Cultists go mad all the time, it’s a common occurrence, but this particular cultist lost her mind a lot quicker than they usually do. Staying too long in the shadows will do that to a person, and this cultist had let the shadows into her heart. The cultist had sensed Him, had heard His whispers, and the cultist was now ready to act on what she had heard. Dark words, chaos and madness, the cultist was ready to slaughter all, and not in the name of her village, but in His name; The Lord of Shadows.
The Lord of Shadows had been watching the hearthlands for some time, amused by the state of the world. The village of Ry’leh had become very interesting to Him, as they were quite happy to run their pretty mouths, trying to distort reality123. The Lord of Shadows knew their game and realized the villagers of Ry’eleh were new to it, so He decided to teach them about the dark arts. Now all He needed was a suitable target, someone to fall prey to His corrupting influence. The Lord of Shadows was in luck, a perfect target had dwelled in just the places where He wielded most power, His plans were ready to be set in motion.
On the eve of the Lord of Shadows flight, He sent a message of possible forgiveness. Not everyone can hear the Lord of Shadows voice, and those fortunate enough rarely heed it. The village of Ryl’eh has only themselves to blame for not accepting the Lord of Shadows inside their heart and body. The Lord of Shadows felt stronger than ever, as the day of reckoning approached. His shadowy domain was as vast as ever, since the Oddgod’s mighty penis stretched into the sky, towering over all of the hearthlands and creating a massive shadow. The fruit was ripe for picking, the lesson was ready to be taught.
Upon arriving, the Lord of Shadows immediately smelled the filth of pagans and scum, their failure to accept the Lord of Shadows into their hearts agitating and empowering him. The Lord of Shadows thrives off of those who oppose him. All he needs is a soul that truly understands the world to let him in. His mere approach began to tear the village asunder. Men and women, scared for their lives, rushed into their houses while their piles and chests tumbled over. The Lord of Shadows would not let any filth escape. The unfaithful were individually slain as his long reaching hand snuck their fingers into each home. All attempts to resist were fruitless.
The most prevalent neurodegenerative diseases share common pathophysiological mechanisms, such as mitochondrial dysfunction, oxidative stress, and cell death, yet the particular neuronal population involved dictates the symptomatic presentation of disease. Parkinson's disease and Huntington's disease, but also familial amyotrophic lateral sclerosis, Alzheimer's disease and some types of epilepsies are characterized by severe neuronal losses. Strikingly, neuronal losses show high regional specificity and frequently follow distinct patterns: Parkinson's disease affects mainly dopaminergic neurons in the substantia nigra (Hirsch et al., 1988), while Huntington's disease is associated with neuronal loss in the motor cortex and striatum (Lange et al., 1976). One research focus in our quest to understand this phenomenon is mitochondrial dysfunction and oxidative stress. Mitochondrial dysfunction may be restricted to affected regions and heterogeneity of mitochondrial parameters has been described in different brain areas (for review see Dubinsky, 2009). However, a major unanswered question is if region-specific differences in basal mitochondrial function predispose select neuronal populations to pathological stimuli, or if mitochondrial energetics are similar throughout, but the neurons are selectively vulnerable to events downstream of mitochondrial dysfunction.
Oxidative phosphorylation (OXPHOS) is a major player in energy transformation, where the subsystems of the electron transfer system (ETS) generate the transmembrane protonmotive force and the phosphorylation system utilizes the protonmotive force. The main ETS protein complexes are located in the inner mitochondrial membrane and pump protons to drive the phosphorylation of ADP to ATP. Dysfunction of a single protein or entire complex of the OXPHOS-machinery due to genetic mutations cannot explain per se the regional specificity of neurodegenerative diseases. However, the expression of mitochondrial proteins is regulated epigenetically, therefore regional or even cellular specificity of the contribution of distinct complexes may be regulated by cell specific gene expression mechanisms.
