Ischemic Conditioning Increases Strength and Volitional Activation of Paretic Muscle in Chronic Stroke: A Pilot Study

7siIschemic conditioning (IC) on the arm or leg has emerged as an intervention to improve strength and performance in healthy populations, but the effects on neurologic populations are unknown. The purpose of this study was to quantify the effects of a single session of IC on knee extensor strength and muscle activation in chronic stroke survivors. Maximal knee extensor torque measurements and surface EMG were quantified in 10 chronic stroke survivors (>1 year post-stroke) with hemiparesis before and after a single session of IC or Sham on the paretic leg. IC consisted of five minutes of compression with a proximal thigh cuff (inflation pressure = 225 mmHg for IC or 25 mmHg for Sham) followed by five minutes of rest. This was repeated five times. Maximal knee extensor strength, EMG magnitude, and motor unit firing behavior were measured before and immediately after IC or Sham. IC increased paretic leg strength by 10.6plus minus8.5 Nm while no difference was observed in the Sham group (change in Sham = 1.3plus minus2.9 Nm; p = 0.001 IC vs. Sham). IC-induced increases in strength were accompanied by a 31plus minus15% increase in the magnitude of muscle EMG during maximal contractions and a 5% decrease in motor unit recruitment thresholds during sub-maximal contractions. Individuals who had the most asymmetry in strength between their paretic and non-paretic legs had the largest increases in strength (r2= 0.54). This study provides evidence that a single session of IC can increase strength through improved muscle activation in chronic stroke survivors.openembargoed_20190204Hyngstrom, Allison S; Murphy, Spencer A; Nguyen, Jennifer; Schmit, Brian D; Negro, Francesco; Gutterman, David D; Durand, Matthew JHyngstrom, Allison S; Murphy, Spencer A; Nguyen, Jennifer; Schmit, Brian D; Negro, Francesco; Gutterman, David D; Durand, Matthew

Seed Mucilage Improves Seedling Emergence of a Sand Desert Shrub

The success of seedling establishment of desert plants is determined by seedling emergence response to an unpredictable precipitation regime. Sand burial is a crucial and frequent environmental stress that impacts seedling establishment on sand dunes. However, little is known about the ecological role of seed mucilage in seedling emergence in arid sandy environments. We hypothesized that seed mucilage enhances seedling emergence in a low precipitation regime and under conditions of sand burial. In a greenhouse experiment, two types of Artemisia sphaerocephala achenes (intact and demucilaged) were exposed to different combinations of burial depth (0, 5, 10, 20, 40 and 60 mm) and irrigation regimes (low, medium and high, which simulated the precipitation amount and frequency in May, June and July in the natural habitat, respectively). Seedling emergence increased with increasing irrigation. It was highest at 5 mm sand burial depth and ceased at burial depths greater than 20 mm in all irrigation regimes. Mucilage significantly enhanced seedling emergence at 0, 5 and 10 mm burial depths in low irrigation, at 0 and 5 mm burial depths in medium irrigation and at 0 and 10 mm burial depths in high irrigation. Seed mucilage also reduced seedling mortality at the shallow sand burial depths. Moreover, mucilage significantly affected seedling emergence time and quiescence and dormancy percentages. Our findings suggest that seed mucilage plays an ecologically important role in successful seedling establishment of A. sphaerocephala by improving seedling emergence and reducing seedling mortality in stressful habitats of the sandy desert environment

Avicin D, a Plant Triterpenoid, Induces Cell Apoptosis by Recruitment of Fas and Downstream Signaling Molecules into Lipid Rafts

Avicins, a family of triterpene electrophiles originally identified as potent inhibitors of tumor cell growth, have been shown to be pleiotropic compounds that also possess antioxidant, anti-mutagenic, and anti-inflammatory activities. We previously showed that Jurkat cells, which express a high level of Fas, are very sensitive to treatment with avicins. Thus, we hypothesized that avicins may induce cell apoptosis by activation of the Fas pathway. By using a series of cell lines deficient in cell death receptors, we demonstrated that upon avicin D treatment, Fas translocates to the cholesterol- and sphingolipid-enriched membrane microdomains known as lipid rafts. In the lipid rafts, Fas interacts with Fas-associated death domain (FADD) and Caspase-8 to form death-inducing signaling complex (DISC) and thus mediates cell apoptosis. Interfering with lipid raft organization by using a cholesterol-depleting compound, methyl-β-cyclodextrin, not only prevents the clustering of Fas and its DISC complex but also reduces the sensitivity of the cells to avicin D. Avicin D activates Fas pathways independent of the association between extracellular Fas ligands and Fas receptors. A deficiency in Fas and its downstream signaling molecules leads to the resistance of the cells to avicin D treatment. Taken together, our results demonstrate that avicin D triggers the redistribution of Fas in the membrane lipid rafts, where Fas activates receptor-mediated cell death

Influence of IFN-gamma and its receptors in human breast cancer

<p>Abstract</p> <p>Background</p> <p>Interferons are a group of proteins that trigger multiple responses including prevention of viral replication, inhibition of cell growth, and modulation of cell differentiation. In different mammary carcinoma cell lines IFNγ induces growth arrest at mid-G1. At the present there are no <it>in vivo </it>studies in human breast. The aim of this study was to investigate the expression patterns of IFNγ and its two receptors (IFNγ-Rα and IFNγ-Rβ) by Western blot and immunohistochemistry, in order to elucidate its role in the different types of human breast cancer (<it>in situ </it>and infiltrative).</p> <p>Methods</p> <p>Immunohistochemical and semiquantitative study of IFNγ, its receptors types (IFNγ-Rα and IFNγ-Rβ), cell proliferation (proliferating cell nuclear antigen, also named PCNA), and apoptosis (TUNEL method) was carried between the three breast groups (fibrocystic lesions, <it>in situ</it> tumors and infiltrating tumors).</p> <p>Results</p> <p>In the three groups of patients, IFNγ and IFNγ-Rα immunoreactions appeared in the cytoplasm while IFNγ-Rβ also was found in the nucleus. The optical density to IFNγ was higher in <it>in situ </it>carcinoma than in benign and infiltrating tumors. When we observed IFNγ-Rα, the optical density was lower in infiltrating carcinoma than in benign and <it>in situ </it>tumors (the higher density). To IFNγ-Rβ, the optical density was similar in the three group samples. In tumor samples PCNA and TUNEL index was significantly higher; than in benign diseases. PCNA index increased with the malignance. No significant differences were found between cancer types to TUNEL. IFNγ could be a potential therapeutic tool in breast cancer. However, tumor cells are able to escape from the control of this cytokine in the early tumor stages; this is probably due to a decreased expression of IFNγ, or also to an alteration of either its receptors or some transduction elements.</p> <p>Conclusion</p> <p>We conclude that the decrease in the % positive samples that expressed IFNγ and IFNγ-Rα together with the nuclear localization of IFNγ-Rβ, could be a tumoral cell response, although perhaps insufficient to inhibit the uncontrolled cell proliferation. Perhaps, IFNγ might be unable to activate p21 to stop the cell cycle, suggesting a possible participation in breast cancer development.</p

An orally available, small-molecule interferon inhibits viral replication

Most acute hepatitis C virus (HCV) infections become chronic and some progress to liver cirrhosis or hepatocellular carcinoma. Standard therapy involves an interferon (IFN)-α-based regimen, and efficacy of therapy has been significantly improved by the development of protease inhibitors. However, several issues remain concerning the injectable form and the side effects of IFN. Here, we report an orally available, small-molecule type I IFN receptor agonist that directly transduces the IFN signal cascade and stimulates antiviral gene expression. Like type I IFN, the small-molecule compound induces IFN-stimulated gene (ISG) expression for antiviral activity in vitro and in vivo in mice, and the ISG induction mechanism is attributed to a direct interaction between the compound and IFN-α receptor 2, a key molecule of IFN-signaling on the cell surface. Our study highlights the importance of an orally active IFN-like agent, both as a therapy for antiviral infections and as a potential IFN substitute

A cell culture model using rat coronary artery adventitial fibroblasts to measure collagen production

