TMPRSS4 is expressed by epithelial and mast cells in bleomycin-induced pulmonary fibrosis.

<p>Representative photomicrographs of immunohistochemical staining performed with antibody against TMPRSS4 in lung tissue sections from WT mice injured with bleomycin. The immunoreactive enzyme was observed in epithelial (panel A, black arrow) and interstitial cells (panels B and C black arrows). Panel D: no positive staining was detected in normal lungs. Panel E: shows the negative control where the specific antibody was omitted. All sections were counterstained with hematoxylin. Panels F-I: Representative images of immunofluorescence staining performed with specific antibodies against TMPRSS4 and tryptase; Tissues were stained for TMPRSS4 (Dylight-549, red) and tryptase (AF-488, green). The colocalization of TMPRSS4 and tryptase was determined by fluorescence microscopy and images were merged to resolve the co-localization of these proteins.</p

Immunolocalization of TMPRSS4 in IPF and control lungs.

<p>Representative photomicrographs of immunohistochemical staining performed with antibody against TMPRSS4 in lung tissue sections. Strong staining was observed in epithelial (panels A and B) and interstitial cells (panel C) in IPF lungs (n = 5), whereas no positive labeling was detected in normal lungs (n = 3) (panel D). Panel E shows the negative control where the specific antibody was omitted. All sections were counterstained with hematoxylin. Arrows indicate positive cells.</p

TMPRSS4 deficiency reduces bleomycin-induced collagen deposition in lungs.

<p>Wild type (WT), TMPRSS4 deficient (KO) and haplodeficient (HT) mice were instilled with Bleomycin (7 U/Kg) and studied at 28 days. Collagen content was quantified by hydroxyproline assay. Data are expressed as mean ± SD of 7–12 animals per group. *<i>P</i>< 0.01 compared with WT instilled animals.</p

TMPRSS4 increases E-cadherin expression.

<p>Human alveolar epithelial cells (A549) were stimulated with TMPRSS4 (100 ng/mL) or TGF-β1 (5 ng/mL) and the expression of E-cadherin and α-SMA was determined by quantitative RT-PCR and Western blot. Panel A and C: At 4 days, TMPRSS4 significantly increased the level of E-cadherin mRNA and reduced α-SMA mRNA compared with control sample (*p <0.01). Data were normalized to the level of 18S rRNA. Panel B and D: Total protein from stimulated cells was extracted and western blot analysis performed with specific antibodies for E-cadherin and α-SMA. TGF-β1 was used as a positive control for EMT. Panel E: Rat (RLE-6TN) alveolar epithelial cells were stimulated with TMPRSS4 (100 ng/mL) or TGF-β1 (5ng/mL) for 4 days. Westerns are representative of three independent experiments. Panel F: Western blot analysis of control A549 epithelial cells and A549 stimulated with TGFβ1, TMPRSS4 or TGFβ1 plus TMPRSS4.</p

TMPRSS4 is expressed by alveolar and bronchial epithelial cells.

<p>Panel A: Gene levels of TMPRSS4 were quantified by real-time RT-PCR in A549 and HBE4-E6/E7 epithelial cells and in normal (n = 3) and IPF lung fibroblasts (n = 3). Expression was observed in both epithelial cell lines while no expression was found in fibroblasts. Panel B: Protein expression of TMPRSS4 (48 KDa) was confirmed by western blot in both epithelial cell lines. Panel C: Representative Western blot of TMPRSS4 in normal and IPF lung fibroblasts. A549 epithelial cells were used as positive control. Panel D: Western blot of A549 epithelial cells stimulated with TGFβ1 for 96 hours.</p

TMPRSS4 deficiency attenuates bleomycin-induced lung damage in mice.

<p>Wild type (WT), TMPRSS4 deficient (KO) and haplodeficient (HT) mice were instilled intratracheally with bleomycin (7 U/Kg) or saline solution and studied at 28 days. Panel A: control mice instilled with saline solution. Panel B: mice with bleomycin-induced pulmonary fibrosis. Histopathologic analysis was performed using hematoxylin and Masson trichrome staining.</p

TMPRSS4 reduces alveolar epithelial growth rate.