Specifically Complexes I, II and IV (CI, CII and CIV) in distinct brain regions are presently discussed as being affected in a number of classical neurodegenerative diseases, such as Parkinson's disease (Schapira et al., 1989), Huntington's disease (Gu et al., 1996) and Alzheimer's disease (Crouch et al., 2005) as well as in several types of epilepsies (for reviews see (Baron et al., 2007 and Waldbaum and Patel, 2010a), such as temporal lobe epilepsy (Kunz et al., 2000). Accordingly, the contribution of the distinct complexes to mitochondrial function needs to be studied in a regionally-specific context in order to reveal the causal relationship between mitochondrial vulnerability and pathological processes. Isolated mitochondria are often used to study mitochondrial parameters in cells or tissues (Perry et al., 2013). By contrast studying distinct mitochondrial functions in brain microsamples requires a method with low preparative loss and close to physiological tissue environments. Recently, Herbst and Holloway (Herbst and Holloway, 2015) compared the respiration of permeabilized brain tissues and mitochondria isolated from cortex. They conclude that permeabilized brain tissue offers several advantages, such as minimization of time and tissue required for measurements carried out under more physiological mitochondrial conditions.
The aim of the present study was to establish a further developed method, which would enable detailed analysis of mitochondrial functional within specific regions of the brain. Considering the ongoing discussions on mitochondrial complexes involved in neurological diseases, the main focus was put on integrated CI-, and CII-linked mitochondrial pathways under coupled and noncoupled conditions, and the single enzymatic step of cytochrome c oxidase (CIV; Gnaiger, 2014). A complex substrate-uncoupler-inhibitor-titration (SUIT) protocol was applied for mitochondrial phenotyping (comprehensive OXPHOS analysis) in a single incubation of small tissue samples of 2 mg fresh weight. The method was sufficiently sensitive to reveal functional differences between distinct brain areas in control animals, and between the ipsi- and contralateral dorsal hippocampi in a mouse model of temporal lobe epilepsy. The omission of detergents in the tissue preparation and our SUIT-protocol allow evaluation of several subsequentially targeted substrate and coupling states without compromising the stability of respiration. Reference states addressed within a SUIT protocol can be selected as internal functional mitochondrial markers, which have been validated in this study.
CRISPRs (clustered regularly interspaced short palindromic repeats) are segments of prokaryotic DNA containing short repetitions of base sequences. Each repetition is followed by short segments of "spacer DNA" from previous exposures to a bacterial virus or plasmid.[2] It is pronounced "crisper".[3] The CRISPR/Cas system is a prokaryotic immune system that confers resistance to foreign genetic elements such as plasmids and phages,[4][5] and provides a form of acquired immunity. CRISPR spacers recognize and cut these exogenous genetic elements in a manner analogous to RNAi in eukaryotic organisms.[2] CRISPRs are found in approximately 40% of sequenced bacteria genomes and 90% of sequenced archaea.[6][note 1] The CRISPR/Cas system has been used for gene editing (adding, disrupting or changing the sequence of specific genes) and gene regulation in species throughout the tree of life.[7] By delivering the Cas9 protein and appropriate guide RNAs into a cell, the organism's genome can be relatively cheaply cut at any desired location.[8][9][10] CRISPR has a number of potential applications including treating genetic diseases, fighting infections, and increasing food crop yields, but the application of this method is accompanied by ethical concerns.[11]
As Rly’eh succumbs to and learns to love the watery embrace of the Lord of Shadows, one wonders: Who will the Lord of Shadows purify next?
The sea of ignorance is vast, and the lesson the Lord of Shadows ended up teaching was this: If you have an un’rlyheable grasp of the dark arts, keep your head above water by not shitting yourself, shitters.
the proliferation of automation is the rot of this game, with the next worst thing being the filth that plays it (you, probably.)
W7 - Hermit W8 - Co-LS of R'lyeh, Owner of the Hermitarium Knowledge Group W9 - LS of Niflheim W11 - Hermitage (named Niflheim) W12 - Hermit -> some rando ass village i forgot the name of that i joined W10,13-15 - N/A
Endora wrote:Bob Dole tried to warn you guys threads ago that JoCo sold you out. You didn't learn from your mistake and you paid for it.
Bob Dole is a kind soul, that didn't want your village to fall due to the nasty coles. He tried to warn you of his evil ways, but you did not listen, and let Doles into your midst.
The guy with the bow and a fox hat was MVP, KO'd like 3 of us. Looking forward to the combat changes patch. Also, thanks to Robben, Bob, et. al for gathering a zerg on the very limited information we provided (gank opportunity)
The low life has lost its appeal And I'm tired of walking these streets To a room with its cupboards bare
