• Moe Factz with Adam Curry for April 6th 2020, Episode number 32

• Nocebo

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  • Adam and Moe discuss the power of thought and suggestion in this journey through the world of mind control and media

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  • Inside Farrakhan and the Nation of Islam's Strange Ties to Scientology
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    • Mon, 06 Apr 2020 22:14
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    • You probably know about the Church of Scientology's courting of Hollywood celebrities, from Tom Cruise to John Travolta to the woman who's the voice of Bart Simpson, and perhaps you've caught wind of its cozy relationship with the Los Angeles Police Department.
    • But few are aware of its close partnership with the Nation of Islam, led by Minister Louis Farrakhan.
    • The approximately 20,000-strong black political and religious movement was formed in 1930 to improve the lives of black Americans, but in recent years has come under fire for its anti-gay, anti-white, and anti-Semitic views. Farrakhan, a vocal anti-Semite, found himself back in the news recently when he was cited as one of the reasons for the implosion of the Women's March, with some leaders of the movement accused of supporting Farrakhan and parroting his anti-Semitic talking points.
    • The alliance between the Nation of Islam, a black organization, and Scientology, an almost entirely white one, was hatched in the mid-Aughts, when the late Isaac Hayes, one of the only famous black Scientologists, approached Scientology leader David Miscavige and asked why the ''religion'' wasn't doing more to court black Americans. So Miscavige reached out to the Nation of Islam, and by 2010, they began promoting the ''benefits'' of Dianetics, the core set of ideas preached by Scientology founder L. Ron Hubbard.
    • During a sermon in Chicago on July 1, 2012, Farrakhan proclaimed to his acolytes, ''I found the tool that I know can help us. And I thank God for Mr. L. Ron Hubbard. And I thank God for his research and teaching.''
    • The latest episode of Leah Remini: Scientology and the Aftermath, A&E's Emmy-winning docuseries, examines the ties between the Church of Scientology and the Nation of Islam. And who better to guide us through it than Remini, who says she was tasked with strengthening the partnership.
    • ''I was approached by Scientology to bridge the gap between Scientology and the black community. And I wanted to do that. I had no idea what the Nation of Islam was,'' Remini says. ''I was a Scientologist and I wasn't questioning what my church was asking me to do.'' (The church, for its part, sent a letter less than 24 hours prior to the episode's airing, claiming that it ''supports religious freedom'' and comparing Remini's show to Nazism.)
    • The first guest joining Remini and her co-host Mike Rinder, a former Scientology executive, was Ishmael Bey, a decade-long member of the Nation of Islam who quit over its relationship with Scientology'--indeed a curious one, given that L. Ron Hubbard has said ''there was no Christ,'' and did not believe in the existence of Allah.
    • ''We started to see that buildings were being made, that the Nation of Islam were having secret meetings with Scientology that the public had no idea about. It started going in a different direction than the core tenets of what Islam actually represented,'' Bey said.
    • According to Bey, the Nation of Islam began administering Self-Improvement Courses, or the introductory courses that people take to enter into Scientology that are disguised as innocuous self-help courses.
    • ''The breaking point for me was when it started going in that direction with the self-improvement study guides. It started feeling very cult-like to me,'' Bey claims.
    • ''They now call him 'The Honorable LRH,' they now meet in the Scientology buildings, they now are being bestowed with the Scientology awards, and within the Nation of Islam, it's now a celebrated thing that the first female went 'clear' recently, and in 2015 the first male went 'clear,''' Bey added, referring to one of the most advanced statuses (or states of mind, as they put it) in Scientology.
    • Scientology has a policy that any of its members who recruit someone into the religion get to receive 10 percent of whatever their recruit pays into it, which can equal tens of thousands of dollars over a period of time. And there have been whispers and reports over the years that Farrakhan has received similar kickbacks from Scientology for spreading their gospel.
    • But that's not all. Remini contends that, ''They were coming to people like me, and they were saying, 'Hey, we want you guys to sponsor Nation of Islam members to come in and do these [Scientology] seminars.''
    • She claims that one of the Nation of Islam members whose Scientology courses she sponsored was Tony Muhammad, the West Coast regional minister of the Nation of Islam who was also identified by Bey as introducing many Nation of Islam-ers to Scientology. Muhammad is plastered all over the Scientology website, and he was recently bestowed with the IAS Freedom Medal, Scientology's biggest award.
    • ''I have become a better Muslim as a result of my relationship to the Church of Scientology,'' Muhammad says in a Scientology promotional video. ''The world should be grateful that in our lifetime, along came a being known as Mr. L. Ron Hubbard'... We say that when a man comes along like that, his name should be mentioned right along with the names of the saints.''
    • The next guest on the program was Hector Falu-Muhammad, a 26-year member of the Nation of Islam who worked closely with its senior officials.
    • Falu-Muhammad said that after he expressed his dissent against Dianetics to officials, he found himself ''singled out,'' and was subsequently accused by fellow Nation of Islam members of everything from stealing to committing indecent sex acts on his wife. This policy of attacking critics or ''enemies,'' Remini and Rinder note, is straight out of the Scientology handbook, and Falu-Muhammad claims that it was instituted after the two movements became bedfellows.
    • ''There's been a command that came from a member of Minister Farrakhan's personal staff. He said, if anyone is critical of Minister Farrakhan, to 'attack him like a hornet's nest,''' Falu-Muhammad says.
    • ''You're told, 'Hey, you better stop talking about Scientology, you're gonna get put out the mosque.' It's almost like Dianetics is the law now of the Nation of Islam,'' adds Bey.
    • ''The one thing that infuriates me the most is you find pictures of children in the Nation holding Dianetics books,'' Falu-Muhammad offers. ''We have children that are in the Nation. I don't want my children studying Dianetics, or studying Scientology.'' (The Nation of Islam did not respond to requests for comment.)
    • In addition to its courtship of the Nation of Islam and some local black churches, the Church of Scientology has recently erected giant centers in Atlanta, Harlem, Inglewood, and other predominately black communities'--although as Tiponi Grey, who worked in the Inglewood organization of Scientology, says, she only witnessed ''at most 10 people'' inside the building on a given day.
    • And Farrakhan addressed Remini and her Scientology whistle-blowing in a recent speech to his congregants.
    • ''I know that this is the time that they're making an all-out move to destroy Scientology,'' Farrakhan said. ''But what I'd ask Mrs. Renmie [sic], or whatever her name is, she's going in hard. She's hurt by something. I know a lot of Muslims that's hurt. Hurt because they came in looking for something, but didn't necessarily find what they were lookin' for, and walked away. And when you walked away, where did you go, what did you do, how did you gain, what did you lose?''
    • ''Nobody's trying to take Scientology down for reasons that are unwarranted,'' Remini fired back. ''And once you're in Scientology for a good 35, 45 years, maybe then ask these kinds of questions. And you should ask these types of questions to the families who have been destroyed.''
  • Epigenetics - Wikipedia
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    • Mon, 06 Apr 2020 22:12
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    • study of heritable DNA and histone modifications that affect the expression of a gene without a change in its nucleotide sequence.
    • In biology, epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence.[1] The Greek prefix epi- (ἐÏι- "over, outside of, around") in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic basis for inheritance.[2] Epigenetics most often involves changes that affect gene activity and expression, but the term can also be used to describe any heritable phenotypic change. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors, or be part of normal development. The standard definition of epigenetics requires these alterations to be heritable[3][4] in the progeny of either cells or organisms.
    • The term also refers to the changes themselves: functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and histone modification, each of which alters how genes are expressed without altering the underlying DNA sequence. Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA. These epigenetic changes may last through cell divisions for the duration of the cell's life, and may also last for multiple generations, even though they do not involve changes in the underlying DNA sequence of the organism;[5] instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently.[6]
    • One example of an epigenetic change in eukaryotic biology is the process of cellular differentiation. During morphogenesis, totipotent stem cells become the various pluripotent cell lines of the embryo, which in turn become fully differentiated cells. In other words, as a single fertilized egg cell '' the zygote '' continues to divide, the resulting daughter cells change into all the different cell types in an organism, including neurons, muscle cells, epithelium, endothelium of blood vessels, etc., by activating some genes while inhibiting the expression of others.[7]
    • Historically, some phenomena not necessarily heritable have also been described as epigenetic. For example, the term "epigenetic" has been used to describe any modification of chromosomal regions, especially histone modifications, whether or not these changes are heritable or associated with a phenotype. The consensus definition now requires a trait to be heritable for it to be considered epigenetic.[4]
    • Definitions [ edit ] The term epigenetics in its contemporary usage emerged in the 1990s, but for some years has been used with somewhat variable meanings.[8] A consensus definition of the concept of epigenetic trait as a "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence" was formulated at a Cold Spring Harbor meeting in 2008,[4] although alternate definitions that include non-heritable traits are still being used.[9]
    • The term epigenesis has a generic meaning of "extra growth", and has been used in English since the 17th century.[10]
    • Waddington's canalisation, 1940s [ edit ] From the generic meaning, and the associated adjective epigenetic, British embryologist C. H. Waddington coined the term epigenetics in 1942 as pertaining to epigenesis, in parallel to Valentin Haecker's 'phenogenetics' (Ph¤nogenetik).[11] Epigenesis in the context of the biology of that period referred to the differentiation of cells from their initial totipotent state during embryonic development.[12]
    • When Waddington coined the term, the physical nature of genes and their role in heredity was not known. He used it instead as a conceptual model of how genetic components might interact with their surroundings to produce a phenotype; he used the phrase "epigenetic landscape" as a metaphor for biological development. Waddington held that cell fates were established during development in a process he called canalisation much as a marble rolls down to the point of lowest local elevation.[13] Waddington suggested visualising increasing irreversibility of cell type differentiation as ridges rising between the valleys where the marbles (analogous to cells) are travelling.[14]
    • In recent times, Waddington's notion of the epigenetic landscape has been rigorously formalized in the context of the systems dynamics state approach to the study of cell-fate.[15][16] Cell-fate determination is predicted to exhibit certain dynamics, such as attractor-convergence (the attractor can be an equilibrium point, limit cycle or strange attractor) or oscillatory.[16]
    • Contemporary [ edit ] Robin Holliday defined epigenetics as "the study of the mechanisms of temporal and spatial control of gene activity during the development of complex organisms".[17] Thus, in its broadest sense, epigenetic can be used to describe anything other than DNA sequence that influences the development of an organism.
