Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism

Recent studies suggest that cardiac fibroblast-specific p38α MAPK contributes to the development of cardiac hypertrophy, but the underlying mechanism is unknown. Our study used a novel fibroblast-specific, tamoxifen-inducible p38α knockout (KO) mouse line to characterize the role of fibroblast p38α in modulating cardiac hypertrophy, and we elucidated the mechanism. Myocardial injury was induced in tamoxifen-treated Cre-positive p38α KO mice or control littermates via chronic infusion of the β-adrenergic receptor agonist isoproterenol. Cardiac function was assessed by pressure-volume conductance catheter analysis and was evaluated for cardiac hypertrophy at tissue, cellular, and molecular levels. Isoproterenol infusion in control mice promoted overt cardiac hypertrophy and dysfunction (reduced ejection fraction, increased end systolic volume, increased cardiac weight index, increased cardiomyocyte area, increased fibrosis, and up-regulation of myocyte fetal genes and hypertrophy-associated microRNAs). Fibroblast-specific p38α KO mice exhibited marked protection against myocardial injury, with isoproterenol-induced alterations in cardiac function, histology, and molecular markers all being attenuated. In vitro mechanistic studies determined that cardiac fibroblasts responded to damaged myocardium by secreting several paracrine factors known to induce cardiomyocyte hypertrophy, including IL-6, whose secretion was dependent upon p38α activity. In conclusion, cardiac fibroblast p38α contributes to cardiomyocyte hypertrophy and cardiac dysfunction, potentially via a mechanism involving paracrine fibroblast-to-myocyte IL-6 signaling.-Bageghni, S. A., Hemmings, K. E., Zava, N., Denton, C. P., Porter, K. E., Ainscough, J. F. X., Drinkhill, M. J., Turner, N. A. Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism

Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism

Recent studies suggest that cardiac fibroblast-specific p38α MAPK contributes to the development of cardiac hypertrophy, but the underlying mechanism is unknown. Our study used a novel fibroblast-specific, tamoxifen-inducible p38α knockout (KO) mouse line to characterize the role of fibroblast p38α in modulating cardiac hypertrophy, and we elucidated the mechanism. Myocardial injury was induced in tamoxifen-treated Cre-positive p38α KO mice or control littermates via chronic infusion of the β-adrenergic receptor agonist isoproterenol. Cardiac function was assessed by pressure–volume conductance catheter analysis and was evaluated for cardiac hypertrophy at tissue, cellular, and molecular levels. Isoproterenol infusion in control mice promoted overt cardiac hypertrophy and dysfunction (reduced ejection fraction, increased end systolic volume, increased cardiac weight index, increased cardiomyocyte area, increased fibrosis, and up-regulation of myocyte fetal genes and hypertrophy-associated microRNAs). Fibroblast-specific p38α KO mice exhibited marked protection against myocardial injury, with isoproterenol-induced alterations in cardiac function, histology, and molecular markers all being attenuated. In vitro mechanistic studies determined that cardiac fibroblasts responded to damaged myocardium by secreting several paracrine factors known to induce cardiomyocyte hypertrophy, including IL-6, whose secretion was dependent upon p38α activity. In conclusion, cardiac fibroblast p38α contributes to cardiomyocyte hypertrophy and cardiac dysfunction, potentially via a mechanism involving paracrine fibroblast-to-myocyte IL-6 signaling.—Bageghni, S. A., Hemmings, K. E., Zava, N., Denton, C. P., Porter, K. E., Ainscough, J. F. X., Drinkhill, M. J., Turner, N. A. Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism

The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory

The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-de-pendent nuclear matrix. CIZ1 is recruited to Xi in response to expression of X inactive-specific transcript (Xist) RNA during the earliest stages of X inactivation in embryonic stem cells and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E repeats of Xist. CIZ1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder. Interestingly, in mouse embryonic fibroblast cells derived from CIZ1-null embryos, Xist RNA localization is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localization is reinstated following re-expression of CIZ1. Focal localization of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1-null animals, suggesting a possible explanation for female-specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages

