Zastosowanie lewosimendanu u chorych z ostrą niewydolnością serca z objawami małego rzutu minutowego serca: opis serii przypadków

The report presents single centre experience in application of levosimendan in patients with acute heart failure with low cardiacoutput. All patients underwent haemodynamic measurement before and after administration of the drug. Levosimendanimproved haemodynamics and was useful in this subpopulation of patients

Ostry zespół wieńcowy indukowany stresem — trudności diagnostyczne w rozpoznaniu zespołu tako-tsubo

Kardiomiopatia tako-tsubo jest formą przemijających zaburzeń kurczliwości lewej komorycechującą się akinezą koniuszka z hiperkinezą segmentów podstawnych. Charakterystycznącechą tako-tsubo jest związek czasowy z silnym stresem emocjonalnym lub fizycznym. Kardiomiopatiastresowa występuje u około 1–2% chorych ze wstępnym rozpoznaniem zawału serca,ze zdecydowaną przewagą u kobiet w wieku 60–80 lat. W pracy przedstawiono 3 przypadkipacjentek hospitalizowanych z podejrzeniem ostrego zespołu wieńcowego, u których na podstawiedalszych badań (koronarografii, badania echokardiograficznego i badań laboratoryjnych)ostatecznie rozpoznano kardiomiopatię tako-tsubo

Iron status and myocardial injury while recovering from acute myocarditis

Introduction. The pathophysiology of acute myocarditis (MCD) and subsequent recovery involves complex interplay between the virulence of pathogen, host immunity with possible genetic-based immune dysregulation, comorbidities and environmental factors. Precise identification of patients with increased risk of subsequent post-inflammatory cardiomyopathy is challenging. Abnormal iron status not only is a hallmark of immune activation but also plays a role in the development of cardiomyopathy, hence we investigated whether iron indices relate to myocardial injury in patients with acute MCD. Material and methods. Consecutive patients hospitalized for acute MCD in two cardiology centers were prospectively enrolled. We analyzed clinical characteristics, cardiac magnetic resonance (CMR) findings and biomarkers of myocardial necrosis, neurohormonal activation, inflammation, and comprehensive systemic iron status from index hospitalization and an ambulatory control visit after 6 months. Healthy volunteers were control group. Results. We enrolled 40 patients hospitalized for acute myocarditis (age: 32 ± 9 years, male gender: 98%). In-hospital serum ferritin correlated with CMR late gadolinium enhancement (LGE) mass (r = 0.537, p &lt; 0.001) and global T2 ratio (r = 0.360, p = 0.03). LGE, regional abnormalities in myocardial T1 relaxation time and elevated extracellular volume persisted after 6 months of recovery in comparison to healthy controls. Persistent LGE mass correlated with lower transferrin saturation and serum iron at the ambulatory visit (r = –0.520, p = 0.03; and r = –0.465, p = 0.04; respectively). Conclusions. Acute-phase reactant ferritin relates to myocardial injury in the acute phase of MCD, whereas in the recovery phase residual fibrosis is greater in subjects with more profound functional iron deficiency, the latter reflecting, to some extent, systemic low-grade inflammation.Introduction. The pathophysiology of acute myocarditis (MCD) and subsequent recovery involves complex interplay between the virulence of pathogen, host immunity with possible genetic-based immune dysregulation, comorbidities and environmental factors. Precise identification of patients with increased risk of subsequent post-inflammatory cardiomyopathy is challenging. Abnormal iron status not only is a hallmark of immune activation but also plays a role in the development of cardiomyopathy, hence we investigated whether iron indices relate to myocardial injury in patients with acute MCD. Material and methods. Consecutive patients hospitalized for acute MCD in two cardiology centers were prospectively enrolled. We analyzed clinical characteristics, cardiac magnetic resonance (CMR) findings and biomarkers of myocardial necrosis, neurohormonal activation, inflammation, and comprehensive systemic iron status from index hospitalization and an ambulatory control visit after 6 months. Healthy volunteers were control group. Results. We enrolled 40 patients hospitalized for acute myocarditis (age: 32 ± 9 years, male gender: 98%). In-hospital serum ferritin correlated with CMR late gadolinium enhancement (LGE) mass (r = 0.537, p < 0.001) and global T2 ratio (r = 0.360, p = 0.03). LGE, regional abnormalities in myocardial T1 relaxation time and elevated extracellular volume persisted after 6 months of recovery in comparison to healthy controls. Persistent LGE mass correlated with lower transferrin saturation and serum iron at the ambulatory visit (r = –0.520, p = 0.03; and r = –0.465, p = 0.04; respectively). Conclusions. Acute-phase reactant ferritin relates to myocardial injury in the acute phase of MCD, whereas in the recovery phase residual fibrosis is greater in subjects with more profound functional iron deficiency, the latter reflecting, to some extent, systemic low-grade inflammation

