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Objective: Use of tumour necrosis factor inhibitors (TNFi) has proved to be an important step forward in the treatment of axial spondyloarthritis (axSpA), but the duration of the therapy as well as the management in case of low disease activity (LDA) or remission are not clearly established. Currently, the identification of potential predictors associated with the treatment discontinuation is the basic purpose of many clinical studies. The aim of this study was to analyze the influence of the discontinuation of TNFi therapy on the disease activity in patients with low disease activity. Material and methods: The study included 65 patients; 47 of patients (72%) were treated with etanercept, 16 (2%) with adalimumab and 2 (3%) with infliximab. Results: The mean age of the patients was 45 years, the mean BASDAI score was 6.8 and VAS for low back pain was 76 mm at baseline. 54 patients with axSpA (83%) achieved LDA after 9 months of anti-TNF therapy. During follow-up 40 patients (74% of patients with LDA) had an increase of the disease activity after mean 14 weeks and needed to restart the treatment with TNFi. After restart of the therapy LDA was regained in all patients after mean 7 weeks. 11 patients (17%) have never achieved LDA and 14 patients (22%) had LDA longer than 6 months without relapse. At baseline higher levels of CRP and ESR were observed in patients with relapse of the disease at the end of treatment and with LDA shorter than 6 months. Conclusions: Changes in the values of disease activity indicators (CRP, ESR) correlated with more stable response to TNFi therapy. Over 50% of patients who were treated with TNFi needed to restart the therapy. Treatment resumption allowed to regain a good clinical effect among affected patients.

On February 15, 2017, the United States Patent and Trademark Office's Patent Trial and Appeal Board announced its long-awaited decision finding no interference-in-fact between patents and patent applications directed to CRISPR-Cas9 owned by Broad Institute, Inc. et al. and patent applications owned by Regents of the University of California et al. The decision found that the CRISPR-Cas9 gene-editing system in a eukaryotic environment (as generally claimed by Broad Institute) was found to be patentably distinct from a CRISPR-Cas9 gene-editing system in any environment, including in prokaryotic cells or in vitro (as claimed by the University of California), “because one of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in a eukaryotic environment.” Therefore, no interference of the claims was found and the proceedings were terminated. This decision has been appealed to the Federal Circuit Court of Appeals. The background, implications of this deci...

The methylation of histone lysine residues modifies chromatin conformation and regulates the expression of genes implicated in cell metabolism. Lysine-specific demethylase 1 (LSD1) is a flavin-dependent monoamine oxidase that can demethylate mono- and dimethylated histone lysines 4 and 9 (H3K4 and H3K9). The removal of methyl groups from the lysine residues of histone and non-histone proteins was found to be an important regulatory factor of cell proliferation. However, its role has not been fully elucidated. In this study, we assessed LSD1-mediated cell cycle progression using a human endothelial cell model. The short hairpin RNA knockdown of LSD1 inhibits the G2/M phase of cell cycle progression by checkpoint kinase 1 (Chk1) phosphorylation (S137). We observed elevated DNA damage, which was consistent with the increased detection of double-strand breaks as well as purines and pyrimidines oxidation, which accompanied the activation of ATR/ATRIP signaling by H2AXS139 phosphorylation. The irreversible pharmacological inhibition of LSD1 by 2-phenylcyclopropylamine (2-PCPA) inactivated its enzymatic activity, causing significant changes in heterochromatin and euchromatin conformation assessed by chromatin assembly factor 1 subunit A (CAF1A) and heterochromatin protein 1 isoform &alpha, and &gamma, (HP1&alpha, /&gamma, ) immunofluorescence analysis. We conclude that the knockdown of LSD1 in endothelial cells leads to increased HP1-positive chromatin, the stimulation of DNA repair processes, and the dysregulation of proliferation machinery.

ObjectivesParkinson’s disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function.MethodsDemographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration.ResultsCompared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314).ConclusionThe three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.