    • More recent usage of the word in biology follows stricter definitions. It is, as defined by Arthur Riggs and colleagues, "the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence".[18]
    • The term has also been used, however, to describe processes which have not been demonstrated to be heritable, such as some forms of histone modification; there are therefore attempts to redefine "epigenetics" in broader terms that would avoid the constraints of requiring heritability. For example, Adrian Bird defined epigenetics as "the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states".[5] This definition would be inclusive of transient modifications associated with DNA repair or cell-cycle phases as well as stable changes maintained across multiple cell generations, but exclude others such as templating of membrane architecture and prions unless they impinge on chromosome function. Such redefinitions however are not universally accepted and are still subject to debate.[3] The NIH "Roadmap Epigenomics Project", ongoing as of 2016, uses the following definition: "For purposes of this program, epigenetics refers to both heritable changes in gene activity and expression (in the progeny of cells or of individuals) and also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable."[9] In 2008, a consensus definition of the epigenetic trait, a "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence", was made at a Cold Spring Harbor meeting.[4]
    • The similarity of the word to "genetics" has generated many parallel usages. The "epigenome" is a parallel to the word "genome", referring to the overall epigenetic state of a cell, and epigenomics refers to global analyses of epigenetic changes across the entire genome.[9] The phrase "genetic code" has also been adapted '' the "epigenetic code" has been used to describe the set of epigenetic features that create different phenotypes in different cells from the same underlying DNA sequence. Taken to its extreme, the "epigenetic code" could represent the total state of the cell, with the position of each molecule accounted for in an epigenomic map, a diagrammatic representation of the gene expression, DNA methylation and histone modification status of a particular genomic region. More typically, the term is used in reference to systematic efforts to measure specific, relevant forms of epigenetic information such as the histone code or DNA methylation patterns.[citation needed ]
    • Developmental psychology [ edit ] In a sense somewhat unrelated to its use in biological disciplines, the term "epigenetic" has also been used in developmental psychology to describe psychological development as the result of an ongoing, bi-directional interchange between heredity and the environment.[19] Interactive ideas of development have been discussed in various forms and under various names throughout the 19th and 20th centuries. An early version was proposed, among the founding statements in embryology, by Karl Ernst von Baer and popularized by Ernst Haeckel. A radical epigenetic view (physiological epigenesis) was developed by Paul Wintrebert. Another variation, probabilistic epigenesis, was presented by Gilbert Gottlieb in 2003.[20] This view encompasses all of the possible developing factors on an organism and how they not only influence the organism and each other but how the organism also influences its own development.
    • The developmental psychologist Erik Erikson wrote of an epigenetic principle in his 1968 book Identity: Youth and Crisis, encompassing the notion that we develop through an unfolding of our personality in predetermined stages, and that our environment and surrounding culture influence how we progress through these stages. This biological unfolding in relation to our socio-cultural settings is done in stages of psychosocial development, where "progress through each stage is in part determined by our success, or lack of success, in all the previous stages."[21][22][23]
    • Although empirical studies have yielded discrepant results, epigenetic modifications are thought to be a biological mechanism for transgenerational trauma.
    • Molecular basis [ edit ] Epigenetic changes modify the activation of certain genes, but not the genetic code sequence of DNA. The microstructure (not code) of DNA itself or the associated chromatin proteins may be modified, causing activation or silencing. This mechanism enables differentiated cells in a multicellular organism to express only the genes that are necessary for their own activity. Epigenetic changes are preserved when cells divide. Most epigenetic changes only occur within the course of one individual organism's lifetime; however, these epigenetic changes can be transmitted to the organism's offspring through a process called transgenerational epigenetic inheritance. Moreover, if gene inactivation occurs in a sperm or egg cell that results in fertilization, this epigenetic modification may also be transferred to the next generation.[24]
    • Specific epigenetic processes include paramutation, bookmarking, imprinting, gene silencing, X chromosome inactivation, position effect, DNA methylation reprogramming, transvection, maternal effects, the progress of carcinogenesis, many effects of teratogens, regulation of histone modifications and heterochromatin, and technical limitations affecting parthenogenesis and cloning.
    • DNA damage [ edit ] DNA damage can also cause epigenetic changes.[25][26][27] DNA damage is very frequent, occurring on average about 60,000 times a day per cell of the human body (see DNA damage (naturally occurring)). These damages are largely repaired, but at the site of a DNA repair, epigenetic changes can remain.[28] In particular, a double strand break in DNA can initiate unprogrammed epigenetic gene silencing both by causing DNA methylation as well as by promoting silencing types of histone modifications (chromatin remodeling - see next section).[29] In addition, the enzyme Parp1 (poly(ADP)-ribose polymerase) and its product poly(ADP)-ribose (PAR) accumulate at sites of DNA damage as part of a repair process.[30] This accumulation, in turn, directs recruitment and activation of the chromatin remodeling protein ALC1 that can cause nucleosome remodeling.[31] Nucleosome remodeling has been found to cause, for instance, epigenetic silencing of DNA repair gene MLH1.[18][32] DNA damaging chemicals, such as benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene, cause considerable hypomethylation of DNA, some through the activation of oxidative stress pathways.[33]
    • Foods are known to alter the epigenetics of rats on different diets.[34] Some food components epigenetically increase the levels of DNA repair enzymes such as MGMT and MLH1[35] and p53.[36][37] Other food components can reduce DNA damage, such as soy isoflavones. In one study, markers for oxidative stress, such as modified nucleotides that can result from DNA damage, were decreased by a 3-week diet supplemented with soy.[38] A decrease in oxidative DNA damage was also observed 2 h after consumption of anthocyanin-rich bilberry (Vaccinium myrtillius L.) pomace extract.[39]
    • Techniques used to study epigenetics [ edit ] Epigenetic research uses a wide range of molecular biological techniques to further understanding of epigenetic phenomena, including chromatin immunoprecipitation (together with its large-scale variants ChIP-on-chip and ChIP-Seq), fluorescent in situ hybridization, methylation-sensitive restriction enzymes, DNA adenine methyltransferase identification (DamID) and bisulfite sequencing.[40] Furthermore, the use of bioinformatics methods has a role in computational epigenetics.[40]
    • Mechanisms [ edit ] Several types of epigenetic inheritance systems may play a role in what has become known as cell memory,[41] note however that not all of these are universally accepted to be examples of epigenetics.
    • Covalent modifications [ edit ] Covalent modifications of either DNA (e.g. cytosine methylation and hydroxymethylation) or of histone proteins (e.g. lysine acetylation, lysine and arginine methylation, serine and threonine phosphorylation, and lysine ubiquitination and sumoylation) play central roles in many types of epigenetic inheritance. Therefore, the word "epigenetics" is sometimes used as a synonym for these processes. However, this can be misleading. Chromatin remodeling is not always inherited, and not all epigenetic inheritance involves chromatin remodeling.[42] In 2019, a further lysine modification appeared in the scientific literature linking epigenetics modification to cell metabolism, i.e. Lactylation[43]
    • DNA associates with histone proteins to form chromatin.
    • Because the phenotype of a cell or individual is affected by which of its genes are transcribed, heritable transcription states can give rise to epigenetic effects. There are several layers of regulation of gene expression. One way that genes are regulated is through the remodeling of chromatin. Chromatin is the complex of DNA and the histone proteins with which it associates. If the way that DNA is wrapped around the histones changes, gene expression can change as well. Chromatin remodeling is accomplished through two main mechanisms:
    • The first way is post translational modification of the amino acids that make up histone proteins. Histone proteins are made up of long chains of amino acids. If the amino acids that are in the chain are changed, the shape of the histone might be modified. DNA is not completely unwound during replication. It is possible, then, that the modified histones may be carried into each new copy of the DNA. Once there, these histones may act as templates, initiating the surrounding new histones to be shaped in the new manner. By altering the shape of the histones around them, these modified histones would ensure that a lineage-specific transcription program is maintained after cell division.The second way is the addition of methyl groups to the DNA, mostly at CpG sites, to convert cytosine to 5-methylcytosine. 5-Methylcytosine performs much like a regular cytosine, pairing with a guanine in double-stranded DNA. However, some areas of the genome are methylated more heavily than others, and highly methylated areas tend to be less transcriptionally active, through a mechanism not fully understood. Methylation of cytosines can also persist from the germ line of one of the parents into the zygote, marking the chromosome as being inherited from one parent or the other (genetic imprinting).Mechanisms of heritability of histone state are not well understood; however, much is known about the mechanism of heritability of DNA methylation state during cell division and differentiation. Heritability of methylation state depends on certain enzymes (such as DNMT1) that have a higher affinity for 5-methylcytosine than for cytosine. If this enzyme reaches a "hemimethylated" portion of DNA (where 5-methylcytosine is in only one of the two DNA strands) the enzyme will methylate the other half.
    • Although histone modifications occur throughout the entire sequence, the unstructured N-termini of histones (called histone tails) are particularly highly modified. These modifications include acetylation, methylation, ubiquitylation, phosphorylation, sumoylation, ribosylation and citrullination. Acetylation is the most highly studied of these modifications. For example, acetylation of the K14 and K9 lysines of the tail of histone H3 by histone acetyltransferase enzymes (HATs) is known to regulate transcription in accordance with complementary histone deacetylases.[44]
    • One mode of thinking is that this tendency of acetylation to be associated with "active" transcription is biophysical in nature. Because it normally has a positively charged nitrogen at its end, lysine can bind the negatively charged phosphates of the DNA backbone. The acetylation event converts the positively charged amine group on the side chain into a neutral amide linkage. This removes the positive charge, thus loosening the DNA from the histone. When this occurs, complexes like SWI/SNF and other transcriptional factors can bind to the DNA and allow transcription to occur. This is the "cis" model of the epigenetic function. In other words, changes to the histone tails have a direct effect on the DNA itself.[citation needed ]
    • Another model of epigenetic function is the "trans" model. In this model, changes to the histone tails act indirectly on the DNA. For example, lysine acetylation may create a binding site for chromatin-modifying enzymes (or transcription machinery as well). This chromatin remodeler can then cause changes to the state of the chromatin. Indeed, a bromodomain '' a protein domain that specifically binds acetyl-lysine '' is found in many enzymes that help activate transcription, including the SWI/SNF complex. It may be that acetylation acts in this and the previous way to aid in transcriptional activation.
    • The idea that modifications act as docking modules for related factors is borne out by histone methylation as well. Methylation of lysine 9 of histone H3 has long been associated with constitutively transcriptionally silent chromatin (constitutive heterochromatin). It has been determined that a chromodomain (a domain that specifically binds methyl-lysine) in the transcriptionally repressive protein HP1 recruits HP1 to K9 methylated regions. One example that seems to refute this biophysical model for methylation is that tri-methylation of histone H3 at lysine 4 is strongly associated with (and required for full) transcriptional activation. Tri-methylation, in this case, would introduce a fixed positive charge on the tail.
    • It has been shown that the histone lysine methyltransferase (KMT) is responsible for this methylation activity in the pattern of histones H3 and H4. This enzyme utilizes a catalytically active site called the SET domain (Suppressor of variegation, Enhancer of zeste, Trithorax). The SET domain is a 130-amino acid sequence involved in modulating gene activities. This domain has been demonstrated to bind to the histone tail and causes the methylation of the histone.[45]
    • Differing histone modifications are likely to function in differing ways; acetylation at one position is likely to function differently from acetylation at another position. Also, multiple modifications may occur at the same time, and these modifications may work together to change the behavior of the nucleosome. The idea that multiple dynamic modifications regulate gene transcription in a systematic and reproducible way is called the histone code, although the idea that histone state can be read linearly as a digital information carrier has been largely debunked. One of the best-understood systems that orchestrate chromatin-based silencing is the SIR protein based silencing of the yeast hidden mating-type loci HML and HMR.
