Reactive Oxygen Species-Mediated Neurodegeneration is Independent of the Ryanodine Receptor in Caenorhabditis elegans

Despite the significant impacts on human health caused by neurodegeneration, our understanding of the degeneration process is incomplete. The nematode Caenorhabditis elegans is emerging as a genetic model organism well suited for identification of conserved cellular mechanisms and molecular pathways of neurodegeneration. Studies in the worm have identified factors that contribute to neurodegeneration, including excitotoxicity and stress due to reactive oxygen species (ROS). Disruption of the gene unc-68, which encodes the ryanodine receptor, abolishes excitotoxic cell death, indicating a role for calcium (Ca2+) signaling in neurodegeneration. We tested the requirement for unc-68 in ROS-mediated neurodegeneration using the genetically encoded photosensitizer KillerRed. Upon illumination of KillerRed expressing animals to produce ROS, we observed similar levels of degeneration in wild-type and unc-68 mutant strains. Our results indicate that ROS-mediated cell death is independent of unc-68 and suggest multiple molecular pathways of neurodegeneration

Biopedagogies and Indigenous knowledge: examining sport for development and peace for urban Indigenous young women in Canada and Australia

This paper uses transnational postcolonial feminist participatory action research (TPFPAR) to examine two sport for development and peace (SDP) initiatives that focus on Indigenous young women residing in urban areas, one in Vancouver, Canada, and one in Perth, Australia. We examine how SDP programs that target urban Indigenous young women and girls reproduce the hegemony of neoliberalism by deploying biopedagogies of neoliberalism to \u27teach\u27 Indigenous young women certain education and employment skills that are deemed necessary to participate in competitive capitalism. We found that activities in both programs were designed to equip the Indigenous girls and young women with individual attributes that would enhance their chances of future success in arenas valued by neoliberal capitalism: Eurocentric employment, post-secondary education and healthy active living. These forms of \u27success\u27 fall within neoliberal logic, where the focus is on the individual being able to provide for oneself. However, the girls and young women we interviewed argued that their participation in the SDP programs would help them change racist and sexist stereotypes about their communities and thereby challenged negative stereotypes. Thus, it is possible that these programs, despite their predominant use of neoliberal logic and biopedagogies, may help to prepare the participants to more successfully negotiate Eurocentric institutions, and through this assist them participants in contributing to social change. Nevertheless, based on our findings, we argue that SDP programs led by Indigenous peoples that are fundamentally shaped by Indigenous voices, epistemologies, concerns and standpoints would provide better opportunities to shake SDP\u27s current biopedagogical foundation. We conclude by suggesting that a more radical approach to SDP, one that fosters Indigenous self-determination and attempts to disrupt dominant relations of power, could have difficulty in attracting the sort of corporate donors who currently play such important roles in the current SDP landscape

Sport, Gender and Development : Intersections, Innovations and Future Trajectories

The ebook edition of this title is Open Access, thanks to Knowledge Unlatched funding, and freely available to read online. In a context where striving for gender equity in relation to achieving the UN Sustainable Development Goals seems more pressing than ever before, Sport, Gender and Development: Intersections, Innovations and Future Trajectories bring together an exploration of sport feminisms to offer new approaches to research on Sport for Development and Peace (SDP) in global and local contexts. Including postcolonial and decolonial feminist lenses by drawing upon fieldwork with organizations and individuals in Afghanistan, Uganda, Nicaragua, and India, Sport, Gender and Development reveals the complexities of development and gender discourses and how they operate on and through researchers, practitioners, and participants\u27 bodies. Delving into a thoughtful engagement with the (dis)connections and comparisons across these diverging contexts, this book offers a critically reflexive account of what is transpiring in the transnational sport, gender, and development field, while remaining sensitive to the importance of community context and local iterations. Taking up emerging and contemporary feminist issues in sport-related international development, this book advances empirical, conceptual, and theoretical developments in the sport, gender, and development. Read the full book at https://www.emerald.com/insight/publication/doi/10.1108/9781838678630.https://digitalcommons.otterbein.edu/fac_bk/1006/thumbnail.jp

Проблеми та можливості споживання енергії в Україні

Проаналізовано споживання енергії в різних секторах економіки й подано модель визначення потенціалу зниження споживання енергії в Україні. Ключові слова: енергоефективність, енергозбереження, енергоємність, енергоспоживання, потенціал зменшення споживання енергії.Проанализированы потребления энергии в различных секторах экономики и представлена модель определения потенциала снижения потребления энергии в Украине. Ключевые слова: энергоэффективность, энергосбережение, энергоемкость, энергопотребление, потенциал уменьшения потребления энергии.The paper analyses energy consumption in different economic sectors and presents the model of determining the potential of reducing energy consumption in Ukraine. Keywords: energy efficiency, energy saving, energy intensity, energy waste, energy consumption, potential of reducing energy consumption