Comparative proteomics identifies Schlafen 5 (SLFN5) as a herpes simplex virus restriction factor that suppresses viral transcription

Intrinsic antiviral host factors confer cellular defence by limiting virus replication and are often counteracted by viral countermeasures. We reasoned that host factors that inhibit viral gene expression could be identified by determining proteins bound to viral DNA (vDNA) in the absence of key viral antagonists. Herpes simplex virus 1 (HSV-1) expresses E3 ubiquitin-protein ligase ICP0 (ICP0), which functions as an E3 ubiquitin ligase required to promote infection. Cellular substrates of ICP0 have been discovered as host barriers to infection but the mechanisms for inhibition of viral gene expression are not fully understood. To identify restriction factors antagonized by ICP0, we compared proteomes associated with vDNA during HSV-1 infection with wild-type virus and a mutant lacking functional ICP0 (ΔICP0). We identified the cellular protein Schlafen family member 5 (SLFN5) as an ICP0 target that binds vDNA during HSV-1 ΔICP0 infection. We demonstrated that ICP0 mediates ubiquitination of SLFN5, which leads to its proteasomal degradation. In the absence of ICP0, SLFN5 binds vDNA to repress HSV-1 transcription by limiting accessibility of RNA polymerase II to viral promoters. These results highlight how comparative proteomics of proteins associated with viral genomes can identify host restriction factors and reveal that viral countermeasures can overcome SLFN antiviral activity

Zarządzanie przepływem i ochroną informacji

Publikacja recenzowana / Peer-reviewed publicationPrzedstawione wydawnictwo stanowi zasadniczy plon obrad konferencji naukowej zorganizowanej przez Katedrę Zarządzania Informacją na Wydziale Ekonomii i Zarządzania w dniach 25—26 marca 2007 roku. Ambicją organizatorów konferencji było włączenie w tok dyskusji licznych przedstawicieli praktyki gospodarczej, mediów oraz studentów. W odpowiedzi na zaproszenie do udziału w konferencji napłynęło ponad dwadzieścia referatów problemowych, z których kilka, ze względu na problematykę ściśle wiążącą się z zagadnieniami bezpieczeństwa, zostanie opublikowanych w nowym czasopiśmie naukowym Krakowskiej Szkoły Wyższej im. Andrzeja Frycza Modrzewskiego pt. „Problemy Bezpieczeństwa”. Autorami wszystkich przygotowanych tekstów są uznani eksperci w dziedzinie przepływu i ochrony informacji, a także młodzi pracownicy szkół wyższych i przedstawiciele praktyki gospodarczej. Patronat medialny objęły pisma o ogólnopolskim zasięgu i uznanej renomie: „Przegląd Organizacji”, „CSO Magazyn Zarządzających Bezpieczeństwem” i „Czasopismo Zabezpieczenia”. Całość rozważań Autorów podzielona została na trzy części, ściśle ze sobą powiązane. Część pierwsza grupuje teksty pod wspólnym tytułem „Przepływ, przetwarzanie i ochrona informacji we współczesnych systemach zarządzania”, część druga nosi tytuł: „Informacja jako determinanta tworzenia wartości dodanej oraz przewagi konkurencyjnej”, część trzecia zaś omawia „Zarządzanie wiedzą w wybranych dziedzinach aktywności gospodarczej i publicznej”

Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition

Abstract Background Epithelial to mesenchymal transition (EMT) plays a crucial role in cancer propagation. It can be orchestrated by the activation of multiple signaling pathways, which have been found to be highly coordinated with many epigenetic regulators. Although the mechanism of EMT has been studied over decades, cross talk between signaling and epigenetic regulation is not fully understood. Results Here, we present a time-resolved multi-omics strategy, which featured the identification of the correlation between protein changes (proteome), signaling pathways (phosphoproteome) and chromatin modulation (histone modifications) dynamics during TGF-β-induced EMT. Our data revealed that Erk signaling was activated in 5-min stimulation and structural proteins involved in cytoskeleton rearrangement were regulated after 1-day treatment, constituting a detailed map of systematic changes. The comprehensive profiling of histone post-translational modifications identified H3K27me3 as the most significantly up-regulated mark. We thus speculated and confirmed that a combined inhibition of Erk signaling and Ezh2 (H3K27me3 methyltransferase) was more effective in blocking EMT progress than individual inhibitions. Conclusions In summary, our data provided a more detailed map of cross talk between signaling pathway and chromatin regulation comparing to previous EMT studies. Our findings point to a promising therapeutic strategy for EMT-related diseases by combining Erk inhibitor (singling pathway) and Ezh2 inhibitor (epigenetic regulation)