Butyrate and R-β-hydroxybutyrate are two related short chain fatty acids naturally found in mammals. Butyrate, produced by enteric butyric bacteria, is present at millimolar concentrations in the gastrointestinal tract and at lower levels in blood; R-β-hydroxybutyrate, the main ketone body, produced by the liver during fasting can reach millimolar concentrations in the circulation. Both molecules have been shown to be histone deacetylase (HDAC) inhibitors, and their administration has been associated to an improved metabolic profile and better cellular oxidative status, with butyrate inducing PGC1α and fatty acid oxidation and R-β-hydroxybutyrate upregulating oxidative stress resistance factors FOXO3A and MT2 in mouse kidney. Because of the chemical and functional similarity between the two molecules, we compared here their impact on multiple cell types, evaluating i) histone acetylation and hydroxybutyrylation levels by immunoblotting, ii) transcriptional regulation of metabolic and inflammatory genes by quantitative PCR and iii) cytokine secretion profiles using proteome profiling array analysis. We confirm that butyrate is a strong HDAC inhibitor, a characteristic we could not identify in R-β-hydroxybutyrate in vivo nor in vitro. Butyrate had an extensive impact on gene transcription in rat myotubes, upregulating PGC1α, CPT1b, mitochondrial sirtuins (SIRT3-5), and the mitochondrial anti-oxidative genes SOD2 and catalase. In endothelial cells, butyrate suppressed gene expression and LPS-induced secretion of several pro-inflammatory genes, while R-β-hydroxybutyrate acted as a slightly pro-inflammatory molecule. Our observations indicate that butyrate induces transcriptional changes to a higher extent than R-β-hydroxybutyrate in rat myotubes and endothelial cells, in keep with its HDAC inhibitory activity. Also, in contrast with previous reports, R-β-hydroxybutyrate, while inducing histone β-hydroxybutyrylation, did not display a readily detectable HDAC inhibitor activity and exerted a slight pro-inflammatory action on endothelial cells.

This doctoral thesis concerns the everyday life of soldiers on the African front in the years 1941-1943, The theoretical part concentrates on presenting the two branches of sociology: sociology of war and sociology of everyday life, indicating their underlying assumptions and their place in the mainstream of sociology. The categories presented in this section, e.g., space, interpersonal relationships, laughter, fear, and fixation, have been, within the research process, applied to the everyday life of soldiers. The methodological part contains a description of the biographical method, content analysis, and case study, with a detailed account for nomenclature later in the research part. The importance of qualitative research is also emphasized, as, without it, this work could not arise. Part of the test consists of four case studies on the following team formations: Deutsches Afrika Korps, Luftwaffe in Africa, British 8. Army and the Desert Air Force. As can be seen, the research included both the land and air armies. All four case studies have been categorized according to the same categories - e.g., hygiene, food, everyday life on the battlefield, free time in the desert, et cetera - in order to enable a comparison of presented categories between specific military units. Besides, using a detailed list of contents, the reader may remind themselves of the importance of the concept of the theoretical part at any time.

There is a great need for non-invasive tools that enable improved insight into the underlying causes of battery ageing. In this project we investigate cycling and calendar ageing effects on high energy commercial cylindrical cells (NCA|Si-Gr), by tracking thermodynamic and kinetic aspects by the employment of entropy profiling, differential voltage and incremental capacity analysis (DVA/ICA), and differential thermal voltammetry (DTV). Two groups of three cells from the same batch are being subjected to different ageing scenarios, both at 45°C: group A is under calendar aging at 75 % state of charge - SoC at which we observed the most accelerated calendric aging for these cells - and group B, which is being cycled continuously at the maximum current allowed by the manufacturer. To ensure minimal temperature fluctuations during tests and allow proper comparative DTV, cells were submerged in a high conductivity dielectric fluid bath. We revised Osswald’s approach for entropy profiling [1], and also increased the number of titration steps in entropy profiling to 63, for both charge and discharge. Fig. 1 shows the results for the initial 40-day aging period, comparing ICA and entropy profiles, before and after ageing. In addition to the capacity fade of 2.2 % and 6.2 % for groups A and B respectively (Figure 1a), the loss of sharpness present in the ICA peaks is also present in the entropy curves (features A1-A4 in Fig. 1b). This can be attributed to a more heterogeneous lithium distribution and a change in lithium inventory. To track the reversibility of ageing and the time scales of passive electrode effects [2], both groups of cells will be submitted to rest periods after which entropy, DTV and ICA experiments will be periodically repeated. References [1] P.J. Osswald, M. Del Rosario, J. Garche, A. Jossen, H.E. Hoster, Electrochim. Acta 177 (2015) 270–276. [2]M. Lewerenz, G. Fuchs, L. Becker, D.U. Sauer, J. Energy Storage 18 (2018) 149–159. Figure 1

