Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid synovial fibroblasts

Rho is a major small GTP-binding protein that is involved in the regulation of various cell functions, including proliferation and cell migration, through activation of multiple signaling molecules in various types of cells. We studied its roles in synovial fibroblasts (SFs) in patients with rheumatoid arthritis (RA) and clarified its relevance to RA synovitis, with the following results. 1)We found that the thrombin receptor was overexpressed on RA synovial fibroblasts (RA SFs) and that thrombin induced a marked proliferation and progression of the cell cycle to the S phase in these cells. 2)We also found that thrombin efficiently activated Rho. 3)Rho activation and proliferation and the progression of the cell cycle to the S phase were completely blocked by p115RGS (an N-terminal regulator of the G-protein signaling domain of p115RhoGEF) and by the C-terminal fragments of Gα13 (an inhibitor of the interaction of receptors with G13). 4)Thrombin induced the secretion of IL-6 by RA SFs, but this action was blocked by p115RGS or Gα13. Our findings show that the actions of thrombin on the proliferation of RA SFs, cell-cycle progression to the S phase, and IL-6 secretion were mainly mediated by the G13 and RhoGEF pathways. These results suggest that p115RGS and Gα13 could be potent inhibitors of such functions. A rational design of future therapeutic strategies for RA synovitis could perhaps include the exploitation of the Rho pathway to directly reduce the growth of synovial cells

Genome-Wide Expression of Azoospermia Testes Demonstrates a Specific Profile and Implicates ART3 in Genetic Susceptibility

Infertility affects about one in six couples attempting pregnancy, with the man responsible in approximately half of the cases. Because the pathophysiology underlying azoospermia is not elucidated, most male infertility is diagnosed as idiopathic. Genome-wide gene expression analyses with microarray on testis specimens from 47 non-obstructive azoospermia (NOA) and 11 obstructive azoospermia (OA) patients were performed, and 2,611 transcripts that preferentially included genes relevant to gametogenesis and reproduction according to Gene Ontology classification were found to be differentially expressed. Using a set of 945 of the 2,611 transcripts without missing data, NOA was further categorized into three classes using the non-negative matrix factorization method. Two of the three subclasses were different from the OA group in Johnsen's score, FSH level, and/or LH level, while there were no significant differences between the other subclass and the OA group. In addition, the 52 genes showing high statistical difference between NOA subclasses (p < 0.01 with Tukey's post hoc test) were subjected to allelic association analyses to identify genetic susceptibilities. After two rounds of screening, SNPs of the ADP-ribosyltransferase 3 gene (ART3) were associated with NOA with highest significance with ART3-SNP25 (rs6836703; p = 0.0025) in 442 NOA patients and 475 fertile men. Haplotypes with five SNPs were constructed, and the most common haplotype was found to be under-represented in patients (NOA 26.6% versus control 35.3%, p = 0.000073). Individuals having the most common haplotype showed an elevated level of testosterone, suggesting a protective effect of the haplotype on spermatogenesis. Thus, genome-wide gene expression analyses were used to identify genes involved in the pathogenesis of NOA, and ART3 was subsequently identified as a susceptibility gene for NOA. These findings clarify the molecular pathophysiology of NOA and suggest a novel therapeutic target in the treatment of NOA

Cut loci and conjugate loci on Liouville surfaces

In the earlier paper (Itoh and Kiyohara, Manuscr Math 114:247–264, 2004), we showed that the cut locus of a general point on two-dimensional ellipsoid is a segment of a curvature line and proved "Jacobi’s last geometric statement" on the singularities of the conjugate locus. In the present paper,we showthat a wider class of Liouville surfaces possess such simple cut loci and conjugate loci. The results include the determination of cut loci and the set of poles on two-sheeted hyperboloids and elliptic paraboloids

Konfigurering och ibruktagning av KNX system

Detta examensarbete behandlar grunderna i KNX samt programmering av KNX enheter med datorprogrammet ETS 4. I arbetet beskrivs hur KNX systemet fungerar, hur det är uppbyggt och de olika överföringsmedium som kan användas då KNX enheter kommunicerar. Jag beskriver också hur ETS 4 installeras på datorn och hur man kommer igång med programmeringen av KNX enheterna. Inför detta examensarbete har jag studerat en del av ABB:s KNX enheter samt deras funktioner och konfigurationsmöjligheter. Syftet med detta examensarbete är att skapa en liten handbok för hur ett KNX system är uppbyggt samt hur KNX enheterna programmeras med ETS 4.Tämä opinnäytetyö käsittelee KNX:n perusteita ja KNX-laitteiden ohjelmointia ETS 4 tietokoneohjelman avulla. Työssä kuvaillaan, miten KNX-järjestelmä toimii, millä tavalla se on rakennettu sekä mitä eri siirtomedioita voidaan käyttää KNX-laitteiden viestinnässä. Työssä kuvaillaan myös, miten ETS-ohjelma asennetaan tietokoneella ja miten päästään aloittamaan KNX-laitteiden ohjelmointi. Ennen tätä opinnäytetyötä kirjoittaja on opiskellut ABB:n KNX-laitteita sekä niiden toimintoja ja konfiguraatiomahdollisuuksia. Opinnäytetyön tarkoituksena on tehdä pieni käsikirja, joka kertoo, miten KNX- järjestelmä on rakennettu sekä millä tavalla KNX-laitteet ohjelmoidaan ETS 4:llä.In this thesis I deal with the basics of KNX as well as the programming of KNX devices with the computer software ETS 4. In the thesis I describe how the KNX system works, how it is built and the different communication media that are used for communication between KNX devices. I also describe how ETS 4 is installed on a personal computer and how to get started with the programming of the KNX devices. When preparing for this thesis I studied a part of ABB’s KNX devices, their functions as well as their configuration possibilities. The purpose of this thesis is to create a small manual that can be used to see how a KNX system is built and to check how KNX devices are programmed with ETS 4