- Nov 2023
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www.youtube.com www.youtube.com
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https://www.youtube.com/watch?v=9fP4zFQMXSw
The fun things usually happen at the messy edges. This description of zettelkasten is a perfect encapsulation of this, though it's not necessarily on the surface.
This is a well done encapsulation of what a zettelkasten. Watch it once, then practice for a bit. Knowing the process is dramatically different from practicing it. Too many people want perfection (perfection for them and from their perspective) and they're unlikely to arrive at it by seeing examples of others. The examples may help a bit, but after you've seen a few, you're not going to find a lot of insight without practicing it to see what works for you.
This could be compared with epigenetic factors with respect to health. The broad Rx may help, but epigenetic factors need to be taken into account.
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- Nov 2020
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www.quantamagazine.org www.quantamagazine.org
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serotonin has another function: It can act as one of those molecular Post-it notes. Specifically, it can bind to a type of histone known as H3, which controls the genes responsible for transforming human stem cells (the forerunner of all kinds of cells) into serotonin neurons. When serotonin binds to the histone, the DNA unwinds, turning on the genes that dictate the development of a stem cell into a serotonin neuron, while turning off other genes by keeping their DNA tightly wound. (So stem cells that never see serotonin turn into other types of cells, since the genetic program to transform them into neurons is not activated.)
Serotonin can bind to H3 Histone and cause stem cells to become serotonin neurons.
This research led the same team to wonder if Dopamine might act in a similar way.
The serotonin paper is here: https://pubmed.ncbi.nlm.nih.gov/30867594/
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To test that hypothesis, the researchers genetically modified H3 histones in rats by replacing the amino acid that dopamine attaches to with a different one it doesn’t react with. This stops dopaminylation from occurring. Withdrawal from cocaine is associated with changes in the readout of hundreds of genes involved in rewiring neural circuits and altering synaptic connections, but in the rats whose dopaminylation was prevented, these changes were suppressed. Moreover, neural impulse firing in VTA neurons was reduced, and they released less dopamine, showing that these genetic changes were indeed affecting the brain’s reward circuit operation. This might account for why people with substance use disorder crave drugs that boost dopamine levels in the brain during withdrawal. Finally, in subsequent tests, the genetically modified rats exhibited much less cocaine-seeking behavior
Rats were genetically modified to decrease dopaminylation (modifying M3 so dopamine couldn't attach). This correlated to the Ventral Tegmental Area firing less (less cocaine impulse) and released less dopamine. This showed that these changes to H3, and subsequently the dopaminylation, did impact brain's reward circuit operation.
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they showed that the same enzyme that attaches serotonin to H3 can also catalyze the attachment of dopamine to H3 — a process, I learned, called dopaminylation.
The same enzyme that helps serotonin bind to H3 can also help dopamine bind to H3.
Paper found here: https://pubmed.ncbi.nlm.nih.gov/32273471/
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if the magnetic tape remains tightly wound, you can’t read the information on the cassette. Epigenetics works by unspooling the tape, or not, to control which genetic instructions are carried out. In epigenetic inheritance, the DNA code is not altered, but access to it is.
An interesting way to describe epigenetics. It is like magnetic tape on a cassette, you have to unwind it to be able to read its content. Epigenetics, by analogy would be controlling the spooling of the DNA for accessibility.
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- May 2019
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www.drevafogelman.com www.drevafogelman.com
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The Third-Generation normalized the process of dialogue. Bar-On and his team developed a paradigm for how to work through the Holocaust through knowledge, understanding, emotions, attitude, and behavior. What they discovered is that for the Third-Generation, the Holocaust either has no relevance, which they call “under generalization” or “over generalization,” where everything is seen through the prism of the Holocaust. A more normalized reaction to a Shoah family background is the “partial relevance,” an “in-between” and more balanced perspective.
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The Third-Generation in America (or “3Gs,” as they are known) have only recently started to become a visible group, but not with the same intensity as the Second-Generation. Age-wise, they span the gamut from newborns to forty-year-olds. Among them, those in their twenties and thirties are grappling with identity formation, with establishing intimate relations, and with having children.
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From the psychological research the only significant finding is that grandchildren of survivors as a group, are higher achievers than their peers. In 2002 Ellisa Ganz found that Third-Generation individuals are twice as likely to choose an occupation in the helping professions. Ganz also found, however, that those 3Gs who are in therapy are in treatment for longer periods than a comparative group.
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Yoslow observed that the Third-Generation has a deep affection for humanity, which is a transformation of the post-Holocaust trauma. This process is the ability to transform the emotional effects of the Holocaust by letting go, and thus increases the quest for meaning in ones life and concern for social issues.
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Today, Third-Generation individuals whose professional lives have been shaped by their grandparent’s ordeals are found in the creative arts, in helping professions, human rights work and in Jewish studies and communal work. The Third-Generation members are no different from those in the Second-Generation, who gravitated towards the creative arts in order to remember the barbarity committed against the Jews living in German-occupied countries and , the Jewish life that was destroyed, and to raise consciousness about present-day racism, human-rights violations, and genocides.
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- Feb 2019
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www.cell.com www.cell.com
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Despite the fact that some environmentally induced changes are heritable, these effects are not stable [30Becker C. Weigel D. Epigenetic variation: origin and transgenerational inheritance.Curr. Opin. Plant Biol. 2012; 15: 562-567Crossref PubMed Scopus (62) Google Scholar]. Specifically, it has been shown that in large populations of Arabidopsis most ‘epi-mutations’ are labile — after only a few generations, these base-pair methylations revert to their original state. Hence, epigenetic modifications in plants are of very limited significance for evolutionary processes. Accordingly, neo-Lamarckian (including Lysenkoist) concepts have been experimentally refuted by these trans-generational epigenetic analyses [30Becker C. Weigel D. Epigenetic variation: origin and transgenerational inheritance.Curr. Opin. Plant Biol. 2012; 15: 562-567Crossref PubMed Scopus (62) Google Scholar].
Just one citation and that to an opinion article? Interesting...
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- Jun 2018
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www.nature.com www.nature.com
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Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs
Queuosine metabolite necessary for DNMT2-induced tRNA modification; salvaged from bacteria of microbiome
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- Jan 2018
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elifesciences.org elifesciences.org
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Dnmt3a is an epigenetic mediator of adipose insulin resistance
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- Dec 2017
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www.nature.com www.nature.com
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Statistical and integrative system-level analysis of DNA methylation data
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- Nov 2017
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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The background puzzle: how identical mutations in the same gene lead to different disease symptoms
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- Apr 2017
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while those that had been moved to 25 degrees had largely lost the methylation tags. Importantly, they still maintained this reduced histone methylation when moved back to the cooler temperature, suggesting that it is playing an important role in locking the memory into the transgenes.
Could it be that the genetic background (or importantly surrounding environment or cross talk among cells) in the first generation that were exposed to 25 C temp might have changed, and conditioned subsequent generations?
After 14 generations, secondary changes in the propoagated genetic makeup (including cross talk) could have reverted phenotype and reset histone marks to repress gene expression.
See if how often c.elegans mutate or show CN changes, i.e., background vs stress induced by temp changes?
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Worms are very short-lived, so perhaps they are transmitting memories of past conditions to help their descendants predict what their environment might be like in the future,
? as long as cost, e.g., energy consumption for propagating such beneficial features is not higher than needed for one's survival.
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