Rather than being a passive barrier between circulating blood and smooth muscle cells and the underlying tissues, the endothelium is a fundamental functional component of the vasculature, and could be viewed as the largest human endocrine gland/organ, secreting multiple pro-/antiangiogenic factors, cytokines and low-molecular-weight mediators controlling the vascular tone. The location of endothelium, at the interface between the circulation and the tissues, makes this epithelial layer particularly exposed to physical and chemical cues coming from the bloodstream. In response to such stimuli, the endothelium modulates its morphology and functions to maintain vascular homeostasis. Dietary components significantly affect the proper functioning of the endothelium. High-calories and high-fat western diets, in the long term, cause endothelial dysfunction, which is a major contributor to the development of the metabolic syndrome and its pathological consequences, including atherosclerosis, diabetes, and hypertension. On the contrary, plant-derived antioxidant molecules and polyphenols have been shown to exert beneficial effects on endothelial function. Extensive research in the last decade has clearly shown the close relationship between food intake, dietary habits, and gene expression, which is driven by the action of macro- and micronutrients on chromatin regulation. Nutrient-induced chromatin epigenetic modifications via DNA methylation and histone post-translational modifications, especially in the context of the western diet, significantly contribute to the dysregulation of endothelial functioning. Here, we review the current understanding on how dietary components (macronutrients, antioxidants), acting on epigenetic mechanisms, regulate endothelial physiology, and physiopathology. © 2016 BioFactors, 2016

Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

Background The etiology of axial spondyloarthritis (axSpA) is not fully elucidated. Research continues in determining the mechanisms responsible for initiation of the disease process, its maintenance and development. Objectives The aim of this study was to evaluate the expression of transcription factors STAT (signal transducer and activator of transcription) and NF-κB (nuclear factor kappa B) as well as Janus kinase3 (JAK3) in the peripheral blood leukocytes. We also analyzed the connection between the degree of activation of transcription factors and the disease activity. Material/methods The study involved 46 patients with axSpA and 19 healthy individuals who comprised the control group. The expression of NF-κB, STAT1, STAT3, STAT4, STAT5, STAT6, and JAK3 in peripheral blood leukocytes was assessed. To determine the degree of activation of transcription factors STAT-s and NF-κB and JAK3 kinase, the immunocytochemistry method was used. For location of the factors, the primary monoclonal anti-NF-κB, anti-JAK3 and polyclonal anti-STAT-s antibodies were used (Chemicon International, USA, Abcam, Cambridge, UK), and the set of antibodies Novocastain Super ABC Kit (Novocastra, UK). Results Expression of STAT1, STAT3, STAT4, STAT5, STAT6, NF-κB and JAK3 was statistically higher in the group of patients with axSpA than in the control group. There was a positive correlation with ESR values and expression of STAT4. There was no correlation between STAT, NF-κB, and JAK3 expression and ASDAS, BASDAI, and BASFI. Nine patients were treated with TNF-α inhibitors. The expression of NF-κB and STAT6 was higher in the group treated with TNF-α inhibitors, even though disease activity in these patients was shown to be lower than in those not receiving such treatment (ASDAS = 1.34±0.51 vs. 3.52±0.90, BASDAI = 2.34±1.92 vs. 5.51±2.41). Conclusions In the group of patients with axSpA compared with the control group, higher expression of the transcription factors STAT and NF-κB as well as JAK3 was observed. Due to its crucial roles in inflammation and autoimmunity, STAT4 may have promise as an effective therapeutic target for axSpA.