    • DNA methylation frequently occurs in repeated sequences, and helps to suppress the expression and mobility of 'transposable elements':[46] Because 5-methylcytosine can be spontaneously deaminated (replacing nitrogen by oxygen) to thymidine, CpG sites are frequently mutated and become rare in the genome, except at CpG islands where they remain unmethylated. Epigenetic changes of this type thus have the potential to direct increased frequencies of permanent genetic mutation. DNA methylation patterns are known to be established and modified in response to environmental factors by a complex interplay of at least three independent DNA methyltransferases, DNMT1, DNMT3a, and DNMT3B, the loss of any of which is lethal in mice.[47] DNMT1 is the most abundant methyltransferase in somatic cells,[48] localizes to replication foci,[49] has a 10''40-fold preference for hemimethylated DNA and interacts with the proliferating cell nuclear antigen (PCNA).[50]
    • By preferentially modifying hemimethylated DNA, DNMT1 transfers patterns of methylation to a newly synthesized strand after DNA replication, and therefore is often referred to as the 'maintenance' methyltransferase.[51] DNMT1 is essential for proper embryonic development, imprinting and X-inactivation.[47][52] To emphasize the difference of this molecular mechanism of inheritance from the canonical Watson-Crick base-pairing mechanism of transmission of genetic information, the term 'Epigenetic templating' was introduced.[53] Furthermore, in addition to the maintenance and transmission of methylated DNA states, the same principle could work in the maintenance and transmission of histone modifications and even cytoplasmic (structural) heritable states.[54]
    • Histones H3 and H4 can also be manipulated through demethylation using histone lysine demethylase (KDM). This recently identified enzyme has a catalytically active site called the Jumonji domain (JmjC). The demethylation occurs when JmjC utilizes multiple cofactors to hydroxylate the methyl group, thereby removing it. JmjC is capable of demethylating mono-, di-, and tri-methylated substrates.[55]
    • Chromosomal regions can adopt stable and heritable alternative states resulting in bistable gene expression without changes to the DNA sequence. Epigenetic control is often associated with alternative covalent modifications of histones.[56] The stability and heritability of states of larger chromosomal regions are suggested to involve positive feedback where modified nucleosomes recruit enzymes that similarly modify nearby nucleosomes.[57] A simplified stochastic model for this type of epigenetics is found here.[58][59]
    • It has been suggested that chromatin-based transcriptional regulation could be mediated by the effect of small RNAs. Small interfering RNAs can modulate transcriptional gene expression via epigenetic modulation of targeted promoters.[60]
    • RNA transcripts [ edit ] Sometimes a gene, after being turned on, transcribes a product that (directly or indirectly) maintains the activity of that gene. For example, Hnf4 and MyoD enhance the transcription of many liver-specific and muscle-specific genes, respectively, including their own, through the transcription factor activity of the proteins they encode. RNA signalling includes differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development.[61] Other epigenetic changes are mediated by the production of different splice forms of RNA, or by formation of double-stranded RNA (RNAi). Descendants of the cell in which the gene was turned on will inherit this activity, even if the original stimulus for gene-activation is no longer present. These genes are often turned on or off by signal transduction, although in some systems where syncytia or gap junctions are important, RNA may spread directly to other cells or nuclei by diffusion. A large amount of RNA and protein is contributed to the zygote by the mother during oogenesis or via nurse cells, resulting in maternal effect phenotypes. A smaller quantity of sperm RNA is transmitted from the father, but there is recent evidence that this epigenetic information can lead to visible changes in several generations of offspring.[62]
    • MicroRNAs [ edit ] MicroRNAs (miRNAs) are members of non-coding RNAs that range in size from 17 to 25 nucleotides. miRNAs regulate a large variety of biological functions in plants and animals.[63] So far, in 2013, about 2000 miRNAs have been discovered in humans and these can be found online in a miRNA database.[64] Each miRNA expressed in a cell may target about 100 to 200 messenger RNAs(mRNAs) that it downregulates.[65] Most of the downregulation of mRNAs occurs by causing the decay of the targeted mRNA, while some downregulation occurs at the level of translation into protein.[66]
    • It appears that about 60% of human protein coding genes are regulated by miRNAs.[67] Many miRNAs are epigenetically regulated. About 50% of miRNA genes are associated with CpG islands,[63] that may be repressed by epigenetic methylation. Transcription from methylated CpG islands is strongly and heritably repressed.[68] Other miRNAs are epigenetically regulated by either histone modifications or by combined DNA methylation and histone modification.[63]
    • mRNA [ edit ] In 2011, it was demonstrated that the methylation of mRNA plays a critical role in human energy homeostasis. The obesity-associated FTO gene is shown to be able to demethylate N6-methyladenosine in RNA.[69][70]
    • sRNAs [ edit ] sRNAs are small (50''250 nucleotides), highly structured, non-coding RNA fragments found in bacteria. They control gene expression including virulence genes in pathogens and are viewed as new targets in the fight against drug-resistant bacteria.[71] They play an important role in many biological processes, binding to mRNA and protein targets in prokaryotes. Their phylogenetic analyses, for example through sRNA''mRNA target interactions or protein binding properties, are used to build comprehensive databases.[72] sRNA-gene maps based on their targets in microbial genomes are also constructed.[73]
    • Prions [ edit ] Prions are infectious forms of proteins. In general, proteins fold into discrete units that perform distinct cellular functions, but some proteins are also capable of forming an infectious conformational state known as a prion. Although often viewed in the context of infectious disease, prions are more loosely defined by their ability to catalytically convert other native state versions of the same protein to an infectious conformational state. It is in this latter sense that they can be viewed as epigenetic agents capable of inducing a phenotypic change without a modification of the genome.[74]
    • Fungal prions are considered by some to be epigenetic because the infectious phenotype caused by the prion can be inherited without modification of the genome. PSI+ and URE3, discovered in yeast in 1965 and 1971, are the two best studied of this type of prion.[75][76] Prions can have a phenotypic effect through the sequestration of protein in aggregates, thereby reducing that protein's activity. In PSI+ cells, the loss of the Sup35 protein (which is involved in termination of translation) causes ribosomes to have a higher rate of read-through of stop codons, an effect that results in suppression of nonsense mutations in other genes.[77] The ability of Sup35 to form prions may be a conserved trait. It could confer an adaptive advantage by giving cells the ability to switch into a PSI+ state and express dormant genetic features normally terminated by stop codon mutations.[78][79][80][81]
    • Structural inheritance [ edit ] In ciliates such as Tetrahymena and Paramecium, genetically identical cells show heritable differences in the patterns of ciliary rows on their cell surface. Experimentally altered patterns can be transmitted to daughter cells. It seems existing structures act as templates for new structures. The mechanisms of such inheritance are unclear, but reasons exist to assume that multicellular organisms also use existing cell structures to assemble new ones.[82][83][84]
    • Nucleosome positioning [ edit ] Eukaryotic genomes have numerous nucleosomes. Nucleosome position is not random, and determine the accessibility of DNA to regulatory proteins. Promoters active in different tissues have been shown to have different nucleosome positioning features.[85] This determines differences in gene expression and cell differentiation. It has been shown that at least some nucleosomes are retained in sperm cells (where most but not all histones are replaced by protamines). Thus nucleosome positioning is to some degree inheritable. Recent studies have uncovered connections between nucleosome positioning and other epigenetic factors, such as DNA methylation and hydroxymethylation.[86]
    • Functions and consequences [ edit ] Development [ edit ] Developmental epigenetics can be divided into predetermined and probabilistic epigenesis. Predetermined epigenesis is a unidirectional movement from structural development in DNA to the functional maturation of the protein. "Predetermined" here means that development is scripted and predictable. Probabilistic epigenesis on the other hand is a bidirectional structure-function development with experiences and external molding development.[87]
    • Somatic epigenetic inheritance, particularly through DNA and histone covalent modifications and nucleosome repositioning, is very important in the development of multicellular eukaryotic organisms.[86] The genome sequence is static (with some notable exceptions), but cells differentiate into many different types, which perform different functions, and respond differently to the environment and intercellular signaling. Thus, as individuals develop, morphogens activate or silence genes in an epigenetically heritable fashion, giving cells a memory. In mammals, most cells terminally differentiate, with only stem cells retaining the ability to differentiate into several cell types ("totipotency" and "multipotency"). In mammals, some stem cells continue producing newly differentiated cells throughout life, such as in neurogenesis, but mammals are not able to respond to loss of some tissues, for example, the inability to regenerate limbs, which some other animals are capable of. Epigenetic modifications regulate the transition from neural stem cells to glial progenitor cells (for example, differentiation into oligodendrocytes is regulated by the deacetylation and methylation of histones.[88] Unlike animals, plant cells do not terminally differentiate, remaining totipotent with the ability to give rise to a new individual plant. While plants do utilize many of the same epigenetic mechanisms as animals, such as chromatin remodeling, it has been hypothesized that some kinds of plant cells do not use or require "cellular memories", resetting their gene expression patterns using positional information from the environment and surrounding cells to determine their fate.[89]
    • Epigenetic changes can occur in response to environmental exposure '' for example, maternal dietary supplementation with genistein (250 mg/kg) have epigenetic changes affecting expression of the agouti gene, which affects their fur color, weight, and propensity to develop cancer.[90][91][92]
    • Controversial results from one study suggested that traumatic experiences might produce an epigenetic signal that is capable of being passed to future generations. Mice were trained, using foot shocks, to fear a cherry blossom odor. The investigators reported that the mouse offspring had an increased aversion to this specific odor.[93][94] They suggested epigenetic changes that increase gene expression, rather than in DNA itself, in a gene, M71, that governs the functioning of an odor receptor in the nose that responds specifically to this cherry blossom smell. There were physical changes that correlated with olfactory (smell) function in the brains of the trained mice and their descendants. Several criticisms were reported, including the study's low statistical power as evidence of some irregularity such as bias in reporting results.[95] Due to limits of sample size, there is a probability that an effect will not be demonstrated to within statistical significance even if it exists. The criticism suggested that the probability that all the experiments reported would show positive results if an identical protocol was followed, assuming the claimed effects exist, is merely 0.4%. The authors also did not indicate which mice were siblings, and treated all of the mice as statistically independent.[96] The original researchers pointed out negative results in the paper's appendix that the criticism omitted in its calculations, and undertook to track which mice were siblings in the future.[97]
    • Transgenerational [ edit ] Epigenetic mechanisms were a necessary part of the evolutionary origin of cell differentiation.[98] Although epigenetics in multicellular organisms is generally thought to be a mechanism involved in differentiation, with epigenetic patterns "reset" when organisms reproduce, there have been some observations of transgenerational epigenetic inheritance (e.g., the phenomenon of paramutation observed in maize). Although most of these multigenerational epigenetic traits are gradually lost over several generations, the possibility remains that multigenerational epigenetics could be another aspect to evolution and adaptation.As mentioned above, some define epigenetics as heritable.