Evaluating the effectiveness of Leadership Development in Healthcare

Organisations across both public and commercial sectors consider leadership to be important but the evidence for a link to organisational performance is complicated. Nonetheless, much of the literature on leadership development indicates that the hallmarks of successful leadership development programmes are those that are clearly and transparently linked to strategic organisational aims and objectives. in the context of a financially challenged and publicly scrutinised NHS, this led to the development of the LeaDER framework. The LeaDER framework combines Theory Based Evaluation (TBE), Realistic Evaluation (RE) and the Kirkpatrick model of evaluation in examining the context, Theories of Change (ToC) and emergent outcomes in leadership development as well as hypothesising about anticipated and measurable impacts. This current research project sought to review the national adoption of this model, to make suggestions for its further improvement and offer insights into the nature and effectiveness of leadership development

The Radiated Energy Budget of Chromospheric Plasma in a Major Solar Flare Deduced From Multi-Wavelength Observations

This paper presents measurements of the energy radiated by the lower solar atmosphere, at optical, UV, and EUV wavelengths, during an X-class solar flare (SOL2011-02-15T01:56) in response to an injection of energy assumed to be in the form of nonthermal electrons. Hard X-ray observations from RHESSI were used to track the evolution of the parameters of the nonthermal electron distribution to reveal the total power contained in flare accelerated electrons. By integrating over the duration of the impulsive phase, the total energy contained in the nonthermal electrons was found to be $>2\times10^{31}$ erg. The response of the lower solar atmosphere was measured in the free-bound EUV continua of H I (Lyman), He I, and He II, plus the emission lines of He II at 304\AA\ and H I (Ly$\alpha$) at 1216\AA\ by SDO/EVE, the UV continua at 1600\AA\ and 1700\AA\ by SDO/AIA, and the WL continuum at 4504\AA, 5550\AA, and 6684\AA, along with the Ca II H line at 3968\AA\ using Hinode/SOT. The summed energy detected by these instruments amounted to $\sim3\times10^{30}$ erg; about 15% of the total nonthermal energy. The Ly$\alpha$ line was found to dominate the measured radiative losses. Parameters of both the driving electron distribution and the resulting chromospheric response are presented in detail to encourage the numerical modelling of flare heating for this event, to determine the depth of the solar atmosphere at which these line and continuum processes originate, and the mechanism(s) responsible for their generation.Comment: 14 pages, 18 figures. Accepted for publication in Astrophysics Journa

Simulations of the Mg II k and Ca II 8542 lines from an AlfvÉn Wave-heated Flare Chromosphere

We use radiation hydrodynamic simulations to examine two models of solar flare chromospheric heating: Alfven wave dissipation and electron beam collisional losses. Both mechanisms are capable of strong chro- ´ mospheric heating, and we show that the distinctive atmospheric evolution in the mid-to-upper chromosphere results in Mg ii k-line emission that should be observably different between wave-heated and beam-heated simulations. We also present Ca ii 8542Å profiles which are formed slightly deeper in the chromosphere. The Mg ii k-line profiles from our wave-heated simulation are quite different from those from a beam-heated model and are more consistent with IRIS observations. The predicted differences between the Ca ii 8542Å in the two models are small. We conclude that careful observational and theoretical study of lines formed in the mid-toupper chromosphere holds genuine promise for distinguishing between competing models for chromospheric heating in flares

Anti-tumor effects of retinoids combined with trastuzumab or tamoxifen in breast cancer cells: induction of apoptosis by retinoid/trastuzumab combinations

INTRODUCTION: HER2 and estrogen receptor (ER) are important in breast cancer and are therapeutic targets of trastuzumab (Herceptin) and tamoxifen, respectively. Retinoids inhibit breast cancer growth, and modulate signaling by HER2 and ER. We hypothesized that treatment with retinoids and simultaneous targeting of HER2 and/or ER may have enhanced anti-tumor effects. METHODS: The effects of retinoids combined with trastuzumab or tamoxifen were examined in two human breast cancer cell lines in culture, BT474 and SKBR3. Assays of proliferation, apoptosis, differentiation, cell cycle distribution, and receptor signaling were performed. RESULTS: In HER2-overexpressing/ER-positive BT474 cells, combining all-trans retinoic acid (atRA) with tamoxifen or trastuzumab synergistically inhibited cell growth, and altered cell differentiation and cell cycle. Only atRA/trastuzumab-containing combinations induced apoptosis. BT474 and HER2-overexpressing/ER-negative SKBR3 cells were treated with a panel of retinoids (atRA, 9-cis-retinoic acid, 13-cis-retinoic acid, or N-(4-hydroxyphenyl) retinamide (fenretinide) (4-HPR)) combined with trastuzumab. In BT474 cells, none of the single agents except 4-HPR induced apoptosis, but again combinations of each retinoid with trastuzumab did induce apoptosis. In contrast, the single retinoid agents did cause apoptosis in SKBR3 cells; this was only modestly enhanced by addition of trastuzumab. The retinoid drug combinations altered signaling by HER2 and ER. Retinoids were inactive in trastuzumab-resistant BT474 cells. CONCLUSIONS: Combining retinoids with trastuzumab maximally inhibits cell growth and induces apoptosis in trastuzumab-sensitive cells. Treatment with such combinations may have benefit for breast cancer patients