Epigenetic mechanisms, including histone post-translational modifications, are central regulators of cell cycle control. The euchromatic G9a histone methyltransferase (G9a HMT) is a key enzyme catalyzing histone H3 methylation on lysines 9 and 27, and its dysregulation has been linked to uncontrolled proliferation of tumor cells. Here, we have investigated the effect of G9a HMT silencing on cell proliferation of microvascular endothelial cells, a process necessary to sustain tumor growth through the formation of the vascular capillary network. Inhibition of G9a HMT activity in human microvascular endothelial cells (HMEC-1) was performed either pharmacologically, by treatment of cells with BIX-01294 or chaetocin, or transcriptionally, using shRNA. Cell viability and proliferation were examined using the resazurin reduction assay, flow cytometry and immunostaining of phosphorylated checkpoint kinase 1 (pSer317Chk1). Expression of cell cycle- and redox homeostasis-related genes was determined by quantitative PCR. Reactive oxygen species production was measured by oxidation of the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate and the cell's total antioxidant capacity by using the ABTS assay. Inhibition of G9a HMT activity by BIX-01294 treatment or by shRNA attenuated the proliferation of HMEC-1, nuclear localization of phosphorylated Chk1, and induced cell cycle arrest in G1 phase. Transcriptional analysis demonstrated increased gene expression of the cyclin-dependent kinase (CDK) inhibitor p21, and also of Rb1, in BIX-01294 treated cells. Decreased proliferation rate was accompanied by enhanced antioxidant potential of HMEC-1 cells, as demonstrated by reduced production of reactive oxygen species, increased total antioxidant capacity and expression of the antioxidant enzymes catalase and superoxide dismutase 1. Collectively, our results demonstrate of the central role of G9a HMT in the promotion of endothelial cells proliferation, and suggest that endothelial G9a HMT may be a target in the treatment of vascular proliferative disorders and tumor neovascularization.

The adaptor protein p66Shc modulates cellular redox status integrating oxidative stress with mitochondrial stress responses. Upon oxidative stress, p66Shc is translocated to mitochondria or mitochondria-associated membranes in a multi-step process, resulting in locally increased reactive oxygen species production. This signaling pathway is believed to be important in the context of drug-induced organ toxicity. The use of anthracyclines as anticancer agents is limited due to a dose-dependent and cumulative toxicity resulting in cardiomyopathy. Treatment with the anthracycline doxorubicin (DOX) results in a dose-dependent and cumulative cardiotoxicity which is mediated, at least in part, by increased oxidative stress. In the present study, we investigated for the first time whether p66Shc signaling is activated during DOX treatment of the rat cardiomyoblast H9c2 cell line. We further tested whether the transcriptional factor FoxO3a, which activates target genes responsible for apoptosis and cell cycle arrest, is also involved in p66Shc-dependent redox signaling pathway. Our results suggest that DOX treatment induces p66Shc protein up-regulation specifically in nuclear fractions. Increased nuclear expression of FoxO3a was also detected in H9c2 cells after DOX treatment. Treatment with the antioxidant and protein kinase C (PKC-β) inhibitor hispidin decreased DOX-induced activation of caspase 9 and p66Shc alterations. Taking together, we hypothesize that p66Shc signaling is involved in the activation of stress/toxicity responses elicited by the treatment of H9c2 cells with DOX. Hence, the selective inhibition of this redox pathway may be a promising therapeutic approach to circumvent DOX cardiotoxicity.

