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John goodier supermind8/28/2023 ![]() ![]() Using immunocytochemistry, RNA analyses, coimmunoprecipitation, and a functional assay for L1 ORF2 reverse transcriptase activity, we will examine brain tissue and derived iPS cell lines, mainly from ALS patients but also including AD samples, and compare these with age-matched controls to ascertain if L1 RNA and protein expression is elevated in the disease state. However, recent investigations show that these defenses are occasionally relaxed, leading to increased retrotransposon activity in certain somatic cell types, including stem cells, some cancers, and notably neuronal cells in the human brain. The cell in turn has evolved defenses against unrestricted retrotransposition, including DNA methylation, chromatin remodeling, nucleic acid editing, and RNA interference. L1 retrotransposition has also been responsible for the insertion of over a million non- autonomous Alu retroposons and thousands of processed pseudogenes. The Human Genome Project estimated that over 500,000 L1 copies occupy 17% of human DNA, although it is believed that only about 100 of these remain potentially active in any individual. LINE1 retrotransposons are non-viral mobile DNA elements that duplicate themselves by a """"""""copy and paste"""""""" mechanism using an RNA intermediate. Furthermore, a corresponding increase in L1 ORF2 protein could account for increased levels of reverse transcriptase activity that have been detected in sera of ALS patients. ![]() We predict that the consequent increase in cellular levels of the L1-encoded ORF1p RNA-binding protein could increase its binding to proteins of significance for ALS or AD and promote their sequestration in stress granules and other cytoplasmic aggregates. We propose a novel hypothesis: rather than mutations at single gene locus, increased expression of ubiquitous LINE1 (L1) retrotransposons in the brains of ALS or AD patients, perhaps from many locations in the genome, contribute to the disease pathology. However, one common feature of many neurodegenerative diseases is protein aggregation, and it is widely thought that revealing the processes of cytoplasmic aggregate formation is key to better understanding the disease. A number of genes have been found, each explaining a minor percentage of familial cases and contributing little to our understanding of the pathogenesis of sporadic cases. Much effort has been expended identifying susceptibility genes for amyotrophic lateral sclerosis (ALS) and Alzheimer's (AD) disease. I don't really know if it's fair to write a critical review just because I expected something completely different.Understanding the causes of neurodegenerative diseases with the aim of developing effective treatments is a significant medical challenge. Accurate scientific descriptions of dying stars and the universe evolution are beautiful and captivating, and the brief stories about scientists in pursuit of extraterrestrial life ar I don't really know if it's fair to write a critical review just because I expected something completely different. And to some extent you can feel it in his book.īeing a John's subscriber on YouTube I decided to give it a go because unlike most sci-fi writers he seems to be really into hard science and cosmology. Accurate scientific descriptions of dying stars and the universe evolution are beautiful and captivating, and the brief stories about scientists in pursuit of extraterrestrial life are also very unusual and exactly what I was looking for. ![]() ![]() Too bad it all takes around 5% of the book. The rest fall so much short of what I expected! The book takes itself very seriously, and has this vibe of sad melancholy raising very 'deep' questions on pretty much every page, revolving around religion, technology augmentation, in a clichéd dystopian society that, as genre demands, depicted in a way that you don't really want to live in, and (oh my goodness please NOOO) human feelings and love, that the AI tries to understand in a series of cheesy dialog. "Would you kill in the name of Love?" the incredibly powerful AI asks a human at some point, as if with it's power it couldn't analyze the entirety of the human history and make a perfect model of human behavior and accurately predict what exactly people can do in the name of love, as well as other feelings such as greed, envy, lust, hunger for power etc. "Love is the ultimate manifestation of the Universe" - a human would answer. These 'deep' dilemmas are spoon-fed to the reader. I mean, a good story shouldn't tell the reader how to feel and what to ask, it should *make* them feel it and ask it themselves via the means of narration.īut the biggest disappointment for me personally was the lack of hard science, and solid logic behind the story. ![]()
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