Newly Developed Mg2+–Selective Fluorescent Probe Enables Visualization of Mg2+ Dynamics in Mitochondria

Mg2+ plays important roles in numerous cellular functions. Mitochondria take part in intracellular Mg2+ regulation and the Mg2+ concentration in mitochondria affects the synthesis of ATP. However, there are few methods to observe Mg2+ in mitochondria in intact cells. Here, we have developed a novel Mg2+–selective fluorescent probe, KMG-301, that is functional in mitochondria. This probe changes its fluorescence properties solely depending on the Mg2+ concentration in mitochondria under physiologically normal conditions. Simultaneous measurements using this probe together with a probe for cytosolic Mg2+, KMG-104, enabled us to compare the dynamics of Mg2+ in the cytosol and in mitochondria. With this method, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP)–induced Mg2+ mobilization from mitochondria to the cytosol was visualized. Although a FCCP–induced decrease in the Mg2+ concentration in mitochondria and an increase in the cytosol were observed both in differentiated PC12 cells and in hippocampal neurons, the time-courses of concentration changes varied with cell type. Moreover, the relationship between mitochondrial Mg2+ and Parkinson's disease was analyzed in a cellular model of Parkinson's disease by using the 1-methyl-4-phenylpyridinium ion (MPP+). A gradual decrease in the Mg2+ concentration in mitochondria was observed in response to MPP+ in differentiated PC12 cells. These results indicate that KMG-301 is useful for investigating Mg2+ dynamics in mitochondria. All animal procedures to obtain neurons from Wistar rats were approved by the ethical committee of Keio University (permit number is 09106-(1))

Inhibition of Soluble Tumor Necrosis Factor Ameliorates Synaptic Alterations and Ca2+ Dysregulation in Aged Rats

The role of tumor necrosis factor α (TNF) in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1) are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2) in aged (22 months) but not young adult (6 months) Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4–6 week) intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits TNFR1 signaling. Aged rats treated with XPro1595 showed improved Morris Water Maze performance, reduced microglial activation, reduced susceptibility to hippocampal long-term depression, increased protein levels for the GluR1 type glutamate receptor, and lower L-type voltage sensitive Ca2+ channel (VSCC) activity in hippocampal CA1 neurons. The results suggest that diverse functional changes associated with brain aging may arise, in part, from selective alterations in TNF signaling

Global Climate Justice Activism: “The New Protagonists” and their Projects for a Just Transition

The contributors to this volume have provided ample evidence to support calls for fundamental, transformative change in the world-system. If there remained any doubts, their analyses show that the capitalist world-system threatens not only the well-being of a majority of the world’s people, but also the very survival of our planet. Indeed, the urgency of the ecological and economic conditions that many people now face and the immense inequalities that have become more entrenched require that scholars become more consciously engaged in the work of advancing social transformation. Revolutionary change is emergent in movement spaces where people have long been working to develop shared analyses and cultivate collective power and agency by building unity among a diverse array of activists, organizations, and movements. We discuss three examples of transformative projects that are gaining increased visibility and attention: food sovereignty, solidarity economies, and Human Rights Communities. If widely adopted, these projects would undermine the basic processes necessary for the capitalist world-system to function. With these projects, defenders of environmental and social justice not only work to prevent their own (further) dispossession by denying capital its ability to continue appropriating labor and resources from working people and communities, but they also help deepen the existing systemic crisis while sowing the seeds of a new social order

Capital social y promoción de la salud en América Latina Social capital and health promotion in Latin America

América Latina enfrenta problemáticas de desarrollo y salud comunes. La equidad y la superación de la pobreza son cruciales en la búsqueda de soluciones integrales y de alto impacto. El artículo analiza el concepto de capital social, su relación con salud, sus limitaciones y potencialidades, desde una perspectiva de desarrollo comunitario y promoción de salud en América Latina. También, se identifican desafíos prioritarios, como la medición y fortalecimiento del capital social. Se discute cómo y por qué el capital social pudiera ser crítico en una estrategia global de promoción de la salud, donde el empoderamiento y la participación comunitaria, el trabajo interdisciplinario e intersectorial permitirían avanzar en los objetivos de salud pública y en la concreción de un cambio social sustentable. Igualmente, se identifican algunas de las potenciales limitaciones del concepto de capital social en el contexto de promoción de la salud en América Latina.<br>Latin America faces common development and health problems and equity and overcoming poverty are crucial in the search for comprehensive and high impact solutions. The article analyzes the definition of social capital, its relationship with health, its limitations and potentialities from a perspective of community development and health promotion in Latin America. High-priority challenges are also identified as well as possible ways to better measure and to strengthen social capital. Particularly, it is discussed how and why social capital may be critical in a global health promotion strategy, where empowerment and community participation, interdisciplinary and intersectorial work would help to achieve Public Health aims and a sustainable positive change for the global development. Also, some potential limitations of the social capital concept in the context of health promotion in Latin America are identified

Promoting energy-saving behaviour : formal social groups as promising middle actors for municipal interventions

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)City governments worldwide are trying to motivate their citizens to reduce their energy use – a particular challenge as they try to reach individual households. A promising strategy to engage the public broadly entails collaborating with middle actors to multiply the effects of municipal interventions. Some of these middle actors are formal social groups (e.g. sports clubs and neighbourhood associations). We conducted an online experiment (N = 136) to determine whether such interventions were more effective when they are communicated through formal social groups than when communicated through city governments. Participants received letters containing advice for saving energy in the household. Willingness to participate was higher when the letters came from formal social groups than when they came from a city agency. Furthermore, actual members of formal social groups generally were more willing to participate. Our evidence suggests that formal social groups are promising middle actors for energy conservation campaigns and that city governments should engage more often with these groups to communicate with residents