Background MTX is still a basic medicament used in treatment of patients with RA. One of its adverse reaction is its hepatoxicity. Previous studies have established high diagnostic accuracy of the ELF score to assess hepatic fibrosis in chronic viral hepatitis and fatty liver disease. Objectives The aim of the research was the evaluation of the usefulness of ELF markings, by patients treated with MTX, as an indicator which shows potential liver damage. Methods In the research were analyzed results of 96 patients with RA treated with MTX. Average age of patients was 60 (19–85 years old), median of body mass was 70 kg (46–140), median of BMI was 26 (16–46). Average time of taking MTX were 4 years and median of the accumulated dose was 3140 mg (12,5–27400mg). Disease activity in the moment of evaluation, evaluated by DAS 28, was 4,3 (0,98–8,42). Achieved results ELF, PIIINP were correlated with body mass, BMI, dose of MTX, other illnesses (e.g. diabetes), taken nonsteroidal anti-inflammatory drugs and statins. In statistical analysis were used Pearson correlation and U Mann-Whitney test. Results The ELF values correlated with age, accumulated dose and DAS 28. Along with the increase of accumulated dose of MTX, disease activity and by older patients, were observed higher ELF values (the differences were statistically significant). The PIIINP values correlated with patients9 body mass, accumulated dose of MTX and disease activity, evaluated by DAS 28. The differences were statistically significant. Along with the increase of body mass, accumulated dose and DAS 28, were observed higher values of PIIINP. Patients with diabetes had statistically higher values of PIINP (average: 11.13, median: 11,38), than patients without diabetes (average: 8.06, median: 7.15). There was observed no relationship between ELF and PIIINP results with taken nonsteroidal anti-inflammatory drugs and statins. Conclusions The ELF test, and one of its elements, PIIINP, may be useful in the evaluation of patients with higher probability of hepatotoxic effect of MTX. Special attention should be paid to older, obese patients, with diabetes, patients who take higher accumulated dose of MTX and with higher disease activity. Disclosure of Interest None declared

Conventional cooling approaches that target either a singular tab or outer surface of common format cylindrical lithium-ion battery cells suffer from a high cell thermal resistance. Under an aggressive duty cycle, this resistance can result in the formation of large in-cell temperature gradients and high hot spot temperatures, which are known to accelerate ageing and further reduce performance. In this paper, a novel approach to internal thermal management of cylindrical battery cells to lower the thermal resistance for heat transport through the inside of the cell is investigated. The effectiveness of the proposed method is analysed for two common cylindrical formats when subject to highly aggressive electrical loading conditions representative of a high performance electric vehicle (EV) and hybrid electric vehicle (HEV). A mathematical model that captures the dominant thermal properties of the cylindrical cell is created and validated using experimental data. Results from the extensive simulation study indicate that the internal cooling strategy can reduce the cell thermal resistance by up to 67.8 ± 1.4% relative to single tab cooling, and can emulate the performance of a more complex pack-level double tab cooling approach whilst targeting cooling at a single tab.\ud \ud

Flame retardant composites must perform their protective roles permanently, also under conditions of intermittent or long-term exposure to sunlight, moisture or increased temperature. The aim of our work was characterization of the thermo-oxidative ageing (90 °C) and the changes in flammability of ethylene-vinyl acetate copolymer composites with 40 and 60 wt.% of magnesium hydroxide. The neat polymer and its composites were investigated for their thermal (DSC) and structural (FTIR) characteristics as well as their density, melt flow index, tensile properties and combustibility during ageing test. As FTIR results identified the different carbonyl groups in copolymer were created, the highest oxidation intensity was observed for neat copolymer. That process was accompanied by the scission of the polymer macromolecules, especially for first 700 h of thermal ageing. Thermo-oxidative ageing resulted also in the reduction of flammability of the test materials. The highest reduction was observed for neat polymer. The changes in some properties as analysed both for the copolymer and for its composites after over 700 h of ageing were indicative for initiation of cross-linking of copolymer molecules after that time. Copyright © 2014 John Wiley & Sons, Ltd.

