Degeneration of Neuronal Mitochondria in Parkinson’s Disease: Mitochondrial Turnover in Neuromuscular Junctions of Parkin Mutants.

The accumulation of dysfunctional or damaged mitochondria in neurons has been linked to the pathogenesis of many neurodegenerative diseases, including Parkinson’s disease. It has been proposed that the Parkinson’s-related proteins PINK1 and Parkin regulate mitochondrial quality control by selectively targeting depolarized mitochondria for autophagic degradation, a process known as mitophagy. The compartmentalization of mitochondrial turnover in neurons still remains unclear, but evidence suggests that mitochondria are locally degraded in the distal axon and perhaps in the neuromuscular junctions (NMJs). To study this, intact Drosophila nervous systems were analyzed in vivo by performing gentle dissections on third instar larvae to expose the ventral ganglia and segmental nerves with their NMJs. Both control larvae and parkin mutants (parkin25) were genetically modified to mark mitochondria via mitoGFP expression in their motor neurons, with park25 being additionally modified by deletion of the parkin gene. The physiological states of mitochondria were quantified through measurements of mitochondrial membrane potential, and the density of mitochondria in NMJs were analyzed through comparing αHRP and mitoGFP stain intensities in synaptic boutons. Unexpectedly, parkin25 mitochondria displayed normal readings in NMJs, indicating that mutant nerve terminals do not accumulate senescent mitochondria. In addition, reduced mitochondrial density was observed in synaptpark25ic boutons of parkin25 animals. These results argue against the hypothesis that loss of Parkin results in the accumulation of depolarized mitochondria, instead suggesting a reduction of organelle density in synaptic boutons as a result of Parkin deficiency. By elucidating the role of Parkin in the synapse of neurons, the pathogenic mechanism of Parkinson’s and other neurodegenerative diseases will be better understood

Analysis of Mitochondrial Turnover in Neuromuscular Junctions of Parkin Mutants

The accumulation of dysfunctional or damaged mitochondria in neurons has been linked to the pathogenesis of many neurodegenerative diseases, such as Parkinson’s disease. It has been proposed that proteins PINK1 and Parkin regulate mitochondrial quality control by selectively targeting depolarized mitochondria for autophagic degradation, a process known as mitophagy. Though previously analyzed in the cell bodies and axons of neurons, the role of the PINK1/Parkin pathway in the synapse is unclear, and it is not known whether mitochondrial turnover occurs in the neuromuscular junctions (NMJs). To study this, intact Drosophila nervous systems were analyzed in vivo by performing gentle dissections on third instar larvae to expose the ventral ganglia and segmental nerves with their NMJs. Both the control and parkin mutants were genetically modified to mark mitochondria via mito-GFP expression and autophagic vacuoles via RFP-atg8 expression in their motor neurons, with parkin mutants being additionally modified by the deletion of the Parkin gene. The physiological states of mitochondria were quantified through measurements of mitochondrial membrane potential, and the possible occurrence of mitophagy in the nerve terminals was tested through observations of GFP and RFP signal co-localization. Unexpectedly, mitochondria of parkin mutants displayed normal readings in NMJs, indicating that mitochondria from mutant nerve terminals exhibit normal physiological conditions. In addition, co-localization was not observed in thin axons adjacent to NMJs, suggesting that mitophagy is down-regulated in vivo. By elucidating the role of Parkin in the synapse of neurons, the manifestation of Parkinson’s and other neurodegenerative diseases will be better understood

Moving Towards a More Inclusive Reintegration: The Case of Demobilized Afro-Colombian Girl Child Soldiers

Colombia’s conflict started in 1964 and spanned over 50 years, until former President Juan Manuel Santos signed a peace deal that formally ended the conflict between the FARC-EP and the Colombian government. In total, different groups in the conflict recruited close to 17,000 children, a violation of their human rights under international human rights law. By conducting interviews with child protection experts and reviewing the ICBF’s policies on race and gender, this study seeks to understand the reintegration experiences of demobilized Afro-Colombian girls, how the ICBF takes into account race and gender in the design of their programs, and whether or not Colombia’s reintegration program adequately addresses the needs of demobilized Afro-Colombian girls. The findings of this study show that reintegration programs fail to adequately address their needs. Afro-Colombian girls have a distinct set of needs that reintegration programs must take into account when designing their programs, which include unique power relations within the armed groups, lack of basic services prior to their involvement with the armed groups as well as after their demobilization, and the violence still present in their communities upon their return. This study also found that the ICBF’s understanding of race and gender in the design of their programs is explicit and thorough, outlining the importance of incorporating race and gender. However, the findings show that the implementation of such mechanisms fall short of being effective and attainable. This study’s findings point to the need to be more inclusive in the design of the reintegration programs, and to take into account dangers present in the communities where Afro-Colombian girls will be returning to

War Weariness : Within The 21st Century & In The Global War On Terror

By the end of the 2010s, the United States of America had been in several military campaigns in the Global War on Terror. In the past, U.S. interventions often were swift and decisive campaigns and rarely lasted more than five years. This research paper’s main purpose is to publicize attitudes in relation to military and foreign policies within the 21st century. This was accomplished by analyzing two primary variables. This research paper looks into the correlation between military casualties in the War on Terror starting from 2004 to the present. The independent variables of this paper will be military fatalities with both the wars in Afghanistan and Iraq, while the dependent variable will be the support of U.S and its allies in the War on Terror with regard to if they are winning or not. Alongside this, a Fixed Effects model using years as a metric will be used to also analyze the results of this research. President Approval polling is also used as controlling measurement of framing within the U.S. political decision making elites. The results of this research paper indicate that there are significant correlations between approvals by the American public at varying points in time