    • A sequestered germ line or Weismann barrier is specific to animals, and epigenetic inheritance is more common in plants and microbes. Eva Jablonka, Marion J. Lamb and ‰tienne Danchin have argued that these effects may require enhancements to the standard conceptual framework of the modern synthesis and have called for an extended evolutionary synthesis.[99][100][101] Other evolutionary biologists, such as John Maynard Smith, have incorporated epigenetic inheritance into population genetics models[102] or are openly skeptical of the extended evolutionary synthesis (Michael Lynch).[103] Thomas Dickins and Qazi Rahman state that epigenetic mechanisms such as DNA methylation and histone modification are genetically inherited under the control of natural selection and therefore fit under the earlier "modern synthesis".[104]
    • Two important ways in which epigenetic inheritance can be different from traditional genetic inheritance, with important consequences for evolution, are that rates of epimutation can be much faster than rates of mutation[105] and the epimutations are more easily reversible.[106] In plants, heritable DNA methylation mutations are 100,000 times more likely to occur compared to DNA mutations.[107] An epigenetically inherited element such as the PSI+ system can act as a "stop-gap", good enough for short-term adaptation that allows the lineage to survive for long enough for mutation and/or recombination to genetically assimilate the adaptive phenotypic change.[108] The existence of this possibility increases the evolvability of a species.
    • More than 100 cases of transgenerational epigenetic inheritance phenomena have been reported in a wide range of organisms, including prokaryotes, plants, and animals.[109] For instance, mourning cloak butterflies will change color through hormone changes in response to experimentation of varying temperatures.[110]
    • The filamentous fungus Neurospora crassa is a prominent model system for understanding the control and function of cytosine methylation. In this organism, DNA methylation is associated with relics of a genome defense system called RIP (repeat-induced point mutation) and silences gene expression by inhibiting transcription elongation.[111]
    • The yeast prion PSI is generated by a conformational change of a translation termination factor, which is then inherited by daughter cells. This can provide a survival advantage under adverse conditions. This is an example of epigenetic regulation enabling unicellular organisms to respond rapidly to environmental stress. Prions can be viewed as epigenetic agents capable of inducing a phenotypic change without modification of the genome.[112]
    • Direct detection of epigenetic marks in microorganisms is possible with single molecule real time sequencing, in which polymerase sensitivity allows for measuring methylation and other modifications as a DNA molecule is being sequenced.[113] Several projects have demonstrated the ability to collect genome-wide epigenetic data in bacteria.[114][115][116][117]
    • Epigenetics in bacteria [ edit ] Escherichia coli bacteria
    • While epigenetics is of fundamental importance in eukaryotes, especially metazoans, it plays a different role in bacteria. Most importantly, eukaryotes use epigenetic mechanisms primarily to regulate gene expression which bacteria rarely do. However, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. Bacteria also use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation is important in bacteria virulence in organisms such as Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella. In Alphaproteobacteria, methylation of adenine regulates the cell cycle and couples gene transcription to DNA replication. In Gammaproteobacteria, adenine methylation provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage, transposase activity and regulation of gene expression.[112][118] There exists a genetic switch controlling Streptococcus pneumoniae (the pneumococcus) that allows the bacterium to randomly change its characteristics into six alternative states that could pave the way to improved vaccines. Each form is randomly generated by a phase variable methylation system. The ability of the pneumococcus to cause deadly infections is different in each of these six states. Similar systems exist in other bacterial genera.[119] In Firmicutes such as Clostridioides difficile, adenine methylation regulates sporulation, biofilm formation and host-adaptation.[120]
    • Medicine [ edit ] Epigenetics has many and varied potential medical applications.[121] In 2008, the National Institutes of Health announced that $190 million had been earmarked for epigenetics research over the next five years. In announcing the funding, government officials noted that epigenetics has the potential to explain mechanisms of aging, human development, and the origins of cancer, heart disease, mental illness, as well as several other conditions. Some investigators, like Randy Jirtle, Ph.D., of Duke University Medical Center, think epigenetics may ultimately turn out to have a greater role in disease than genetics.[122]
    • Twins [ edit ] Direct comparisons of identical twins constitute an optimal model for interrogating environmental epigenetics. In the case of humans with different environmental exposures, monozygotic (identical) twins were epigenetically indistinguishable during their early years, while older twins had remarkable differences in the overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation.[8] The twin pairs who had spent less of their lifetime together and/or had greater differences in their medical histories were those who showed the largest differences in their levels of 5-methylcytosine DNA and acetylation of histones H3 and H4.[123]
    • Dizygotic (fraternal) and monozygotic (identical) twins show evidence of epigenetic influence in humans.[123][124][125] DNA sequence differences that would be abundant in a singleton-based study do not interfere with the analysis. Environmental differences can produce long-term epigenetic effects, and different developmental monozygotic twin subtypes may be different with respect to their susceptibility to be discordant from an epigenetic point of view.[126]
    • A high-throughput study, which denotes technology that looks at extensive genetic markers, focused on epigenetic differences between monozygotic twins to compare global and locus-specific changes in DNA methylation and histone modifications in a sample of 40 monozygotic twin pairs.[123] In this case, only healthy twin pairs were studied, but a wide range of ages was represented, between 3 and 74 years. One of the major conclusions from this study was that there is an age-dependent accumulation of epigenetic differences between the two siblings of twin pairs. This accumulation suggests the existence of epigenetic "drift". Epigenetic drift is the term given to epigenetic modifications as they occur as a direct function with age. While age is a known risk factor for many diseases, age-related methylationhas been found to occur differentially at specific sites along the genome. Over time, this can result in measurable differences between biological and chronological age. Epigenetic changes have been found to be reflective of lifestyle and may act as functional biomarkers of disease before clinical threshold is reached.[127]
    • A more recent study, where 114 monozygotic twins and 80 dizygotic twins were analyzed for the DNA methylation status of around 6000 unique genomic regions, concluded that epigenetic similarity at the time of blastocyst splitting may also contribute to phenotypic similarities in monozygotic co-twins. This supports the notion that microenvironment at early stages of embryonic development can be quite important for the establishment of epigenetic marks.[128]Congenital genetic disease is well understood and it is clear that epigenetics can play a role, for example, in the case of Angelman syndrome and Prader-Willi syndrome. These are normal genetic diseases caused by gene deletions or inactivation of the genes but are unusually common because individuals are essentially hemizygous because of genomic imprinting, and therefore a single gene knock out is sufficient to cause the disease, where most cases would require both copies to be knocked out.[129]
    • Genomic imprinting [ edit ] Some human disorders are associated with genomic imprinting, a phenomenon in mammals where the father and mother contribute different epigenetic patterns for specific genomic loci in their germ cells.[130] The best-known case of imprinting in human disorders is that of Angelman syndrome and Prader-Willi syndrome '' both can be produced by the same genetic mutation, chromosome 15q partial deletion, and the particular syndrome that will develop depends on whether the mutation is inherited from the child's mother or from their father.[131] This is due to the presence of genomic imprinting in the region. Beckwith-Wiedemann syndrome is also associated with genomic imprinting, often caused by abnormalities in maternal genomic imprinting of a region on chromosome 11.
    • Rett syndrome is underlain by mutations in the MECP2 gene despite no large-scale changes in expression of MeCP2 being found in microarray analyses. BDNF is downregulated in the MECP2 mutant resulting in Rett syndrome.
    • In the –verkalix study, paternal (but not maternal) grandsons[132] of Swedish men who were exposed during preadolescence to famine in the 19th century were less likely to die of cardiovascular disease. If food was plentiful, then diabetes mortality in the grandchildren increased, suggesting that this was a transgenerational epigenetic inheritance.[133] The opposite effect was observed for females '' the paternal (but not maternal) granddaughters of women who experienced famine while in the womb (and therefore while their eggs were being formed) lived shorter lives on average.[134]
    • Cancer [ edit ] A variety of epigenetic mechanisms can be perturbed in different types of cancer. Epigenetic alterations of DNA repair genes or cell cycle control genes are very frequent in sporadic (non-germ line) cancers, being significantly more common than germ line (familial) mutations in these sporadic cancers.[135][136] Epigenetic alterations are important in cellular transformation to cancer, and their manipulation holds great promise for cancer prevention, detection, and therapy.[137][138] Several medications which have epigenetic impact are used in several of these diseases. These aspects of epigenetics are addressed in cancer epigenetics.
    • Diabetic wound healing [ edit ] Epigenetic modifications have given insight into the understanding of the pathophysiology of different disease conditions. Though, they are strongly associated with cancer, their role in other pathological conditions are of equal importance. It appears that the hyperglycaemic environment could imprint such changes at the genomic level, that macrophages are primed towards a pro-inflammatory state and could fail to exhibit any phenotypic alteration towards the pro-healing type. This phenomenon of altered Macrophage Polarization is mostly associated with all the diabetic complications in a clinical set-up. As of 2018, several reports reveal the relevance of different epigenetic modifications with respect to diabetic complications. Sooner or later, with the advancements in biomedical tools, the detection of such biomarkers as prognostic and diagnostic tools in patients could possibly emerge out as alternative approaches. It is noteworthy to mention here that the use of epigenetic modifications as therapeutic targets warrant extensive preclinical as well as clinical evaluation prior to use.[139]
    • Examples of drugs altering gene expression from epigenetic events [ edit ] The use of beta-lactam antibiotics can alter glutamate receptor activity and the action of cyclosporine on multiple transcription factors. Additionally, lithium can impact autophagy of aberrant proteins, and opioid drugs via chronic use can increase the expression of genes associated with addictive phenotypes.[140]
    • Psychology and psychiatry [ edit ] Early life stress [ edit ] In a groundbreaking 2003 report, Caspi and colleagues demonstrated that in a robust cohort of over one-thousand subjects assessed multiple times from preschool to adulthood, subjects who carried one or two copies of the short allele of the serotonin transporter promoter polymorphism exhibited higher rates of adult depression and suicidality when exposed to childhood maltreatment when compared to long allele homozygotes with equal ELS exposure.[141]
    • Parental nutrition, in utero exposure to stress, male-induced maternal effects such as the attraction of differential mate quality, and maternal as well as paternal age, and offspring gender could all possibly influence whether a germline epimutation is ultimately expressed in offspring and the degree to which intergenerational inheritance remains stable throughout posterity.[142]
    • Addiction [ edit ] Addiction is a disorder of the brain's reward system which arises through transcriptional and neuroepigenetic mechanisms and occurs over time from chronically high levels of exposure to an addictive stimulus (e.g., morphine, cocaine, sexual intercourse, gambling, etc.).[143][144][145][146] Transgenerational epigenetic inheritance of addictive phenotypes has been noted to occur in preclinical studies.[147][148]
    • Anxiety [ edit ] Transgenerational epigenetic inheritance of anxiety-related phenotypes has been reported in a preclinical study using mice.[149] In this investigation, transmission of paternal stress-induced traits across generations involved small non-coding RNA signals transmitted via the male germline.
    • Depression [ edit ] Epigenetic inheritance of depression-related phenotypes has also been reported in a preclinical study.[149] Inheritance of paternal stress-induced traits across generations involved small non-coding RNA signals transmitted via the paternal germline.
    • Fear conditioning [ edit ] Studies on mice have shown that certain conditional fears can be inherited from either parent. In one example, mice were conditioned to fear a strong scent, acetophenone, by accompanying the smell with an electric shock. Consequently, the mice learned to fear the scent of acetophenone alone. It was discovered that this fear could be passed down to the mice offspring. Despite the offspring never experiencing the electric shock themselves the mice still displayed a fear of the acetophenone scent, because they inherited the fear epigenetically by site-specific DNA methylation. These epigenetic changes lasted up to two generations without reintroducing the shock.[150]
    • Research [ edit ] The two forms of heritable information, namely genetic and epigenetic, are collectively denoted as dual inheritance. Members of the APOBEC/AID family of cytosine deaminases may concurrently influence genetic and epigenetic inheritance using similar molecular mechanisms, and may be a point of crosstalk between these conceptually compartmentalized processes.[151]
    • Fluoroquinolone antibiotics induce epigenetic changes in mammalian cells through iron chelation. This leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor.[152]
    • Various pharmacological agents are applied for the production of induced pluripotent stem cells (iPSC) or maintain the embryonic stem cell (ESC) phenotypic via epigenetic approach. Adult stem cells like bone marrow stem cells have also shown a potential to differentiate into cardiac competent cells when treated with G9a histone methyltransferase inhibitor BIX01294.[153][154]
    • Pseudoscience [ edit ] Due to epigenetics being in the early stages of development as a science and the sensationalism surrounding it in the public media, David Gorski and geneticist Adam Rutherford advised caution against proliferation of false and pseudoscientific conclusions by new age authors who make unfounded suggestions that a person's genes and health can be manipulated by mind control. Misuse of the scientific term by quack authors has produced misinformation among the general public.[2][155][156]
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Harvey, Exercitationes 1651, p. 148, and in the English Anatomical Exercitations 1653, p. 272. It is explained to mean 'partium super-exorientium additamentum', 'the additament of parts budding one out of another'." ^ Waddington CH (1942). "The epigenotype". Endeavour. 1: 18''20. "For the purpose of a study of inheritance, the relation between phenotypes and genotypes [...] is, from a wider biological point of view, of crucial importance, since it is the kernel of the whole problem of development. Many geneticists have recognized this and attempted to discover the processes involved in the mechanism by which the genes of the genotype bring about phenotypic effects. The first step in such an enterprise is '' or rather should be, since it is often omitted by those with an undue respect for the powers of reason '' to describe what can be seen of the developmental processes. For enquiries of this kind, the word 'phenogenetics' was coined by Haecker [1918, Ph¤nogenetik]. 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The formation of Î--FosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for Î--FosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of Î--FosB have been opened by epigenetic studies, and recent advances have illustrated the role of Î--FosB acting on DNA and histones, truly as a ''molecular switch'' (34). 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This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken ... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on Î--FosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for Î--FosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks Î--FosB transcription ^ Vassoler FM, Sadri-Vakili G (April 2014). "Mechanisms of transgenerational inheritance of addictive-like behaviors". Neuroscience. 264: 198''206. doi:10.1016/j.neuroscience.2013.07.064. PMC 3872494 . PMID 23920159. ^ Yuan TF, Li A, Sun X, Ouyang H, Campos C, Rocha NB, et al. (November 2016). "Transgenerational Inheritance of Paternal Neurobehavioral Phenotypes: Stress, Addiction, Ageing and Metabolism". Molecular Neurobiology. 53 (9): 6367''6376. doi:10.1007/s12035-015-9526-2. hdl:10400.22/7331. PMID 26572641. ^ a b Short AK, Fennell KA, Perreau VM, Fox A, O'Bryan MK, Kim JH, et al. (June 2016). "Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring". Translational Psychiatry. 6 (6): e837. doi:10.1038/tp.2016.109. PMC 4931607 . PMID 27300263. ^ Szyf M (January 2014). "Lamarck revisited: epigenetic inheritance of ancestral odor fear conditioning". Nature Neuroscience. 17 (1): 2''4. doi:10.1038/nn.3603. PMID 24369368. ^ Chahwan R, Wontakal SN, Roa S (October 2010). "Crosstalk between genetic and epigenetic information through cytosine deamination". Trends in Genetics. 26 (10): 443''8. doi:10.1016/j.tig.2010.07.005. PMID 20800313. ^ Badal S, Her YF, Maher LJ (September 2015). "Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells". The Journal of Biological Chemistry. 290 (36): 22287''97. doi:10.1074/jbc.M115.671222. PMC 4571980 . PMID 26205818. ^ Mezentseva NV, Yang J, Kaur K, Iaffaldano G, R(C)mond MC, Eisenberg CA, Eisenberg LM (February 2013). "The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells". Stem Cells and Development. 22 (4): 654''67. doi:10.1089/scd.2012.0181. PMC 3564468 . PMID 22994322. ^ Yang J, Kaur K, Ong LL, Eisenberg CA, Eisenberg LM (2015). "Inhibition of G9a Histone Methyltransferase Converts Bone Marrow Mesenchymal Stem Cells to Cardiac Competent Progenitors". Stem Cells International. 2015: 270428. doi:10.1155/2015/270428. PMC 4454756 . PMID 26089912. ^ Gorski, David (4 February 2013). "Epigenetics: It doesn't mean what quacks think it means". Science-Based Medicine. ^ Rutherford, Adam (19 July 2015). "Beware the pseudo gene genies". The Observer. Epigenetics is a real and important part of biology, but due to predictable quackery, it is threatening to become the new quantum. Further reading [ edit ] Haque FN, Gottesman II, Wong AH (May 2009). "Not really identical: epigenetic differences in monozygotic twins and implications for twin studies in psychiatry". American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. 151C (2): 136''41. doi:10.1002/ajmg.c.30206. PMID 19378334. External links [ edit ] Look up epigenetics in Wiktionary, the free dictionary."Epigenetics & Inheritance". learn.genetics.utah.edu . Retrieved 17 April 2019 . The Human Epigenome Project (HEP)The Epigenome Network of Excellence (NoE)Canadian Epigenetics, Environment and Health Research Consortium (CEEHRC)The Epigenome Network of Excellence (NoE) '' public international site"DNA Is Not Destiny" '' Discover magazine cover story"The Ghost In Your Genes", Horizon (2005), BBCEpigenetics article at Hopkins MedicineTowards a global map of epigenetic variation
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  • Nocebo - Wikipedia
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    • Harmless substance that creates harmful effects in a patient who takes it
    • A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the treatment to have a more negative effect than it otherwise would have. For example, when a patient anticipates a side effect of a medication, they can suffer that effect even if the "medication" is actually an inert substance. The complementary concept, the placebo effect, is said to occur when positive expectations improve an outcome. Both placebo and nocebo effects are presumably psychogenic, but they can induce measurable changes in the body. One article that reviewed 31 studies on nocebo effects reported a wide range of symptoms that could manifest as nocebo effects including nausea, stomach pains, itching, bloating, depression, sleep problems, loss of appetite, sexual dysfunction and severe hypotension.
    • Etymology and usage [ edit ] The term nocebo (Latin nocÄ'bō, "I shall harm", from noceō, "I harm")[3] was coined by Walter Kennedy in 1961 to denote the counterpart to the use of placebo (Latin placÄ'bō, "I shall please", from placeō, "I please";[4] a substance that may produce a beneficial, healthful, pleasant, or desirable effect). Kennedy emphasized that his use of the term "nocebo" refers strictly to a subject-centered response, a quality inherent in the patient rather than in the remedy". That is, Kennedy rejected the use of the term for pharmacologically induced negative side effects such as the ringing in the ears caused by quinine. That is not to say that the patient's psychologically induced response may not include physiological effects. For example, an expectation of pain may induce anxiety, which in turn causes the release of cholecystokinin, which facilitates pain transmission.
    • Response [ edit ] In the narrowest sense, a nocebo response occurs when a drug-trial subject's symptoms are worsened by the administration of an inert, sham, or dummy (simulator) treatment, called a placebo. According to current pharmacological knowledge and the current understanding of cause and effect, a placebo contains no chemical (or any other agent) that could possibly cause any of the observed worsening in the subject's symptoms. Thus, any change for the worse must be due to some subjective factor. Adverse expectations can also cause the analgesic effects of anesthetic medications to disappear.
    • The worsening of the subject's symptoms or reduction of beneficial effects is a direct consequence of their exposure to the placebo, but those symptoms have not been chemically generated by the placebo. Because this generation of symptoms entails a complex of "subject-internal" activities, in the strictest sense, we can never speak in terms of simulator-centered "nocebo effects", but only in terms of subject-centered "nocebo responses". Although some observers attribute nocebo responses (or placebo responses) to a subject's gullibility, there is no evidence that an individual who manifests a nocebo/placebo response to one treatment will manifest a nocebo/placebo response to any other treatment; i.e., there is no fixed nocebo/placebo-responding trait or propensity.[citation needed ]
    • McGlashan, Evans & Orne (1969, p. 319) found no evidence of what they termed a "placebo personality". Also, in a carefully designed study, Lasagna, Mosteller, von Felsinger and Beecher (1954), found that there was no way that any observer could determine, by testing or by interview, which subject would manifest a placebo reaction and which would not. Experiments have shown that no relationship exists between an individual's measured hypnotic susceptibility and their manifestation of nocebo or placebo responses.
    • Effects [ edit ] Side effects of drugs [ edit ] It has been shown that, due to the nocebo effect, warning patients about side effects of drugs can contribute to the causation of such effects, whether the drug is real or not. This effect has been observed in clinical trials: according to a 2013 review, the dropout rate among placebo-treated patients in a meta-analysis of 41 clinical trials of Parkinson's disease treatments was 8.8%. A 2013 review found that nearly 1 out of 20 patients receiving a placebo in clinical trials for depression dropped out due to adverse events, which were believed to have been caused by the nocebo effect. A 2018 review found that half of patients taking placebos in clinical trials report intervention-related adverse events.[16]
    • Electromagnetic hypersensitivity [ edit ] Evidence suggests that the symptoms of electromagnetic hypersensitivity are caused by the nocebo effect.[17][18]
    • Pain [ edit ] Verbal suggestion can cause hyperalgesia (increased sensitivity to pain) and allodynia (perception of a tactile stimulus as painful) as a result of the nocebo effect. Nocebo hyperalgesia is believed to involve the activation of cholecystokinin receptors.
    • Ambiguity of medical usage [ edit ] Stewart-Williams and Podd argue that using the contrasting terms "placebo" and "nocebo" to label inert agents that produce pleasant, health-improving, or desirable outcomes versus unpleasant, health-diminishing, or undesirable outcomes (respectively), is extremely counterproductive. For example, precisely the same inert agents can produce analgesia and hyperalgesia, the first of which, from this definition, would be a placebo, and the second a nocebo.
    • A second problem is that the same effect, such as immunosuppression, may be desirable for a subject with an autoimmune disorder, but be undesirable for most other subjects. Thus, in the first case, the effect would be a placebo, and in the second, a nocebo. A third problem is that the prescriber does not know whether the relevant subjects consider the effects that they experience to be desirable or undesirable until some time after the drugs have been administered. A fourth problem is that the same phenomena are being generated in all the subjects, and these are being generated by the same drug, which is acting in all of the subjects through the same mechanism. Yet because the phenomena in question have been subjectively considered to be desirable to one group but not the other, the phenomena are now being labelled in two mutually exclusive ways (i.e., placebo and nocebo); and this is giving the false impression that the drug in question has produced two different phenomena.
    • Ambiguity of anthropological usage [ edit ] Some people maintain that belief kills (e.g., "voodoo death": Cannon (1942) describes a number of instances from a variety of different cultures) and belief heals (e.g., faith healing). A "self-willed" death (due to voodoo hex, evil eye, pointing the bone procedure, etc.) is an extreme form of a culture-specific syndrome or mass psychogenic illness that produces a particular form of psychosomatic or psychophysiological disorder which results in a psychogenic death. Rubel (1964) spoke of "culture bound" syndromes, which were those "from which members of a particular group claim to suffer and for which their culture provides an etiology, diagnosis, preventive measures, and regimens of healing".
    • Certain anthropologists, such as Robert Hahn and Arthur Kleinman, have extended the placebo/nocebo distinction into this realm in order to allow a distinction to be made between rituals, like faith healing, that are performed in order to heal, cure, or bring benefit (placebo rituals) and others, like "pointing the bone", that are performed in order to kill, injure or bring harm (nocebo rituals). As the meaning of the two inter-related and opposing terms has extended, we now find anthropologists speaking, in various contexts, of nocebo or placebo (harmful or helpful) rituals:
    • that might entail nocebo or placebo (unpleasant or pleasant) procedures;about which subjects might have nocebo or placebo (harmful or beneficial) beliefs;that are delivered by operators that might have nocebo or placebo (pathogenic, disease-generating or salutogenic, health-promoting) expectations;that are delivered to subjects that might have nocebo or placebo (negative, fearful, despairing or positive, hopeful, confident) expectations about the ritual;which are delivered by operators who might have nocebo or placebo (malevolent or benevolent) intentions, in the hope that the rituals will generate nocebo or placebo (lethal, injurious, harmful or restorative, curative, healthy) outcomes; and, that all of this depends upon the operator's overall beliefs in the harmful nature of the nocebo ritual or the beneficial nature of the placebo ritual.Yet, it may become even more terminologically complex; for, as Hahn and Kleinman indicate, there can also be cases where there are paradoxical nocebo outcomes from placebo rituals (e.g. the TGN1412 drug trial[27][28]), as well as paradoxical placebo outcomes from nocebo rituals (see also unintended consequences). Writing from his extensive experience of treating cancer (including more than 1,000 melanoma cases) at Sydney Hospital, Milton (1973) warned of the impact of the delivery of a prognosis, and how many of his patients, upon receiving their prognosis, simply turned their face to the wall and died a premature death: "there is a small group of patients in whom the realization of impending death is a blow so terrible that they are quite unable to adjust to it, and they die rapidly before the malignancy seems to have developed enough to cause death. This problem of self-willed death is in some ways analogous to the death produced in primitive peoples by witchcraft ('pointing the bone')".
    • See also [ edit ] Notes [ edit ] References [ edit ] Barber, Theodore Xenophon (1961). "Death by suggestion. A critical note". Psychosomatic Medicine. 23: 153''5. doi:10.1097/00006842-196103000-00006. PMID 13686785. Barker, J.C. (1968). Scared to Death: An Examination of Fear, its Cause and Effects. London: Frederick Muller. Barrett, G. V.; Franke, R. H. (1970). " ' Psychogenic' Death: A Reappraisal". Science. 167 (3916): 304''306. Bibcode:1970Sci...167..304B. doi:10.1126/science.167.3916.304. Barsky, Arthur J.; Saintfort, R.; Rogers, M. P.; Borus, J. F. (2002). "Nonspecific Medication Side Effects and the Nocebo Phenomenon". JAMA. 287 (5): 622''7. doi:10.1001/jama.287.5.622. PMID 11829702. Benedetti, F.; Lanotte, M.; Lopiano, L.; Colloca, L. (2007). "When words are painful: Unraveling the mechanisms of the nocebo effect". Neuroscience. 147 (2): 260''271. doi:10.1016/j.neuroscience.2007.02.020. PMID 17379417. Cannon, Walter B. (1942). " ' Voodoo' Death". American Anthropologist. 44 (2): 169''181. doi:10.1525/aa.1942.44.2.02a00010. Charcot, J.M. (January 1893). "The Faith-Cure". The New Review. 8 (44): 18''31. Cohen, Sanford I. (1985). "Psychosomatic death: Voodoo death in a modern perspective". Integrative Psychiatry. 3 (1): 46''51. Colloca, Luana; Miller, Franklin G. (2011). "The Nocebo Effect and its Relevance for Clinical Practice". Psychosomatic Medicine. 73 (7): 598''603. doi:10.1097/PSY.0b013e3182294a50. PMC 3167012 . PMID 21862825. Colloca, Luana; Benedetti, Fabrizio (2007). "Nocebo hyperalgesia: How anxiety is turned into pain". Current Opinion in Anesthesiology. 20 (5): 435''439. doi:10.1097/aco.0b013e3282b972fb. PMID 17873596. Dein, Simon (2003). "Psychogenic death: Individual effects of sorcery and taboo violation". Mental Health, Religion & Culture. 6 (3): 195''202. doi:10.1080/13674670310001633478. Blasi, Zelda Di; Harkness, Elaine; Ernst, Edzard; Georgiou, Amanda; Kleijnen, Jos (2001). "Influence of context effects on health outcomes: A systematic review". The Lancet. 357 (9258): 757''762. doi:10.1016/S0140-6736(00)04169-6. PMID 11253970. Enck, Paul; Benedetti, Fabrizio; Schedlowski, Manfred (2008). "New Insights into the Placebo and Nocebo Responses". Neuron. 59 (2): 195''206. doi:10.1016/j.neuron.2008.06.030. PMID 18667148. Enck, Paul; H¤user, Winfried (10 August 2012). "Beware the Nocebo Effect". The New York Times. Goddard, Henry H. (1899). "The Effects of Mind on Body as Evidenced by Faith Cures". The American Journal of Psychology. 10 (3): 431''502. doi:10.2307/1412143. JSTOR 1412143. Hahn, Robert A. (1997). "The Nocebo Phenomenon: Concept, Evidence, and Implications for Public Health". Preventive Medicine. 26 (5): 607''611. doi:10.1006/pmed.1996.0124. PMID 9327466. Hahn, Robert A.; Kleinman, Arthur (1983). "Perspectives of the Placebo Phenomenon: Belief as Pathogen, Belief as Medicine: 'Voodoo Death' and the 'Placebo Phenomenon' in Anthropological Perspective". Medical Anthropology Quarterly. 14 (4): 3''19. doi:10.1525/maq.1983.14.4.02a00030. Harrington, E.R. (1998), The Nocebo Effect: A Meta-Analysis of the Effect of Suggestion on Reports of Physical Symptoms (Ph.D. Dissertation), Temple University H¤user, Winfried; Hansen, Ernil; Enck, Paul (2012). "Nocebo Phenomena in Medicine". Deutsches Aerzteblatt Online. 109 (26): 459''65. doi:10.3238/arztebl.2012.0459. PMC 3401955 . PMID 22833756. Houston, W. R. (1938). "The Doctor Himself as a Therapeutic Agent". Annals of Internal Medicine. 11 (8): 1416. doi:10.7326/0003-4819-11-8-1416. Kennedy, WP (1961). "The nocebo reaction". Medical World. 95: 203''5. PMID 13752532. Kirsch, Irving (1985). "Response expectancy as a determinant of experience and behavior". American Psychologist. 40 (11): 1189''1202. doi:10.1037/0003-066X.40.11.1189. Kirsch, Irving (1997). "Response expectancy theory and application: A decennial review". Applied and Preventive Psychology. 6 (2): 69''79. doi:10.1016/S0962-1849(05)80012-5. Lasagna, Louis; Mosteller, Frederick; von Felsinger, John M.; Beecher, Henry K. (1954). "A study of the placebo response". The American Journal of Medicine. 16 (6): 770''779. doi:10.1016/0002-9343(54)90441-6. PMID 13158365. Lorenz, J¼rgen; Hauck, Michael; Paur, Robert C.; Nakamura, Yoko; Zimmermann, Roger; Bromm, Burkhart; Engel, Andreas K. (2005). "Cortical correlates of false expectations during pain intensity judgments'--a possible manifestation of placebo/nocebo cognitions". Brain, Behavior, and Immunity. 19 (4): 283''295. doi:10.1016/j.bbi.2005.03.010. PMID 15890494. McGlashan, Thomas; Evans, Frederick J.; Orne, Martin (May 1969). "The nature of hypnotic analgesia and placebo response to experimental pain". Psychosomatic Medicine. 31 (3): 227''46. doi:10.1097/00006842-196905000-00003. PMID 4892726. Merton, Robert K. (1936). "The Unanticipated Consequences of Purposive Social Action". American Sociological Review. 1 (6): 894''904. doi:10.2307/2084615. JSTOR 2084615. Miller, Franklin G. (2005). "William James, Faith, and the Placebo Effect". Perspectives in Biology and Medicine. 48 (2): 273''281. doi:10.1353/pbm.2005.0059. PMID 15834199. Miller, Franklin G. (2003). "Sham Surgery: An Ethical Analysis". The American Journal of Bioethics. 3 (4): 41''48. doi:10.1162/152651603322614580. PMID 14744332. Milton, G.W. (1973). "Self-Willed Death or the Bone-Pointing Syndrome". The Lancet. 301 (7817): 1435''1436. doi:10.1016/S0140-6736(73)91754-6. PMID 4122997. Mitsikostas, Dimos D.; Mantonakis, Leonidas; Chalarakis, Nikolaos (2014). "Nocebo in clinical trials for depression: A meta-analysis". Psychiatry Research. 215 (1): 82''86. doi:10.1016/j.psychres.2013.10.019. PMID 24210741. Murray, Danielle; Stoessl, A. Jon (2013). "Mechanisms and therapeutic implications of the placebo effect in neurological and psychiatric conditions". Pharmacology & Therapeutics. 140 (3): 306''318. doi:10.1016/j.pharmthera.2013.07.009. PMID 23880289. Perlman, Lawrence M. (2001). "Nonspecific, unintended, and serendipitous effects in psychotherapy". Professional Psychology: Research and Practice. 32 (3): 283''288. doi:10.1037/0735-7028.32.3.283. Phillips, D. P.; Liu, G. C.; Kwok, K.; Jarvinen, J. R.; Zhang, W.; Abramson, I. S. (2001). "The Hound of the Baskervilles effect: Natural experiment on the influence of psychological stress on timing of death". BMJ. 323 (7327): 1443''1446. doi:10.1136/bmj.323.7327.1443. PMC 61045 . PMID 11751347. Pyysiainen, Ilkka (2002). "Mind and Miracles". Zygon. 37 (3): 729''740. doi:10.1111/1467-9744.00449. Rief, Winfried; Avorn, Jerry; Barsky, Arthur J. (2006). "Medication-Attributed Adverse Effects in Placebo Groups". Archives of Internal Medicine. 166 (2): 155''60. doi:10.1001/archinte.166.2.155. PMID 16432082. Richter, Curt P. (1957). "On the Phenomenon of Sudden Death in Animals and Man". Psychosomatic Medicine. 