International audience; Posttranslational modifications of histone tails can alter chromatin structure and regulate gene transcription. While recent studies implicate the lysine/arginine protein methyltransferases in the regulation of genes for endothelial metabolism, the role of AMI-1 and AMI-5 compounds in angiogenesis remains unknown. Here, we show that global inhibition of arginine and lysine histone methyltransferases (HMTs) by AMI-5 induced an angiostatic profile in human microvascular endothelial cells and human umbilical vein endothelial cells. Based on FACS analysis, we found that inhibition of HMTs significantly affects proliferation of endothelial cells, by suppressing cell cycle progression in the G0/G1 phase. Immunofluorescent studies of the endothelial cells replication pattern by 5-ethynyl-2'-deoxyuridine incorporation disclosed that AMI-5, and the arginine methyltransferase inhibitor AMI-1, induced heterochromatin formation and a number of nuclear abnormalities, such as formation of micronuclei (MNs) and nucleoplasmic bridges (NPBs), which are markers of chromosomal instability. In addition to the modification of the cell cycle machinery in response to AMIs treatment, also endothelial cells migration and capillary-like tube formation processes were significantly inhibited, implicating a stimulatory role of HMTs in angiogenesis.

Diabetes mellitus is a chronic disease caused by a deficiency in the production of insulin and/or by the effects of insulin resistance. Insulin deficiency leads to hyperglycemia which is the major initiator of diabetic cardiovascular complications escalating with time and driven by many complex biochemical and molecular processes. Four hypotheses, which propose mechanisms of diabetes-associated pathophysiology, are currently considered. Cardiovascular impairment may be caused by an increase in polyol pathway flux, by intracellular advanced glycation end-products formation or increased flux through the hexosamine pathway. The latter of these mechanisms involves activation of the protein kinase C. Cellular and mitochondrial metabolism alterations observed in the course of diabetes are partially associated with an excessive production of reactive oxygen species (ROS). Among many processes and factors involved in ROS production, the 66 kDa isoform of the growth factor adaptor shc (p66Shc protein) is of particular interest. This protein plays a key role in the control of mitochondria-dependent oxidative balance thus it involvement in diabetic complications and other oxidative stress based pathologies is recently intensively studied. In this review we summarize the current understanding of hyperglycemia induced cardiac mitochondrial dysfunction with an emphasis on the oxidative stress and p66Shc protein. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

Background Patients with diabetes are at a high risk of developing both micro- and macrovascular disease. Hyperglycaemia seems to be the main factor in the pathogenesis of diabetic cardiomyopathy, often based on increased oxidative stress. Carvedilol, a β-adrenergic blocker, has intrinsic antioxidant properties and was previously described to be effective in the protection of cardiac mitochondria against oxidative stress. The objective of this study was to evaluate the effect of carvedilol on hyperglycaemia-induced oxidative damage and mitochondrial abnormalities in cardiac and skeletal muscle in streptozotocin-treated rats. Materials and methods Body mass, blood glucose, the level of protein carbonylation, caspase-9- and caspase-3-like activities, mitochondrial proteins, the status of antioxidant defence system and stress-related proteins were evaluated in streptozotocin vs streptozotocin + carvedilol (1 mg/kg/day)-treated rats. Results The results showed that carvedilol decreased blood glucose in streptozotocin-treated animals. Content of catalase in the heart and SOD2, SOD1 and catalase in skeletal muscle were increased by carvedilol treatment in streptozotocin-treated animals. At this particular time point, streptozotocin-induced hyperglycaemia did not cause caspase activation or increase in protein carbonylation status. The data showed that carvedilol increased the level of antioxidant enzymes, what may contribute to preserve cell redox balance during hyperglycaemia. We also showed here for the first time that carvedilol effects on streptozotocin-treated rats are tissue dependent, with a more predominant effect on skeletal muscle. Conclusions Based on data showing modulation of the antioxidant network in the heart, carvedilol may be beneficial in diabetic patients without advanced disease complications, delaying their progression.

