A photographic image – between an archive and a semblance. Photographs in Tadeusz Różewicz’s The Professor’s Little Knife

This article explores the issue of postmemory and secondary witnessing as dealt with in Tadeusz Różewicz’s 2002 poem The Professor’s Little Knife. The paper presents two photographs which refer to the problem of the Holocaust’s representation and its limits. The first picture comes from the collection of the U.S. Holocaust Memorial Museum; however, the author concealed its origins and changed its appearance so that it resembled a retro nude photograph. The second one is a raw, non-stylized picture of a knife that belonged to Professor Porębski during imprisonment in Auschwitz-Birkenau concentration camp. By using various interpretation methods, such as the deconstruction of an image or empathic reading, the author of this article examines the limits and consequences of treating a photograph as “spectral evidence”.2119520812Przestrzenie Teori

Tadeusza Różewicza architektonika doświadczenia

TADEUSZ RÓŻEWICZ’S ARCHITECTURE OF EXPERIENCEThe article is devoted to Różewicz’s poetic imagination, and above all to the images associated with the motif of the monument. I also regard the motif of the cathedral and the stone as variants of this central topos. The above motifs serve as interpretative trails in the analysis of the essay What Has Remained of the Unwritten Book About Norwid (as well as of the poem An Evening in Norwid’s Honor) which constitutes its fundamental element. I am especially interested in the commemorative dimension of the „monumental” topics and its connection with Różewicz’s concept of autobiographical poetry

Wizualna przestrzeń postpamięci. Poetyka sekundarnego świadectwa w nożyku profesora Tadeusza Różewicza

The visual space of postmemory. The poetics of secondary testimony in Tadeusz Różewicz’s nożyk profesora (professor’s little knife) This essay discusses the problem of postmemory and secondary testimony, including their visual and textual manifestations in Tadeusz Różewicz’s late poem nożyk profesora (2001). The essay deals with theoretical background of the concept of postmemory (according to Marianne Hirsch and Dori Laub) in its psychoanalytical and aesthetical aspects. It focuses on the experimental style and composition of Różewicz’s poem which combines visual (3 photographs) and textual (or, more precise, intertextual) means of expression to articulate a multilayered and polyphonic secondary Holocaust testimony

Endoplasmic reticulum stress in malignancy.

The combination of relative nutrient deprivation and dysregulation of protein synthesis make malignant cells especially prone to protein misfolding. Endoplasmic reticulum stress, which results from protein misfolding within the secretory pathway, has a profound effect on cancer cell proliferation and survival. In this review, we examine the evidence implicating endoplasmic reticulum dysfunction in the pathology of cancer and discuss how recent findings may help to identify novel therapeutic targets

Occurrence and extraction of implantable cardioverter-defibrillator leads with conductor externalization

   Background: The increasing number of patients with implantable cardioverter-defibrillators (ICD) contributes to the rising number of patients qualifying for a transvenous lead extraction (TLE) due to infection, vascular or lead failure related indications. The purpose of this study was to perform a retrospective analysis of the occurrence of conductor externalization in TLE patients and to assess the success rate in the extraction of these leads. Methods: TLE procedure was performed between 2012 and 2014 of 428 electrodes in 259 patients. Out of these, 143 (33.4%) leads in 138 (52.9%) patients were ICD leads. The indications for the TLE in ICD patients were: infection in 37 patients, lead failure in 84 patients, and others in 17 patients. Conductor externalization was observed in 8 ICD leads (5.6%) in 8 (5.8%) patients. The mean dwell­ing time for externalized leads was 87.9 (55 to 132) months compared to 60.1 (3 to 246) months of the remaining 135 ICD leads (p = 0.0329). All externalized leads were successfully and completely extracted using device traction, mechanical telescopic sheaths and/or autorotational cutting sheaths. No complica­tions of lead extraction procedures were observed in 8 patients with externalization. Results: Patients with lead externalization were often in a better New York Heart Association func­tional class (I or II) compared to those in the rest of the study group (p = 0.0212). Conclusions: Conductor externalization is a rare finding in patients undergoing TLE. This occurs with different manufacturers and lead types. In this complication transvenous lead extraction with the mechanical extraction tools can be safely performed.

G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases.

Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly, PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selectivity. However, selectivity was restored by crude cell lysate or purified G-actin, which joined PPP1R15-PP1 to form a stable ternary complex. In crystal structures of the non-selective PPP1R15B-PP1G complex, the functional core of PPP1R15 made multiple surface contacts with PP1G, but at a distance from the active site, whereas in the substrate-selective ternary complex, actin contributes to one face of a platform encompassing the active site. Computational docking of the N-terminal lobe of eIF2a at this platform placed phosphorylated serine 51 near the active site. Mutagenesis of predicted surface-contacting residues enfeebled dephosphorylation, suggesting that avidity for the substrate plays an important role in imparting specificity on the PPP1R15B-PP1G-actin ternary complex.Wellcome Trust, MRC, EU FP7This is the final version of the article. It first appeared from eLife via http://dx.doi.org/10.7554/eLife.04871.00

Actin dynamics tune the integrated stress response by regulating eukaryotic initiation factor 2α dephosphorylation.

Four stress-sensing kinases phosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α) to activate the integrated stress response (ISR). In animals, the ISR is antagonised by selective eIF2α phosphatases comprising a catalytic protein phosphatase 1 (PP1) subunit in complex with a PPP1R15-type regulatory subunit. An unbiased search for additional conserved components of the PPP1R15-PP1 phosphatase identified monomeric G-actin. Like PP1, G-actin associated with the functional core of PPP1R15 family members and G-actin depletion, by the marine toxin jasplakinolide, destabilised the endogenous PPP1R15A-PP1 complex. The abundance of the ternary PPP1R15-PP1-G-actin complex was responsive to global changes in the polymeric status of actin, as was its eIF2α-directed phosphatase activity, while localised G-actin depletion at sites enriched for PPP1R15 enhanced eIF2α phosphorylation and the downstream ISR. G-actin's role as a stabilizer of the PPP1R15-containing holophosphatase provides a mechanism for integrating signals regulating actin dynamics with stresses that trigger the ISR.This work was funded by the Medical Research Council (UK) (MRC Ref G1002610) and a Wellcome Trust Strategic Award for core facilities to the Cambridge Institute for Medical Research (CIMR, Wellcome 100140). SJM holds a Senior Clinical Research Fellowship from the Medical Research Council (MRC Ref G1002610). DR is a Wellcome Trust Principal Research Fellow (Wellcome 084812/Z/08/Z). The June Hancock Mesothelioma Research Fund funded LED (JH09-2); the British Lung Foundation funded HJC (APHD11-4); CD is a member of the CIMR PhD programme funded by the Wellcome Trust; and VP holds a Diabetes UK Arthur and Sadie Pethybridge PhD Studentship.This is the final published version. It first appeared at http://elifesciences.org/content/4/e04872

Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.

Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA). Efficient functioning of the endoplasmic reticulum (ER) is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR). Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR) which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host