. They bind either to monomeric actin (G-actin) or to actin filaments (F-actin) and thus regulate the dynamic rearrangement of the actin cytoskeleton. The Dictyostelium discoideum genome harbors representatives of all G-actin binding proteins including actobindin, twinfilin, and profilin. A phylogenetic analysis of all profilins suggests that two distinguishable groups emerged very early in evolution and comprise either vertebrate and viral profilins or profilins from all other organisms. The newly discovered profilin III isoform in D. discoideum shows all functions that are typical for a profilin. However, the concentration of the third isoform in wild type cells reaches only about 0.5% of total profilin. In a yeast-2-hybrid assay profilin III was found to bind specifically to the proline-rich region of the cytoskeleton-associated vasodilator-stimulated phosphoprotein (VASP). Immunolocalization studies showed similar to VASP the profilin III isoform in filopodia and an enrichment at their tips. Cells lacking the profilin III isoform show defects in cell motility during chemotaxis. The low abundance and the specific interaction with VASP argue against a significant actin sequestering function of the profilin III isoform

Lgl2 Executes Its Function as a Tumor Suppressor by Regulating ErbB Signaling in the Zebrafish Epidermis

Changes in tissue homeostasis, acquisition of invasive cell characteristics, and tumor formation can often be linked to the loss of epithelial cell polarity. In carcinogenesis, the grade of neoplasia correlates with impaired cell polarity. In Drosophila, lethal giant larvae (lgl), discs large (dlg), and scribble, which are components of the epithelial apico-basal cell polarity machinery, act as tumor suppressors, and orthologs of this evolutionary conserved pathway are lost in human carcinoma with high frequency. However, a mechanistic link between neoplasia and vertebrate orthologs of these tumor-suppressor genes remains to be fully explored at the organismal level. Here, we show that the pen/lgl2 mutant phenotype shares two key cellular and molecular features of mammalian malignancy: cell autonomous epidermal neoplasia and epithelial-to-mesenchymal-transition (EMT) of basal epidermal cells including the differential expression of several regulators of EMT. Further, we found that epidermal neoplasia and EMT in pen/lgl2 mutant epidermal cells is promoted by ErbB signalling, a pathway of high significance in human carcinomas. Intriguingly, EMT in the pen/lgl2 mutant is facilitated specifically by ErbB2 mediated E-cadherin mislocalization and not via canonical snail–dependent down-regulation of E-cadherin expression. Our data reveal that pen/lgl2 functions as a tumor suppressor gene in vertebrates, establishing zebrafish pen/lgl2 mutants as a valuable cancer model

STATc is a key regulator of the transcriptional response to hyperosmotic shock-2

<p><b>Copyright information:</b></p><p>Taken from "STATc is a key regulator of the transcriptional response to hyperosmotic shock"</p><p>http://www.biomedcentral.com/1471-2164/8/123</p><p>BMC Genomics 2007;8():123-123.</p><p>Published online 21 May 2007</p><p>PMCID:PMC1888708.</p><p></p>1.5 fold in the time course of sorbitol treatment was clustered with GeneSpring 7.2. Four major clusters (1–4) can be distinguished. The dendrogram is displayed on the left. The differentially regulated genes are depicted as coloured lines and the time of treatment in minutes is shown at the bottom. The colour represents the fold induction (red) or repression (blue) as shown in the colour scale below the figure. Non-regulated genes are displayed in yellow. (B) A selection of the GO biological process terms that were enriched in each of the clusters is presented. GO tree levels are shown on the left. Bar lengths represent the fold enrichment (scale x-axis). The table indicates the number of genes with a particular annotation in the cluster (List), on the entire array (Total), the significance for enrichment (P-value) and the annotation. (C) Expression profiles of selected genes from each cluster. The following abbreviations for differentially regulated genes are used. Cluster 1: A, A; B6, 20S proteasome subunit beta-6; C4, 26S proteasome subunit ATPase 4; 11, 26S proteasome non-ATPase regulatory subunit 11; 2, 26S proteasome regulatory subunit 2; C, Cysteine Protease Inhibitor; A, cysteine proteinase 1. Cluster 2: A, coronin; B, actin related protein 2; B, profilin II; A, NCK-Associated Protein; C, actin binding protein; act8, actin8. Cluster 3: C, STATc; A, RasGTPase-activating protein; A, Severin kinase; G21, ABC transporter G family protein. Cluster 4: , vacuolar H+-ATPase subunit