Asenne 2014 -mallisto : Kaupallistaminen mallistosuunnittelussa

Opinnäytetyön tavoitteena oli suunnitella Asia Promo -yrityksen Asenne-brändille 2014 miestenvaatemallisto. Mallisto julkaistaan kerran vuodessa ja se myydään kesämallistojen ajankohtana. Malliston tavoite on toteuttaa ensisijaisesti kevät-kesä-sesongin kysyntä, mutta sen tulisi olla ajankohtainen myös syksy-talvi-sesongilla. Toisena tavoitteena on tutkia brändin asemaa ja kaupallisuuden vahvistamiskeinoja suunnittelun avulla. Tutkimus toteutettiin tapaustutkimuksena. Kaupallistamiskeinoja tutkittiin sisäisen ja ulkoisen benchmarkingin avulla. Sisäisessä benchmarkingissa tutkittiin vuosien 2012 ja 2013 mallistojen kaupallista menestymistä tuotteittain. Ulkoisessa benchmarkingissa Asenne-brändiä vertailtiin samantyyppisiin kansainvälisiin brändeihin. Vertailututkimuksen jälkeen tutkittiin suunnitteluprosessia kaupallistamiskeinojen näkökulmasta. Trendiennusteita, kaupallista suunnittelua, brändäyksen keinoja sekä cool huntingia käytettiin tapoina havaita ja kerätä tietoa. Myös edellisten mallistojen kokemukset olivat tärkeitä lähteitä suunnitteluprosessissa. Läpikäytäviä aiheita ovat tiedonkeruu, malliston koko, teema, väri- ja materiaalivalinnat sekä tuotteet. Opinnäytetyön tuloksena syntyi mallisto, joka on kaupallisesti kilpailukykyinen kuvaten Asenne-brändin imagoa sekä tietopaketti kaupallisuuden lisäämistä koskevista keinoista yrityksen tarpeeseen. Opinnäytetyön päätavoitteen toteuttanut mallisto valmistui aikataulussa ja siitä ryhdytään valmistuttamaan mallikappaleita sekä myyntimallistoa. Opinnäytetyö sisältää teemakuvauksen, moodboardin, mallisto- ja värikartan.The primary objective for this thesis is to create a commercial collection for Asia Promo Ltd under its in house brand Asenne. The collection is published once a year and it is sold during the sales of spring-summer collections. Asenne collection should primarily meet to the need of the spring-summer season, but it should also be current during the autumn-winter season. The second objective for the thesis is to study the position of Asenne as a brand and the means to reinforce the commercial aspects through design. Firstly, the study was conducted as a case study. The commercial aspects were studied by both internal and external benchmarking. The commercial success of the 2012 and 2013 collections were studied in the internal benchmarking. Simultaneously, in external benchmarking, Asenne was studied against international niche surf brands. Moreover, after benchmarking, the research is focused on the design process specializing in commercialism. Trend forecasts, commercial design, branding and cool hunting were used to gather information for the collection’s design. Also experiences with the previous collections were important sources to study the design process. Altogether, matters discussed were information gathering, collection size, theme, products and, color and material choices. As the result of the thesis, the Asenne collection 2014 was born. It reflects the brand image and is commercially competitive. The information package as a means to increase commercial aspects in design was also created for the needs of the company. The collection met its deadline and next step is to produce the prototypes and the sales catalogue. In addition, the thesis includes collection sheet, color palette, theme information and mood board.The primary objective for this thesis is to create a commercial collection for Asia Promo Ltd under its in house brand Asenne. The collection is published once a year and it is sold during the sales of spring-summer collections. Asenne collection should primarily meet to the need of the spring-summer season, but it should also be current during the autumn-winter season. The second objective for the thesis is to study the position of Asenne as a brand and the means to reinforce the commercial aspects through design. Firstly, the study was conducted as a case study. The commercial aspects were studied by both internal and external benchmarking. The commercial success of the 2012 and 2013 collections were studied in the internal benchmarking. Simultaneously, in external benchmarking, Asenne was studied against international niche surf brands. Moreover, after benchmarking, the research is focused on the design process specializing in commercialism. Trend forecasts, commercial design, branding and cool hunting were used to gather information for the collection’s design. Also experiences with the previous collections were important sources to study the design process. Altogether, matters discussed were information gathering, collection size, theme, products and, color and material choices. As the result of the thesis, the Asenne collection 2014 was born. It reflects the brand image and is commercially competitive. The information package as a means to increase commercial aspects in design was also created for the needs of the company. The collection met its deadline and next step is to produce the prototypes and the sales catalogue. In addition, the thesis includes collection sheet, color palette, theme information and mood board

Ta'assub-Fanaticism

It has been hypothesized that interleukin-1alpha (IL-1α) is released from damaged cardiomyocytes following myocardial infarction (MI) and activates cardiac fibroblasts via its receptor (IL-1R1) to drive the early stages of cardiac remodeling. This study aimed to definitively test this hypothesis using cell type-specific IL-1α and IL-1R1 knockout (KO) mouse models. A floxed Il1α mouse was created and used to generate a cardiomyocyte-specific IL-1α KO mouse line (MIL1AKO). A tamoxifen-inducible fibroblast-specific IL-1R1 hemizygous KO mouse line (FIL1R1KO) was also generated. Mice underwent experimental MI (permanent left anterior descending coronary artery ligation) and cardiac function was determined 4 weeks later by conductance pressure-volume catheter analysis. Molecular markers of remodeling were evaluated at various time points by real-time RT-PCR and histology. MIL1AKO mice showed no difference in cardiac function or molecular markers of remodeling post-MI compared with littermate controls. In contrast, FIL1R1KO mice showed improved cardiac function and reduced remodeling markers post-MI compared with littermate controls. In conclusion, these data highlight a key role for the IL-1R1/cardiac fibroblast signaling axis in regulating post-MI remodeling and provide support for the continued development of anti-IL-1 therapies for improving cardiac function after MI. Cardiomyocyte-derived IL-1α was not an important contributor to post-MI remodeling in this mode

The nuclear matrix protein CIZ1 facilitates localisation of Xist RNA to the inactive X-chromosome territory

The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins, and has been linked with adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells, and is retained by interaction with the RNAdependent nuclear matrix. CIZ1 is recruited to Xi in response to expression of Xist RNA during the earliest stages of X-inactivation in embryonic stem cells, and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E-repeats of Xist. CIZ1 null mice, although viable, display fully penetrant female specific lymphoproliferative disorder. Interestingly, in MEF cells derived from CIZ1 null embryos Xist RNA localisation is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localisation is reinstated following re-expression of CIZ1. Focal localisation of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1 null animals, suggesting a possible explanation for female specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages