400 research outputs found

    Separating neural oscillations from aperiodic 1/f activity: Challenges and recommendations

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    Electrophysiological power spectra typically consist of two components: An aperiodic part usually following an 1/f power law [Formula: see text] and periodic components appearing as spectral peaks. While the investigation of the periodic parts, commonly referred to as neural oscillations, has received considerable attention, the study of the aperiodic part has only recently gained more interest. The periodic part is usually quantified by center frequencies, powers, and bandwidths, while the aperiodic part is parameterized by the y-intercept and the 1/f exponent [Formula: see text]. For investigation of either part, however, it is essential to separate the two components. In this article, we scrutinize two frequently used methods, FOOOF (Fitting Oscillations & One-Over-F) and IRASA (Irregular Resampling Auto-Spectral Analysis), that are commonly used to separate the periodic from the aperiodic component. We evaluate these methods using diverse spectra obtained with electroencephalography (EEG), magnetoencephalography (MEG), and local field potential (LFP) recordings relating to three independent research datasets. Each method and each dataset poses distinct challenges for the extraction of both spectral parts. The specific spectral features hindering the periodic and aperiodic separation are highlighted by simulations of power spectra emphasizing these features. Through comparison with the simulation parameters defined a priori, the parameterization error of each method is quantified. Based on the real and simulated power spectra, we evaluate the advantages of both methods, discuss common challenges, note which spectral features impede the separation, assess the computational costs, and propose recommendations on how to use them

    Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

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    <p>Abstract</p> <p>Background</p> <p>Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (<it>PLK1</it>) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy.</p> <p>Methods</p> <p>We examined the expression of <it>PLK1 </it>mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi) or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting <it>PLK1 </it>mRNA on tumor-initiating cells was evaluated using tumor sphere assays.</p> <p>Results</p> <p>Analysis of gene expression in two independent cohorts revealed that <it>PLK1 </it>mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y)-box 2 (<it>SOX2</it>) mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells.</p> <p>Conclusions</p> <p>Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of medulloblastoma that warrants further investigation.</p

    The Aussie, 1918-1931: cartoons, digger remembrance and First World War identity

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    Feelings of community, cultural definition and memory were kept alive through the soldiers’ mass circulation tabloid, the Aussie, examined here in the light of theorization of memory and representation, applied to both text and cartoons. The publication’s aim for veterans’ values to become shared national values is analysed in the light of its high profile usage of soft cartoon humour and also of nostalgia – highlighting the limitations as well as the effectiveness in terms of Australia’s evolving national identity. When the post-war economic situation worsened, deeper issues of national tension were glossed over by the use of scapegoats such as ‘profiteers’ and ‘lazy workers’. The armed forces were obliged to take on a political role of lobbying for their cause, but the Aussie as ‘cheerful friend’ experienced its own identity crisis that proved to be terminal

    Effect of vitamin E (Tri E®) on antioxidant enzymes and DNA damage in rats following eight weeks exercise

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    <p>Abstract</p> <p>Background</p> <p>Exercise is beneficial to health, but during exercise the body generates reactive oxygen species (ROS) which are known to result in oxidative stress. The present study analysed the effects of vitamin E (Tri E<sup>®</sup>) on antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (Cat) activity and DNA damage in rats undergoing eight weeks exercise.</p> <p>Methods</p> <p>Twenty four <it>Sprague-Dawley </it>rats (weighing 320-370 gm) were divided into four groups; a control group of sedentary rats which were given a normal diet, second group of sedentary rats with oral supplementation of 30 mg/kg/d of Tri E<sup>®</sup>, third group comprised of exercised rats on a normal diet, and the fourth group of exercised rats with oral supplementation of 30 mg/kg/d of Tri E<sup>®</sup>. The exercising rats were trained on a treadmill for 30 minutes per day for 8 weeks. Blood samples were taken before and after 8 weeks of the study to determine SOD, GPx, Cat activities and DNA damage.</p> <p>Results</p> <p>SOD activity decreased significantly in all the groups compared to baseline, however both exercised groups showed significant reduction in SOD activity as compared to the sedentary groups. Sedentary control groups showed significantly higher GPx and Cat activity compared to baseline and exercised groups. The supplemented groups, both exercised and non exercised groups, showed significant decrease in Cat activity as compared to their control groups with normal diet. DNA damage was significantly higher in exercising rats as compared to sedentary control. However in exercising groups, the DNA damage in supplemented group is significantly lower as compared to the non-supplemented group.</p> <p>Conclusions</p> <p>In conclusion, antioxidant enzymes activity were generally reduced in rats supplemented with Tri E<sup>® </sup>probably due to its synergistic anti-oxidative defence, as evidenced by the decrease in DNA damage in Tri E<sup>® </sup>supplemented exercise group.</p

    γ-H2AX Kinetics as a Novel Approach to High Content Screening for Small Molecule Radiosensitizers

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    Persistence of γ-H2AX after ionizing radiation (IR) or drug therapy is a robust reporter of unrepaired DNA double strand breaks in treated cells.DU-145 prostate cancer cells were treated with a chemical library ±IR and assayed for persistence of γ-H2AX using an automated 96-well immunocytochemistry assay at 4 hours after treatment. Hits that resulted in persistence of γ-H2AX foci were tested for effects on cell survival. The molecular targets of hits were validated by molecular, genetic and biochemical assays and in vivo activity was tested in a validated Drosophila cancer model.We identified 2 compounds, MS0019266 and MS0017509, which markedly increased persistence of γ-H2AX, apoptosis and radiosensitization in DU-145 cells. Chemical evaluation demonstrated that both compounds exhibited structurally similar and biochemical assays confirmed that these compounds inhibit ribonucleotide reductase. DNA microarray analysis and immunoblotting demonstrates that MS0019266 significantly decreased polo-like kinase 1 gene and protein expression. MS0019266 demonstrated in vivo antitumor activity without significant whole organism toxicity.MS0019266 and MS0017509 are promising compounds that may be candidates for further development as radiosensitizing compounds as inhibitors of ribonucleotide reductase

    Dietary Supplements and Sports Performance: Introduction and Vitamins

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    Sports success is dependent primarily on genetic endowment in athletes with morphologic, psychologic, physiologic and metabolic traits specific to performance characteristics vital to their sport. Such genetically-endowed athletes must also receive optimal training to increase physical power, enhance mental strength, and provide a mechanical advantage. However, athletes often attempt to go beyond training and use substances and techniques, often referred to as ergogenics, in attempts to gain a competitive advantage. Pharmacological agents, such as anabolic steroids and amphetamines, have been used in the past, but such practices by athletes have led to the establishment of anti-doping legislation and effective testing protocols to help deter their use. Thus, many athletes have turned to various dietary strategies, including the use of various dietary supplements (sports supplements), which they presume to be effective, safe and legal
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