STATc is a key regulator of the transcriptional response to hyperosmotic shock-3

<p><b>Copyright information:</b></p><p>Taken from "STATc is a key regulator of the transcriptional response to hyperosmotic shock"</p><p>http://www.biomedcentral.com/1471-2164/8/123</p><p>BMC Genomics 2007;8():123-123.</p><p>Published online 21 May 2007</p><p>PMCID:PMC1888708.</p><p></p> if STATc is not involved in the transcriptional regulation. (B) Expected overlap in experiments I and II if STATc is the only transcriptional regulator in response to hypertonicity. (C) Venn diagram of the observed differentially regulated genes from the three comparisons: wt cells treated versus untreated (I), RIC cells treated versus STATctreated (II) and STATctreated versus untreated (III). The numbers of up- and down-regulated genes of the single experiments are printed in red and green, respectively. Genes shared between 2 or 3 comparisons (shaded region) were applied to further analysis

STATc is a key regulator of the transcriptional response to hyperosmotic shock-1

<p><b>Copyright information:</b></p><p>Taken from "STATc is a key regulator of the transcriptional response to hyperosmotic shock"</p><p>http://www.biomedcentral.com/1471-2164/8/123</p><p>BMC Genomics 2007;8():123-123.</p><p>Published online 21 May 2007</p><p>PMCID:PMC1888708.</p><p></p>ts. The data are expressed as means of fold change ± SD of three independent experiments. The corresponding DDB IDs from left to right as follows: DDB0188166, DDB0235172, DDB0188166, DDB0190245, DDB0185120

STATc is a key regulator of the transcriptional response to hyperosmotic shock-4

<p><b>Copyright information:</b></p><p>Taken from "STATc is a key regulator of the transcriptional response to hyperosmotic shock"</p><p>http://www.biomedcentral.com/1471-2164/8/123</p><p>BMC Genomics 2007;8():123-123.</p><p>Published online 21 May 2007</p><p>PMCID:PMC1888708.</p><p></p>ters (1–8) can be distinguished of which clusters 4 and 7 contain those genes that are solely regulated by STATc. The dendrogram is displayed on the left. The differentially regulated genes are depicted as coloured lines. The colour represents the fold of induction (red) or repression (blue) (colour scale see Fig. 3). Non-regulated genes are displayed in yellow. OP1: Osmostress induced pathway 1; OSP: Osmostress induced STATc pathway; SP: STATc pathway irrespective of osmostress. (B) GO biological process terms enriched in cluster 4 and 7. GO tree levels are shown on the left. Bar lengths represent the fold enrichment (scale x-axis). The table indicates the number of genes with a particular annotation in the cluster (List), on the entire array (Total), the significance for enrichment (P-value) and the annotation

Media Pembelajaran Interaktif Berbasis Video Dalam Penggunaan Scan Tool Tipe Launch Thinkdiag Easydiag 4.0

Penelitian ini memiliki tujuan untuk memudahkan para peserta didik dalam memahami penggunaan scan tool khususnya scan tool tipe launch thinkdiag easydiag 4.0. Guna meningkatkan kualitas pembelajaran di jurusan Teknik Mesin Otomotif, maka diperlukan media pembelajaran yang lebih interaktif. Pada proyek akhir ini, metode yang digunakan adalah metode kuantitatif. Sedangkan untuk sumber data yang diperoleh berdasarkan penyebaran informasi berupa kuesioner yang ditujukan kepada para peserta didik yang telah menggunakan media interaktif saat pembelajaran. Berdasarkan pengujian dari proyek akhir ini, menghasilkan nilai sebesar 56,7% dari jumlah responden mahasiswa. Sehingga peserta didik dapat dengan mudah memahami materi penggunaan scan tool tipe launch thinkdiag easydiag 4.0 berkat media pembelajaran interaktif.This study aims to make it easier for students to understand the use of scan tools, especially the Thinkdiag Easydiag 4.0 launch type scan tool. In order to improve the quality of learning in the Automotive Mechanical Engineering department, more interactive learning media are need-ed. In this final project, the method used is a quantitative method. As for the source of the data obtained based on the dissemination of information in the form of a questionnaire addressed to students who have used interactive media during learning. Based on the testing of this final pro-ject, it resulted in a score of 56.7% of the total student respondents. So that students can easily understand the material for using the Thinkdiag Easydiag 4.0 launch type scan tool thanks to interactive learning media