<p>Panel A: Human alveolar epithelial cells (A549) were cultured in 48-well culture plates in medium without FBS and stimulated with TMPRSS4 (0.1, 1, 10 and 100 ng/mL). Panel B: The analysis was repeated with 100 ng/ml in two independent experiments. Cell numbers were estimated by WST-1 assay at 4 days of culture. Each point represents means ± SD of one representative experiment performed in triplicate. *P < 0.05.</p

TMPRSS4 is upregulated in idiopathic pulmonary fibrosis (IPF) lungs.

<p>Gene expression of TMPRSS4 was quantified by real-time PCR in total RNA obtained from IPF (n = 7), hypersensitivity pneumonitis (HP) (n = 6) and normal lungs (n = 4). Strong upregulation was observed in IPF tissues compared with HP and control lungs. Data are expressed as means ± SD of copy number normalized to 18S rRNA; * p<0.05, IPF versus control and HP.</p

Additional file 3: of A transcriptome-based model of central memory CD4 T cell death in HIV infection

RMA-normalized gene expression of differentiation-related genes. Table that lists differentiation-related genes and their normalized expression values in each CD4 T cell subpopulation sample. (XLS 631 kb

MALEREI, BÖSE (PAINTING, EVIL)

There is hardly any other art genre as heavily confronted with contradictions, prejudices and clichés as painting. Year after year, its end is proclaimed, while every three years its new energy is celebrated, and in the midst of all discussions, paintings achieve record-breaking prices at international art fairs and auctions, as if nothing ever happened. It seems like painting has become an anachronism of itself. In our fast moving and accumulative world, painting positions itself diametrically, for its process of updating requires long periods of time, dialogues with history, and feedback loops. With the exhibition Malerei, böse (Painting, evil), the Kunstverein in Hamburg initiates a critical debate on painting’s subversive potential. The exhibition focuses on artworks using the medium’s manifold inscriptions to challenge aesthetical and moral concepts, using exaggeration, overload, kitsch, irony and violence, as well as a playful treatment of preconceptions. At first appearance these paintings may seem enticing, but on second sight they reveal an abyss. Some in large scale, others hardly bigger than a sheet of paper, either playful or serious, they all have one thing in common: they speak a distinct language which may offend the beholder. This exhibition seeks to contrast the recent tendency of survey exhibitions circling around painting itself. Questions about what the medium is or still can be are dominant, instead of analyzing its actual contents. Lately, the theoretical discourse and exhibitions have created the impression as if there are deep insecurities in coping with the medium. The representation of contemporary painting seems to be stuck in a crisis – at least in context of institutional exhibitions. There lies a special potential for subversion in painting as the most accessible art genre. As opposed to an installation, for example, a painting is not assumed to be complicated, per se. A picture is easily ascertainable for the human eye, as it does not require much movement in space and corresponds with our optical perception. Therefore the information supplied can be processed promptly. Based on this familiarity, we develop faith. We trust in not being attacked, startled or offended by painting. And precisely that confidence provides ideal circumstances for the exhibited artist to create tension. The prematurely and inconsiderately developed faith of the spectator is consequently broken, undermined and frustrated. Thus, the artworks in the exhibition earn the adjective “evil” by ambushing us with their content. But evil has no quality in itself. It appears as a categorical attribution when we have absolutely no chance to sympathize with our vis-à-vis. However, the question is whether this objection is necessarily justified by a categorical moral instance. Aren’t we obliged to question our thinking, our acting and our ideas when confronted with the maximum divergence from everything we consider as “good”? In this moment of hesitation, the painting reveals its power. The artworks shown in the exhibition Malerei, böse (Painting, evil) compel us to questions our morals and beliefs. It becomes clear that all prevalent normative attributions and inscriptions reflect only our cultural convictions, which are highly debatable. The exhibition is supported by the Ministry of Culture of the Free and Hanseatic City of Hamburg and Sylt Quelle