<p>Abstract</p> <p>Background</p> <p>We have developed a rat cell model for studying collagen type I production in coronary artery adventitial fibroblasts. Increased deposition of adventitial collagen type I leads to stiffening of the blood vessel, increased blood pressure, arteriosclerosis and coronary heart disease. Although the source and mechanism of collagen deposition is yet unknown, the adventitia appears to play a significant role. To demonstrate the application of our cell model, cultured adventitial fibroblasts were treated with sex hormones and the effect on collagen production measured.</p> <p>Methods</p> <p>Hearts (10–12 weeks) were harvested and the left anterior descending coronary artery (LAD) was isolated and removed. Tissue explants were cultured and cells (passages 2–4) were confirmed as fibroblasts using immunohistochemistry. Optimal conditions were determined for cell tissue harvest, timing, proliferation and culture conditions. Fibroblasts were exposed to 10^-7M testosterone or 10^-7M estrogen for 24 hours and either immunostained for collagen type I or subjected to ELISA.</p> <p>Results</p> <p>Results showed increased collagen staining in fibroblasts treated with testosterone compared to control and decreased staining with estrogen. ELISA results showed that testosterone increased collagen I by 20% whereas estrogen decreased collagen I by 15%.</p> <p>Conclusion</p> <p>Data demonstrates the usefulness of our cell model in studying the specific role of the adventitia apart from other blood vessel tissue in rat coronary arteries. Results suggest opposite effects of testosterone and estrogen on collagen synthesis in the rat coronary artery adventitial fibroblasts.</p

Adam Sandler as (questionable) masculine ‘role model’: towards an analysis of disgust and violence in Adam Sandler's comedian comedy

© 2018 Informa UK Limited, trading as Taylor & Francis Group Adam Sandler's film work has been critically vilified and paid little attention by academics. This article suggests that his work justifies sustained academic attention, yet I conclude that he offers questionable masculine role models dependent on masculinity being asserted via ambivalent dis-identification with gay men and women. I argue this case via critique of the most sustained analyses of his workand via close readings of aspects of Sandler's films. I dispute Chapman's contextualisation of Sandler's film comedies in relation to thinking about masculinity and gay men. These changes have arisen in response to feminism and the lesbian and gay movement. I argue that Chapman's contextualisation of, and the ambiguities of Sandler's engagement with, feminism and gay men needs more critical attention. Further, I argue that we should actively read Sandler's films using Seidman's idea of comedian comedy and that focusing attention on such comedies’ tensions with narrative film enable us to direct our critical attention on the ambivalences present in Sandler's movies. His films show resistance to relinquishing some privileges of dominant forms of masculinity (physical violence) and demonstrate disgust withthe sexuality, bodies and behaviour of gay men

Butyrate augments interferon-α-induced S phase accumulation and persistent tyrosine phosphorylation of cdc2 in K562 cells

Interferon-α (IFN-α) is a clinically useful cytokine for treatment of a variety of cancers, including chronic myelocytic leukaemia (CML). Most CML cells are sensitive to IFN-α; however, its biological effects on leukaemic cells are incompletely characterized. Here, we provide evidence that IFN-α induces a significant increase in the S phase population in human CML leukaemic cell line, K562, and that the S phase accumulation was augmented by sodium butyrate. In contrast, neither sodium butyrate alone, nor sodium butyrate plus IFN-γ, affected the cell cycle in K562 cells. These data suggest that the effect of sodium butyrate depended upon IFN-α-mediated signalling. The ability of leukaemic cells to exhibit the S phase accumulation after stimulation by IFN-α plus sodium butyrate correlated well with persistent tyrosine phosphorylation of cdc2, whereas treatment with IFN-γ plus sodium butyrate did not affect its phosphorylation levels. Considering that dephosphorylation of cdc2 leads to entry to the M phase, the persistent tyrosine phosphorylation of cdc2 may be associated with the S phase accumulation induced by IFN-α and sodium butyrate. In addition, another human CML leukaemic cell line, MEG-01, also showed the S phase accumulation after stimulation with IFN-α plus sodium butyrate. Taken together, our studies reveal a novel effect of sodium butyrate on the S phase accumulation and suggest its clinical application for a combination therapy with IFN-α, leading to a great improvement of clinical effects of IFN-α against CML cells. © 1999 Cancer Research Campaig