Low Resolution Data-Independent Acquisition in an LTQ-Orbitrap Allows for Simplified and Fully Untargeted Analysis of Histone Modifications

Label-free peptide quantification in liquid chromatography–mass spectrometry (LC–MS) proteomics analyses is complicated by the presence of isobaric coeluting peptides, as they generate the same extracted ion chromatogram corresponding to the sum of their intensities. Histone proteins are especially prone to this, as they are heavily modified by post-translational modifications (PTMs). Their proteolytic digestion leads to a large number of peptides sharing the same mass, while carrying PTMs on different amino acid residues. We present an application of MS data-independent acquisition (DIA) to confidently determine and quantify modified histone peptides. By introducing the use of low-resolution MS/MS DIA, we demonstrate that the signals of 111 histone peptides could easily be extracted from LC–MS runs due to the relatively low sample complexity. By exploiting an LTQ-Orbitrap mass spectrometer, we parallelized MS and MS/MS scan events using the Orbitrap and the linear ion trap, respectively, decreasing the total scan time. This, in combination with large windows for MS/MS fragmentation (50 <i>m</i>/<i>z</i>) and multiple full scan events within a DIA duty cycle, led to a MS scan cycle speed of ∼45 full MS per minute, improving the definition of extracted LC–MS chromatogram profiles. By using such acquisition method, we achieved highly comparable results to our optimized acquisition method for histone peptide analysis (<i>R</i>² correlation > 0.98), which combines data-dependent acquisition (DDA) and targeted MS/MS scans, the latter targeting isobaric peptides. By using DIA, we could also remine our data set and quantify 16 additional isobaric peptides commonly not targeted during DDA experiments. Finally, we demonstrated that by performing the full MS scan in the linear ion trap, we achieve highly comparable results as when adopting high-resolution MS scans (<i>R</i>² correlation 0.97). Taken together, results confirmed that histone peptide analysis can be performed using DIA and low-resolution MS with high accuracy and precision of peptide quantification. Moreover, DIA intrinsically enables data remining to later identify and quantify isobaric peptides unknown at the time of the LC–MS experiment. These methods will open up epigenetics analyses to the proteomics community who do not have routine access to the newer generation high-resolution MS/MS generating instruments

Exploration of the Nuclear Proteomes in the Ciliate <i>Oxytricha trifallax</i>

Nuclear dimorphism is a fundamental feature of ciliated protozoa, which have separate somatic and germline genomes in two distinct organelles within a single cell. The transcriptionally active somatic genome, contained within the physically larger macronucleus, is both structurally and functionally different from the silent germline genome housed in the smaller micronucleus. This difference in genome architecture is particularly exaggerated in Oxytricha trifallax, in which the somatic genome comprises tens of thousands of gene-sized nanochromosomes maintained at a high and variable ploidy, while the germline has a diploid set of megabase-scale chromosomes. To examine the compositional differences between the nuclear structures housing the genomes, we performed a proteomic survey of both types of nuclei and of macronuclear histones using quantitative mass spectrometry. We note distinct differences between the somatic and germline nuclei, with many functional proteins being highly enriched in one of the two nuclei. To validate our conclusions and the efficacy of nuclear separation, we used protein localization through a combination of transformations and immunofluorescence. We also note that the macronuclear histones strikingly display only activating marks, consistent with the conclusion that the macronucleus is the hub of transcription. These observations suggest that the compartmentalization of different genome features into separate structures has been accompanied by a similar specialization of nuclear components that maintain and facilitate the functions of the genomes specific to each nucleus

Wnt5a signaling induced phosphorylation increases APT1 activity and promotes melanoma metastatic behavior

Wnt5a has been implicated in melanoma progression and metastasis, although the exact downstream signaling events that contribute to melanoma metastasis are poorly understood. Wnt5a signaling results in acyl protein thioesterase 1 (APT1) mediated depalmitoylation of prometastatic cell adhesion molecules CD44 and MCAM, resulting in increased melanoma invasion. The mechanistic details that underlie Wnt5a-mediated regulation of APT1 activity and cellular function remain unknown. Here, we show Wnt5a signaling regulates APT1 activity through induction of APT1 phosphorylation and we further investigate the functional role of APT1 phosphorylation on its depalmitoylating activity. We found phosphorylation increased APT1 depalmitoylating activity and reduced APT1 dimerization. We further determined APT1 phosphorylation increases melanoma invasion in vitro, and also correlated with increased tumor grade and metastasis. Our results further establish APT1 as an important regulator of melanoma invasion and metastatic behavior. Inhibition of APT1 may represent a novel way to treat Wnt5a driven cancers