Increase of reactive oxygen species contributes to growth inhibition by fluconazole in \u3cem\u3eCryptococcus neoformans\u3c/em\u3e

Background Cryptococcus neoformans, a basidiomycetous yeast, is a fungal pathogen that can colonize the lungs of humans causing pneumonia and fungal meningitis in severely immunocompromised individuals. Recent studies have implied that the antifungal drug fluconazole (FLC) can induce oxidative stress in C. neoformans by increasing the production of reactive oxygen species (ROS), as presence of the antioxidant ascorbic acid (AA) could reverse the inhibitory effects of FLC on C. neoformans. However, in Candida albicans, AA has been shown to stimulate the expression of genes essential for ergosterol biosynthesis. Hence, the contribution of ROS in FLC-mediated growth inhibition remains unclear. Results In order to determine whether counteracting ROS generated by FLC in C. neoformans can contribute to diminishing inhibitory effects of FLC, we tested three other antioxidants in addition to AA, namely, pyrrolidine dithiocarbamate (PDTC), retinoic acid (RA), and glutathione (GSH). Our data confirm that there is an increase in ROS in the presence of FLC in C. neoformans. Importantly, all four antioxidants reversed FLC-mediated growth inhibition of C. neoformans to various extents. We further verified the involvement of increased ROS in FLC-mediated growth inhibition by determining that ROS-scavenging proteins, metallothioneins (CMT1 and CMT2), contribute to growth recovery by PDTC and AA during treatment with FLC. Conclusion Our study suggests that ROS contributes to FLC-mediated growth inhibition and points to a complex nature of antioxidant-mediated growth rescue in the presence of FLC

Allergic airway inflammation induces upregulation of the expression of IL-23R by macrophages and not in CD3 + T cells and CD11c+F4/80- dendritic cells of the lung

Interleukin 23 and the interleukin 23 receptor (IL-23-IL23R) are described as the major enhancing factors for Interleukin 17 (IL-17) in allergic airway infammation. IL-17 is considered to induce neutrophilic infammation in the lung, which is often observed in severe, steroid-resistant asthma-phenotypes. For that reason, understanding of IL-23 and IL-17 axis is very important for future therapy strategies, targeting neutrophil pathway of bronchial asthma. This study aimed to investigate the distribution and expression of IL-23R under physiological and infammatory conditions. Therefore, a house dust mite (HDM) model of allergic airway infammation was performed by treating mice with HDM intranasally. Immunofuorescence staining with panel of antibodies was performed in lung tissues to examine the macrophage, dendritic cell, and T cell subpopulations. The allergic airway infammation was quantifed by histopathological analysis, ELISA measurements, and airway function. HDM-treated mice exhibited a signifcant allergic airway infammation including higher amounts of NE+ cells in lung parenchyma. We found only a small amount of IL-23R positives, out of total CD3+T cells, and no upregulation in HDMtreated animals. In contrast, the populations of F4/80+ macrophages and CD11c+F4/80− dendritic cells (DCs) with IL-23R expression were found to be higher. But HDM treatment leads to a signifcant increase of IL-23R+ macrophages, only. IL23R was expressed by every examined macrophage subpopulation, whereas only Mϕ1 and hybrids between Mϕ1 and Mϕ2 phenotype and not Mϕ2 were found to upregulate IL-23R. Co-localization of IL-23R and IL-17 was only observed in F4/80+ macrophages, suggesting F4/80+ macrophages express IL-23R along with IL-17 in lung tissue. The study revealed that macrophages involving the IL-23 and IL-17 pathway may provide a potential interesting therapeutic target in neutrophilic bronchial asthma

Central Africa Energy: Utilizing NASA Earth Observations to Explore Flared Gas as an Energy Source Alternative to Biomass in Central Africa

Much of Central Africa's economy is centered on oil production. Oil deposits lie below vast amounts of compressed natural gas. The latter is often flared off during oil extraction due to a lack of the infrastructure needed to utilize it for productive energy generation. Though gas flaring is discouraged by many due to its contributions to greenhouse emissions, it represents a waste process and is rarely tracked or recorded in this region. In contrast to this energy waste, roughly 80% of Africa's population lacks access to electricity and in turn uses biomass such as wood for heat and light. In addition to the dangers incurred from collecting and using biomass, the practice commonly leads to ecological change through the acquisition of wood from forests surrounding urban areas. The objective of this project was to gain insight on domestic energy usage in Central Africa, specifically Angola, Gabon, and the Republic of Congo. This was done through an analysis of deforestation, an estimation of gas flared, and a suitability study for the infrastructure needed to realize the natural gas resources. The energy from potential natural gas production was compared to the energy equivalent of the biomass being harvested. A site suitability study for natural gas pipeline routes from flare sites to populous locations was conducted to assess the feasibility of utilizing natural gas for domestic energy needs. Analyses and results were shared with project partners, as well as this project's open source approach to assessing the energy sector. Ultimately, Africa's growth demands energy for its people, and natural gas is already being produced by the flourishing petroleum industry in numerous African countries. By utilizing this gas, Africa could reduce flaring, recuperate the financial and environmental loss that flaring accounts for, and unlock a plentiful domestic energy source for its people. II. Introduction Background Africa is home to numerous burgeoning economies; a significant number rely on oil production as their primary source of revenue. Relative to its size and population density, the continent has a wealth of natural resources, including oil and natural gas deposits. The exploration of these resources is not a new endeavor, but rather one that spans decades, up to a century in some places. Their resources, if realized, could provide a great means of economic and social mobility for the people of Africa. Currently, Africa represents about 12 % of the energy market, yet at the same time, consumes only 3 % of the world's energy (Kasekende 2009). The highe