Elemental Ecocriticism - thinking with earth, air, water and fire [Book Review]

Review(s) of: Elemental Ecocriticism - thinking with earth, air, water and fire, Edited by Jeffrey Jerome Cohen and Lowell Duckert, Minnesota University Press, 2015.<div><br></div><div>PAN: Philosophy Activism Nature, No. 13, 2017: 117-118<br></div

The proteomic landscape of microglia in health and disease.

Microglia are the resident immune cells of the central nervous system (CNS) and as such play crucial roles in regulating brain homeostasis. Their presence in neurodegenerative diseases is known, with neurodegeneration-associated risk genes heavily expressed in microglia, highlighting their importance in contributing to disease pathogenesis. Transcriptomics studies have uncovered the heterogeneous landscape of microglia in health and disease, identifying important disease-associated signatures such as DAM, and insight into both the regional and temporal diversity of microglia phenotypes. Quantitative mass spectrometry methods are ever increasing in the field of neurodegeneration, utilised as ways to identify disease biomarkers and to gain deeper understanding of disease pathology. Proteins are the main mechanistic indicators of cellular function, yet discordance between transcript and proteomic findings has highlighted the need for in-depth proteomic phenotypic and functional analysis to fully understand disease kinetics at the cellular and molecular level. This review details the current progress of using proteomics to define microglia biology, the relationship between gene and protein expression in microglia, and the future of proteomics and emerging methods aiming to resolve heterogeneous cell landscapes

Additional file 1: Table S1. of Association of anthropometric measures with kidney disease progression and mortality: a retrospective cohort study of pre-dialysis chronic kidney disease patients referred to a specialist renal service

Association between baseline obesity parameters and the primary outcome in stage 3–4 chronic kidney disease stratified by gender. Comparison performed using Cox proportional hazards modelling to compare body mass index, waist circumference and conicity index with the composite outcome of doubling of serum creatinine, commencement of renal replacement therapy or all-cause mortality. Table S2. Association between baseline obesity parameters and all-cause mortality in stage 3–4 chronic kidney disease stratified by gender. Comparison performed using Cox proportional hazards modelling to compare body mass index, waist circumference and conicity index with all-cause mortality by gender. (DOCX 24 kb

Data_Sheet_1_Mitochondrial Translocator Protein (TSPO) Expression in the Brain After Whole Body Gamma Irradiation.PDF

The brain’s early response to low dose ionizing radiation, as may be encountered during diagnostic procedures and space exploration, is not yet fully characterized. In the brain parenchyma, the mitochondrial translocator protein (TSPO) is constitutively expressed at low levels by endothelial cells, and can therefore be used to assess the integrity of the brain’s vasculature. At the same time, the inducible expression of TSPO in activated microglia, the brain’s intrinsic immune cells, is a regularly observed early indicator of subtle or incipient brain pathology. Here, we explored the use of TSPO as a biomarker of brain tissue injury following whole body irradiation. Post-radiation responses were measured in C57BL/6 wild type (Tspo+/+) and TSPO knockout (Tspo–/–) mice 48 h after single whole body gamma irradiations with low doses 0, 0.01, and 0.1 Gy and a high dose of 2 Gy. Additionally, post-radiation responses of primary microglial cell cultures were measured at 1, 4, 24, and 48 h at an irradiation dose range of 0 Gy-2 Gy. TSPO mRNA and protein expression in the brain showed a decreased trend after 0.01 Gy relative to sham-irradiated controls, but remained unchanged after higher doses. Immunohistochemistry confirmed subtle decreases in TSPO expression after 0.01 Gy in vascular endothelial cells of the hippocampal region and in ependymal cells, with no detectable changes following higher doses. Cytokine concentrations in plasma after whole body irradiation showed differential changes in IL-6 and IL-10 with some variations between Tspo–/– and Tspo+/+ animals. The in vitro measurements of TSPO in primary microglial cell cultures showed a significant reduction 1 h after low dose irradiation (0.01 Gy). In summary, acute low and high doses of gamma irradiation up to 2 Gy reduced TSPO expression in the brain’s vascular compartment without de novo induction of TSPO expression in parenchymal microglia, while TSPO expression in directly irradiated, isolated, and thus highly activated microglia, too, was reduced after low dose irradiation. The potential link between TSPO, its role in mitochondrial energy metabolism and the selective radiation sensitivity, notably of cells with constitutive TSPO expression such as vascular endothelial cells, merits further exploration.</p

Deep proteomic analysis of microglia reveals fundamental biological differences between model systems.

Using high-resolution quantitative mass spectrometry, we present comprehensive human and mouse microglia proteomic datasets consisting of over 11,000 proteins across six microglia groups. Microglia share a core protein signature of over 5,600 proteins, yet fundamental differences are observed between species and culture conditions. Mouse microglia demonstrate proteome differences in inflammation- and Alzheimer's disease-associated proteins. We identify differences in the protein content of ex vivo and in vitro cells and significant proteome differences associated with protein synthesis, metabolism, microglia marker expression, and environmental sensors. Culturing microglia induces rapidly increased growth, protein content, and inflammatory protein expression. These changes are restored by engrafting in vitro cells into the brain, with xenografted human embryonic stem cell (hESC)-derived microglia closely resembling microglia from the human brain. These data provide an important resource for the field and highlight important considerations needed when using model systems to study human physiology and pathology of microglia