19 (3): 191''198. CiteSeerX 10.1.1.536.1405 . doi:10.1097/00006842-195705000-00004. PMID 13432092. R"heim, G (1925). "The Pointing Bone". The Journal of the Royal Anthropological Institute of Great Britain and Ireland. 55: 90''114. doi:10.2307/2843694. JSTOR 2843694. Rubel, Authur J. (1964). "The Epidemiology of a Folk Illness: Susto in Hispanic America". Ethnology. 3 (3): 268''283. doi:10.2307/3772883. JSTOR 3772883. Rubin, G. James; Nieto-Hernandez, Rosa; Wessely, Simon (2009). "Idiopathic environmental intolerance attributed to electromagnetic fields (formerly 'electromagnetic hypersensitivity'): An updated systematic review of provocation studies". Bioelectromagnetics. 31 (1): 1''11. doi:10.1002/bem.20536. PMID 19681059. Shapiro, Arthur K. (2007). "A contribution to a history of the placebo effect". Behavioral Science. 5 (2): 109''135. doi:10.1002/bs.3830050202. Shapiro, Arthur K. (1968). "Semantics of the placebo". The Psychiatric Quarterly. 42 (4): 653''695. doi:10.1007/BF01564309. PMID 4891851. South, Robert (1727). "A Sermon Delivered at Christ-Church, Oxon., Before the University, Octob. 14. 1688: Prov.XII.22 Lying Lips are abomination to the Lord". Twelve Sermons Preached Upon Several Occasions. I (6th ed.). London: J. Bettenham. pp. 458''500. Spiegel, Herbert (1997). "Nocebo: The Power of Suggestibility". Preventive Medicine. 26 (5): 616''621. doi:10.1006/pmed.1997.0229. PMID 9327468. Staats, Peter; Hekmat, Hamid; Staats, Arthur (1998). "Suggestion/Placebo Effects on Pain". Journal of Pain and Symptom Management. 15 (4): 235''243. doi:10.1016/S0885-3924(97)00363-1. PMID 9601159. Stam, Henderikus (1982). "Hypnotic analgesia and the placebo effect; controlling ischemic pain". doi:10.22215/etd/1982-00726. Stam, Henderikus J.; Spanos, Nicholas P. (1987). "Hypnotic analgesia, placebo analgesia, and ischemic pain: The effects of contextual variables". Journal of Abnormal Psychology. 96 (4): 313''320. doi:10.1037/0021-843X.96.4.313. Stathis, P.; Smpiliris, M.; Konitsiotis, S.; Mitsikostas, D. D. (2013). "Nocebo as a potential confounding factor in clinical trials for Parkinson's disease treatment: A meta-analysis". European Journal of Neurology. 20 (3): 527''533. doi:10.1111/ene.12014. PMID 23145482. Stewart-Williams, Steve; Podd, John (2004). "The Placebo Effect: Dissolving the Expectancy Versus Conditioning Debate". Psychological Bulletin. 130 (2): 324''340. doi:10.1037/0033-2909.130.2.324. PMID 14979775. Bingel, U.; Wanigasekera, V.; Wiech, K.; Ni Mhuircheartaigh, R.; Lee, M. C.; Ploner, M.; Tracey, I. (2011). "The Effect of Treatment Expectation on Drug Efficacy: Imaging the Analgesic Benefit of the Opioid Remifentanil". Science Translational Medicine. 3 (70): 70ra14. doi:10.1126/scitranslmed.3001244. PMID 21325618. Wilson, Ian (1991). The Bleeding Mind: An Investigation into the Mysterious Phenomenon of Stigmata. London: Paladin. ISBN 978-0-586-09014-5. Zusne, L.; Jones, W.H. (1989). Anomalistic Psychology: A Study of Magical Thinking (2nd ed.). New York: Lawrence Erlbaum Associates. External links [ edit ] Look up nocebo in Wiktionary, the free dictionary.Nocebo and nocebo effectThe nocebo responseThe Nocebo Effect: Placebo's Evil TwinWhat modifies a healing responseThe science of voodoo: When mind attacks body, New ScientistThe Effect of Treatment Expectation on Drug Efficacy: Imaging the Analgesic Benefit of the Opioid RemifentanilThis Video Will Hurt (The Nocebo Effect) - Video LinkBBC Discovery program on the nocebo effectWhat is the Nocebo effect?
  • Change Your Words and Change Your World | Psychology Today
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    • Note the alternation between the two patterns in her quotes:
    • ''People ask why I didn't leave after I was hit the first time. . . . But you feel such inner turmoil and confusion. You want it to be only one time.''
    • ''And for three days after that incident I did the right thing. I said, 'Don't call me. I never want to see you again.' . . . . But then you start taking his phone calls. Then he asks to see you in person, and you say yes to that. Then you have a big giant man crying like a baby on your lap, and next thing you know, you're consoling him.''
    • The pronoun switching, typically unconscious, has the effect of priming the listener's forgiveness, by projecting the inclination for the same self-defeating behavior upon the listener. ''You might have done the same thing,'' the syntax implies; ''it wasn't my fault.'' This is a fairly typical psychosemantic maneuver of abdication'--surrendering the authority and responsibility to act in one's own self-interest.
    • Listen to people who have power in and over their lives, and compare the language they use to the language of those who, for whatever reason, may feel disempowered. You're likely to hear two subtly different narratives. One is the narrative of cause and effect. The other, figuratively, is the narrative of ''effect and cause.''
    • Getting behind the words for a moment, we can recognize two distinctly different mindsets, or mental states. When someone is at the place of ''cause,'' psychologically speaking, he or she acts from an intention, seeks an outcome, and has a plan, however elementary it might be.
    • And when one is at the place of ''effect,'' one perceives and conceives of himself or herself as on the receiving end of the intentions and actions of others. Things are done to this person, not by them.
    • Let's not over-generalize: Being ''at effect'' has its value at times. When someone is giving you a massage or some other pleasant sensory experience, ''effect'' is a great place to be. Being nurtured, comforted, and cared for can be a very satisfying experience.
    • The strategic choice, moment to moment, is whether to act from the place of cause or the place of effect. On average, you're more powerful in your life when you act and react from the place of cause. Conversely, you may be a victim in your life to the extent that you refuse to take responsibility for your behavior and its consequences. Language behavior is just as real and revealing as any other kind of behavior. It telegraphs its state of origin.
    • So can you really change your attitudes about life just by changing the words you use to frame your thoughts? It might sound a bit simplistic, but consider that the structure of your language is the software of your brain'--or, at least, one important kind of software.
    • Which comes first, a thought or the words that frame it? Many semanticists would claim that they arise simultaneously in the brain. When we habitually say something in a certain way, we're predisposed to think about it in terms of the subtle implications of the words we've chosen. Language evokes thought, and thought evokes language.
    • You might begin by listening more carefully for the subtle cues of cause and effect'--capacity and incapacity'--in the conversations around you. ''My girlfriend treats me like dirt"; ''My parents never let me do what I want to"; "Yes, he has a bad temper, but I can't leave him right now; he needs me"; "I was trying to lose weight, but I fell off the wagon"; "I can't afford that right now.''
    • The language of powerlessness seems to pervade much of the popular culture and its discourse, even its music. And not just today: Remember, one of Frank Sinatra's best-known songs was ''You're Nobody 'til Somebody Loves You.''
    • But today, too many political activists preach a victim narrative to their target audiences. ''Society,'' they tell their listeners, is somehow holding them back, keeping them down, preventing them from participating in the good life. But maybe it's really the speakers, and their disempowering narrative, holding them back.
    • There's a lot more to the psychology of cause and effect, but a good starting point for most of us would be to clean up our language. The famous motivational psychologist Norman Vincent Peale often said, ''Change your thoughts, and you change your world.'' Maybe it's time to update that advice: Change your words, and you change your world.
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  • Sympathetic vomiting is probably a survival trait, in the event someone in the group ate something bad. : Showerthoughts
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    • Mon, 06 Apr 2020 20:59
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    • Edit: Thanks for the Gold, makes me wanna puke!
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    • level 1Ah, spontaneous mass puking. So I'm in my preschool class of five year olds at the white board and Kevin stands up, heaves once, and projectile vomits about two feet onto the floor. Cue four other kids hurking in the next minute. We moved to another room and called the poor janitor. Classroom smelled like Satan's distilled ass juice for weeks. Thanks Kevin.
    • level 2Satans distilled ass juice. Wow
    • level 2Likewise, only his name was Jordan I think. He mumbled something about eating bad milk in his strawberry cereal before splashing said cereal down the aisle as he ran to the back of the room. To this day I cannot eat Special K cereal with the freeze dried strawberries. The smell is burned in my brain literally for life. It's been almost 15 years now.
    • level 2I remember in second grade lunch one of the boys hurked chocolate milk and mashed potatoes on his tray. He was sitting diagonal from me. Yellow snot was hanging from his nose and mouth, dripping viscously onto his ruined food and the lunch table.
    • I gagged several times typing this out on my phone. I'm sure I don't have to say that I hurked as I'd never had to hurk that day, but I just did.
    • level 2I feel your pain here. I was doing a half-day sub job with a 5th grade class. I arrived at the cafeteria to pick them up when I noticed that three of the boys were eating pickles and Red Hot Cheetos. I was informed that the boys in question were having a Hot Cheeto eating contest. I just rolled my eyes and marched the kids down the hall. We got about half way down when I heard the familiar hurking sound, I was about to yell at the offender to go to the bathroom but he projectile vomited Red Hot Cheetos and pickle all over the floor. This triggered the other two Cheeto bad-asses to hurk along with two girls. I ordered the hurkers to the nurse, hurried the rest of the kids to the classroom and then had to run to the office to get the janitor. It was not a good start to the day.
    • level 2As a Kevin who was a very I'll child I apologize. My puke was toxic waste.
    • level 2Why is it always a Kevin??
    • level 2It's times like these that I feel old, but this calls to mind the scene from "Stand By Me", the revenge of 'ol Lard-ass
    • level 2I was so scared of vomit in kindergarten and growing up. Have OCD and even then I had a ritual every morning to make sure nobody would puke that day.
    • level 2I didn't make it past the ''and Kevin stands up" before laughing hysterically.
  • Mass hysteria in upstate New York: Why Lori Brownell and 13 other teenage girls are showing Tourette's-like symptoms.