Polyethylene grafted with itaconic acid was subjected to weathering under laboratory accelerated conditions. The course of the photo-oxidative degradation process of that material was studied by FTIR spectroscopy both through quantitative measurements of changes in absorbance values at selected wave numbers and through measurements of surface area values for absorption bands which were separated by means of deconvolution. The use of both those procedures of quantitative determinations resulted in a general conclusion that the oxidation process was initiated from the very first moment of irradiation, and it produced ketones, acids, esters (intramolecular and of acetate type), peracids, peresters, hydroperoxides, and alcohols. The molecular weight values and gel number values, which were established as well, pointed out that oxidation was accompanied by cracking of polymer macromolecules, and also by polymer crosslinking to a limited degree. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Prostate-derived sterile 20-like kinases (PSKs) 1-α, 1-β, and 2 are members of the germinal-center kinase-like sterile 20 family of kinases. Previous work has shown that PSK 1-α binds and stabilizes microtubules whereas PSK2 destabilizes microtubules. Here, we have investigated the activation and autophosphorylation of endogenous PSKs and show that their catalytic activity increases as cells accumulate in G(2)/M and declines as cells exit mitosis. PSKs are stimulated in synchronous HeLa cells as they progress through mitosis, and these proteins are activated catalytically during each stage of mitosis. During prophase and metaphase activated PSKs are located in the cytoplasm and at the spindle poles, and during telophase and cytokinesis stimulated PSKs are present in trans-Golgi compartments. In addition, small interfering RNA (siRNA) knockdown of PSK1-α/β or PSK2 expression inhibits mitotic cell rounding as well as spindle positioning and centralization. These results show that PSK catalytic activity increases during mitosis and suggest that these proteins can contribute functionally to mitotic cell rounding and spindle centralization during cell division.

The preliminary investigation of the effects of using iron(III) acetylacetonate (acacFe) in low density polyethylene (PE-LD) composites with magnesium hydroxide (MH) after different modifications on flammability was conducted. The results showed that employment of a small amount of acacFe in composites with MH, modified with a silane compound (Magnifin H10A) may reduce the total burning times for a whole series of samples in the vertical position and it may increase tensile strain at break (e B ) of samples.

Background Research is still being conducted in order to determine the mechanisms responsible for the initiation of rheumatoid arthritis (RA) as well as for its persistence and progression. Objectives The aim of this work was to establish the expression of the signal transducer and activator of transcription (STAT) transcription factors and the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) transcription factor in peripheral blood leukocytes and synovial fluid cells. The correlations between the activation level of the transcription factors and the activity of the disease were also analyzed. Material and methods In total, the study included 34 RA patients and 19 healthy individuals as controls. The expression of NFκB, STAT1, STAT3, STAT4, STAT5 and STAT6 in peripheral blood leukocytes and synovial fluid cells was established. The immunocytochemistry method was used to determine the degree of activation of STAT and NF-κB transcription factors. For the location of the factors, primary polyclonal anti-STATs and monoclonal anti-NF-κB antibodies were used. Results The expression of STAT1, STAT3, STAT4, STAT5, STAT6 and NFκB was significantly higher in the group of RA patients than in the controls. No statistically significant differences were found between the expression of STATs in peripheral blood leukocytes and synovial fluid cells. Conclusions In comparison with the control group, the expression of the STAT and NFκB transcription factors in RA patients was higher, which may be helpful in better understanding the etiopathogenesis of the disease in the future, and may potentially have important therapeutic implications.

