Furthermore, when pericytes were exposed the ubiquitin proteasome inhibitor-MG132 and α-syn aggregates, there was profound cytotoxicity through the production of reactive oxygen species resulting in apoptosis. Although α-syn did not induce an inflammatory response, pericytes efficiently take up and degrade α-syn through the lysosomal pathway but not the ubiquitin–proteasome system. We found that the two α-syn aggregates are devoid of inflammatory and cytotoxic actions on human brain derived pericytes and microglia. Fixed flow cytometry was used to investigate the uptake and subsequent degradation of α-syn in pericytes. Inflammatory responses were assessed using immunocytochemistry, cytometric bead arrays and proteome profiler cytokine array kits. In this study, primary human brain pericytes and microglia were exposed to two different α-synuclein aggregates. Pericytes and microglia, two non-neuronal cells contain α-syn in the human brain, however, their role in disease processes is poorly understood. Pericytes, found surrounding the capillaries in the brain are important for maintaining the blood–brain barrier, controlling blood flow and mediating inflammation. If you’re clever, you might even be able to run a base off colonist farts.Įxplore Diverse, Procedurally Generated New Worlds:Summon new worlds with a push of a button.Parkinson’s disease (PD) is characterised by the progressive loss of midbrain dopaminergic neurons and the presence of aggregated α-synuclein (α-syn). Recycle waste into precious fuel, process unbreathable gas into air or harness the natural bodily processes of wild creatures for food. Waste Nothing through Extreme Recycling:Make use of every last resource for a base that truly exemplifies efficiency. Monitor carbon dioxide accumulation and oversee oxygen generation processes to mold your colony into a veritable deep-space oasis. Manage power runoff, circuit overloads and meltdowns to keep your colony running smoothly.Īlways Keep Yourself Breathing:Enter the Oxygen Overlay and watch air moving through your base in real time. Take Charge with Power Grid Simulations:Choose from a multitude of power sources including coal, hydrogen, natural gas or just plain old elbow grease. Plan well and be rewarded as your colony transforms into an imperishable, well-oiled machine. Keep tabs on ambient environmental temperatures and your colony's heat production to maintain a nice, cozy atmosphere for your colonists.Įnhance Efficiency through Complex Gas and Liquid Simulations:Create interlocking pipe systems to swiftly deliver fuel and liquid to critical areas of your base. Whatever the cost.Īvoid Boiling with Thermodynamics:Temperature control is a constant concern in space too cold and you'll freeze, too hot and you'll fry. Duplicants each have different and potentially destructive ways of reacting to stress, so be sure to always keep them happy.
It’s Mind Over Matter with Stress Simulations:Keep the psychological impact of survival at bay with fun leisure activities, great accommodations and even better food for your colony. Resources will begin depleting with your first breath, however, so be sure to dig fast if you want to live. Just make sure you don't forget to breathe.īuild Extensive Bases and Discover What it Takes to Survive:Everything in your space colony is under your control, from excavation and resource allocation right down to plumbing and power systems. Guide colonists through the perils of subterranean asteroid living and watch as their population grows until they're not simply surviving, but thriving. In the space-colony simulation game Oxygen Not Included you’ll find that scarcities of oxygen, warmth and sustenance are constant threats to your colony's survival.
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