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    • Mon, 06 Apr 2020 20:58
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    • Last August, 16-year-old Lori Brownell passed out while head-banging at a concert. A month later, she lost consciousness again at her school’s homecoming dance in upstate Corinth, N.Y. Brownell says her doctors put her on Celexa, but she only developed more symptoms, including involuntary twitching and clapping. In videos she posted to YouTube, Brownell flutters her fingers, touches her hair, snorts through her nose and throat, and shouts “Hey, hey, hey,” seemingly without control. On Christmas Eve, doctors diagnosed her with Tourette’s Syndrome. Now, however, her symptoms have another name: conversion disorder, or mass hysteria.
    • Since Brownell first passed out last summer, 14 other upstate New York students—13 girls and a boy, most of them students at LeRoy Junior-Senior High School—have come down with similar symptoms. The young people and their parents seem baffled. The state department of health and a separate report commissioned by the school have found no problematic substances in the building. Environmental activist Erin Brockovich is launching her own investigation into the outbreak; she told USA Today that her prime suspect is a train derailment that dumped cyanide and an industrial solvent in LeRoy in 1970. On Saturday, Brockovich’s team was turned away by the school while trying to collect soil samples on the property.
    • However, a doctor treating many of the students is confident that they are suffering not from poisoning, but from mass hysteria, also called mass psychogenic illness and other variants. Typically, symptoms—which can include Brownell’s Tourette’s-like movements, along with nausea, dizziness, cramping, and more—start with one or two victims and spread when others see or hear about them. Victims are often accused of faking it, but more often they are suffering real physical symptoms that are psychological in origin. The phenomenon has been observed for centuries, with the blame shifting to whatever specific anxieties are culturally pervasive at the time. But one theme has remained consistent: The victims are overwhelmingly female.
    • The most famous American incident of mass hysteria remains the events surrounding the witch trials in Salem, Mass., which began when several girls began suffering mysterious fits and outbursts. In non-Western countries, demons and witchcraft are still sometimes blamed for outbreaks of fainting and fits [PDF]. Pollution, poisoning, chemical weapons, and other environmental concerns are dominant in the West (a fact that makes Brockovich something of a mass hysteria machine). Some bloggers are now claiming that the upstate New York girls fell ill because of the HPV vaccine or fracking.
    • As archetypes go, the Salem events hold up quite well, even from a distance of 320 years. Victims of mass hysteria are so often female that gender imbalance is one clue doctors use to differentiate hysteria from poisoning. Symptoms often start with older girls or women and spread to younger or lower-status girls. As girlhood guardian Caitlin Flanagan put it in the New York Times this weekend, “It is the cheerleaders and not the linebackers who come down with tics and stuttering.” But, as research has shown, it is also the cheerleaders and not the math-club girls who are likely to spread hysteria.
    • In a typical case in 1998, a teacher at a Tennessee high school noticed a gas-like odor in her classroom. The school was quickly evacuated, but the teacher’s symptoms spread to more than 180 teachers and students, who exhibited symptoms including headaches, nausea, and vomiting. By the end of the ordeal, the school had to be closed for two weeks and almost $100,000 was spent on emergency medical care. No toxins were ever found. A later study of the incident in the New England Journal of Medicine—one of surprisingly few on the phenomenon of mass hysteria—found that symptoms were “significantly associated with female sex, seeing another ill person, knowing that a classmate was ill, and reporting an unusual odor at the school.”
    • There’s no consensus about why women and girls are more vulnerable to episodes of mass hysteria. One professor speculated last year that “Stress, boredom, concern about their children and other factors among young females” could have triggered a recent fainting epidemic among female factory workers in Cambodia. Sociologist Robert Bartholomew noted in a 2001 book on mass hysteria that girls are trained to turn their anxieties inward, while anxious boys are likelier to act out. Women are also likelier to seek medical treatment than men.
    • Some scholars have also argued that hysterical episodes allow women to take a break from daily drudgeries, or to rage against patriarchal cultures within the safe bounds of demon possession or poisoning. If girls can find no outlet for reckless abandon, in other words, they’ll create one. Barbara Ehrenreich, Elizabeth Hess, and Gloria Jacobs put it this way in a 1992 essay: “To abandon control—to scream, faint, dash about in mobs—was, in form if not in conscious intent, to protest the sexual repressiveness, the rigid double standard of female teen culture.” They were writing about Beatlemania, as it turns out, but the description of the wildness that overcomes girls in adolescence is almost identical to much scholarly musing about mass hysteria.
    • There is also, it must be noted, a long history of medical professionals dismissing women’s health concerns as mere hysteria. This makes treatment thorny. Sufferers naturally want to be taken seriously, and are often offended by suggestions that their symptoms are “all in their heads.” Several of the upstate New York victims and their families told the Today show that they’re not satisfied with the new diagnosis. “Obviously all of us are not accepting that this is just a stress thing, and our kids didn’t all get sick by coincidence,” one father said. A few cases diagnosed as mass hysteria at the time have later proved to be poisoning after all; a 1990 outbreak of nausea at a British school that affected girls at almost twice the rate of boys turned out to be largely explained by pesticides used on cucumbers served at lunch. But almost always, symptoms disappear on their own over time and no physical causes are discovered.
    • Until more is known about mass hysteria, the treatment of a 1789 case in Northern England might point the way to a cure both effective and enjoyable. The outbreak at a textile factory started when one woman teased another by putting a mouse in her dress; the skittish prank victim fell into convulsions. Soon, however, a rumor spread that an open bag of imported cotton had somehow caused the reaction, and others quickly began falling ill. The factory had to temporarily shut down when 24 people (21 women, two young girls, and one man) experienced violent convulsions so severe they had to be restrained. The plague ended when authorities convinced the patients that symptoms were “merely nervous.” To further tamp down anxieties, sufferers were encouraged to “take a cheerful glass and join in a dance.” The day after the dance, almost all the victims went back to work, their convulsions having disappeared for good.
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  • Corona beer halts production during coronavirus pandemic
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    • Mon, 06 Apr 2020 20:52
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    • (C) / Getty Images Coronavirus Pandemic Causes Climate Of Anxiety And Changing Routines In America A brand that has been in the public eye amid the coronavirus pandemic due to its name announced this week that it is temporarily halting operations. The production of Corona beer is now suspended as it is considered a "non-essential business."
    • Grupo Modelo, the company that produces Corona beer, announced on Twitter Thursday it will stop brewing its beverages starting Sunday after the Mexican government declared breweries non-essential businesses. The brewer, owned by Anheuser-Busch InBev, said it is already in the process of decreasing production.
    • On Tuesday, the Mexican government declared a health emergency, ordering the suspension of all non-essential activities until April 30 to prevent the further spread of the coronavirus. The number of confirmed COVID-19 cases in the country surpassed 1,600 Saturday, with at least 60 deaths, Johns Hopkins University reports.
    • In its announcement, Grupo Modelo appeared to argue that beer should be considered essential under the umbrella of agricultural businesses. The company said that more than 15,000 families benefit each year from the farming of malted barley and 800,000 grocers rely on the sale of beer for about 40% of their income.
    • Grupo Modelo said it has followed strict safety and hygiene measures and would be prepared to have 75% of its staff work from home to "guarantee the supply of beer" if the government changes its mind and confirms beer as an essential agro-industrial product.
    • The brewer also announced it is donating 300,000 antibacterial sanitizers produced from beer '-- a trend growing in popularity among distilleries . It plans to announce further actions to contribute to relief efforts in the coming days.
    • Early on in the pandemic, some consumers mistakenly associated Corona beer with the virus, with an increase in Google searches for "corona beer virus" and "beer virus." And according to one survey , 38% of American beer drinkers said in late February that they would not buy Corona "under any circumstances" at the moment '-- but among regular Corona drinkers, only 4% said the same.
    • Yet 14% of the Corona drinkers admitted they would not order the brand in a public place, according to the survey. 16% of beer drinkers surveyed were confused at the time about whether Corona beer is related to the virus.
    • However, Constellation Brands, which oversees the company's beer in the U.S. said that sales were unaffected by the virus, CNN reports. "We believe that consumers, by and large, understand there's no linkage between the virus and our beer/business," a spokesperson for Constellation Brands told CBS MoneyWatch in late January , well before the virus hit the U.S.
  • Robert Pyatt | Kean University
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    • Mon, 06 Apr 2020 20:35
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    • Jim Henson once said, ''[kids] don't remember what you try to teach them. They remember what you are.'' Nowhere is that better applied than in science education, where we should strive to teach students what science is by immersing them in the scientific process as active participants. They will then leave the classroom better able to analyze, interpret, question and create."
  • Martial Law Defintion
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    • Mon, 06 Apr 2020 20:31
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    • What Is Martial Law? Martial law is a law administered by the military rather than a civilian government. Martial law may be declared in an emergency or response to a crisis, or to control occupied territory.
    • Key Takeaways:Martial law is law administered by the military rather than a civilian government, typically to restore order.Martial law is declared in an emergency, in a response to a crisis, or to control occupied territory.When martial law is declared, civil liberties, such as the right to free movement, free speech, protection from unreasonable searches, and habeas corpus laws may be suspended. Understanding Martial Law The declaration of martial law is a rare and momentous decision for a civilian government to make and for a good reason. When martial law is declared, civilian control of some or all aspects of government operations is ceded to the military. This means that, in the case of elected governments, the representatives chosen by the voting population are no longer in power. Civilians have thus ceded control of the country in exchange for the potential restoration of order with the possibility that control may not be reclaimed in the future.
    • When martial law is declared, civil liberties, such as the right to free movement, free speech or protection from unreasonable searches, can be suspended. The justice system that typically handles issues of criminal and civil law is replaced with a military justice system, such as a military tribunal. Civilians may be arrested for violating curfews or for offenses that, in normal times, would not be considered serious enough to warrant detention. Laws relating to habeas corpus that are designed to prevent unlawful detention may also be suspended, allowing the military to detain individuals indefinitely without the possibility of recourse.
    • Declaring Martial Law Considering the negative ramifications martial law can have on a country and its citizens, declaring martial law is a last resort reserved for situations where law and order is rapidly deteriorating. It may be declared to reign in protests, civil unrest, coup d'(C)tats, or insurrections. Martial law may also be declared when a country's military occupies foreign territory, such as at the end of a war. For example, in 1892, the governor of Idaho instituted martial law after a group of rebellious mine workers blew up a mill, which leveled a four-story building and killed one person.
    • Typically, the power to declare martial law rests with the president. The circumstances in which it may be declared and other limiting factors, such as the amount of time it may be left in effect, are enshrined in legislation or a country's constitution. For example, a president may be authorized to declare martial law during a time of violent civil unrest, but only for 60 days. International laws may also limit the scope and duration of martial law if a country has signed onto a multilateral treaty.
    • Special Considerations'--States of Emergency The use of martial law in the wake of natural disasters is less common. Rather than declare martial law and hand over power to the military in the case of a hurricane or earthquake, governments are much more likely to declare a state of emergency. When a state of emergency is declared, the government may expand its powers or limit the rights of its citizens. The government does not, however, have to hand power over to its military. In some cases, a government may invoke a state of emergency specifically to suppress dissent or opposition groups.

• Music in this episode
  • Intro: Big Pun - Beware
  • Outro: D'Angelo - The Root

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