Publikacja przynosi różne spojrzenia na zjawisko zaangażowania (się) / angażowania (się) w dydaktyce. Znajdziemy tu teksty ujmujące ów proces z teoretycznej bądź historycznej perspektywy, a także takie, których autorzy ukazują realne – wypływające z ich dydak¬tycznych doświadczeń – efekty stosowania twórczych rozwiązań edukacyjnych w motywowaniu studentów. Jakie to metody? Stoliki negocjacyjne, audiodeskrypcja, personalizacja zadań, realizacja projektu – to niektóre z propozycji. Autorzy piszą nie tylko o konieczności angażowania studentów w proces edukacyjny. Zwracają też uwagę na konieczność rozbudzania i podtrzymywania pasji dydaktycznej i badawczej zarówno u nauczycieli, jak i u studentów. The progress of civilization and the economic, social, and cultural transformations resulting from it are behind the changes occurring in people and influencing their oppor¬tunities and needs. Those changes are triggered by the people striving to adapt to the new situation by acquiring knowledge, experiences, and skills, which help them find them¬selves in the existing reality. It is that need to acquire knowledge and the ability to employ it in life, which in effect leads to changes occurring in the entire personality, that is one of the basic human needs described by the psychologists and one of the key goals of the education process. Teacher responsible for organizing that process first of all should be acquainted with characteristics of the target group, for which all the didactic activities need to be adapted. In case of a university teacher the target group are students, who are on the verge of their transition from adolescence to early adulthood. Because the students employ various learning models, work with such a target group requires the teacher to be able to combine the knowledge from pedagogy and andragogics areas. The teacher working with adults needs to be familiar with such tools as knowledge about developing the objectives and defining education results, selection of content that is interesting to the students and of teaching aids adequate to the needs, levels, and abilities of the students. Teacher work¬ing with adults must also know what kind of teaching methods ought to be used in adult education, what methods are suitable for a given type of classes, and what methods help to activate all the senses, which in turn raises the effectiveness of the didactic process he/ she organizes. Teacher then ought to be competent in the content, pedagogy, didactics, and methodology areas, as well as should be able to combine those competences with the knowledge from the area of andragogics.

Modification of low-density polyethylene (PE-LD) with allylurea (AM) by reactive extrusion in the presence of dicumyl peroxide (DCP) as radical initiator of the expected grafting reaction has been described. Modification has been done in order to increase PE-LD susceptibility to degradation in the environment. FT-IR investigations showed the probability of the intermolecular AM condensation during processing at the conditions applied (Figs. 2, 3). The changes found should not impede the process of AM grafting. The slip of extruder screw, caused by AM, has been limited by addition of silica (K) to the composition. Composition properties have been studied in wide range of concentrations of silica (up to 8 wt. %), allylurea (up to 8 wt. %) and peroxide (up to 0.6 wt. %). The material showing good breaking strength was obtained when silica content in the composition (equal to AM content) was 3 wt. %. Gel number of various compositions was also determined. The samples obtained at small amounts of DCP, up to 0.2 wt. %, showed required low crosslinking degree (Table 1). FT-IR analysis suggests the partial grafting of allylurea onto PE chains (Table 2).

The aims of this study were to determine the proportion of rheumatoid arthritis (RA) patients attending hospital in whom amyloid deposits were present in abdominal fat aspiration (AFA) samples, and to assess possible risk factors for amyloid development in RA. One -hundred and twenty-one patients (16 males, 105 females) with RA referred to the Department of Rheumatology in Wroclaw between 1996 and 2001 were studied regardless of RA duration or laboratory findings. Abdominal subcutaneous fine-needle aspiration was performed, and samples of adipose tissue stained with alkaline Congo red then examined by polarized light microscopy. The presence or absence of amyloid fat deposits (AFD) was determined according to whether typical apple-green birefringence was observed. Amyloid deposits were found in 35 (29%) patients. Amyloidosis was significantly more common in males and in patients with longer disease duration. Patients with AFD had previously undergone less treatment with disease-modifying antirheumatic drugs (DMARDs) than those without AFD, and significantly fewer patients with AFD had previously taken methotrexate than those without AFD (25% vs 45%; p