#Differentially expressed genes

[ohno-the-sun]

Ya know sometimes it’s funny to me

I’m like why do I always write the boys as humans and specifically recently mermaids, why not write them as robots?

And then I look at my backlog of human bio and fish anatomy stuff and I’m like-

Yeah okay I could world-build for hours using this

And on the other hand I am completely in the dark about most programming and robotics things

[airises]

What are induced pluripotent stem cells, and how are they different from embryonic stem cells?

What are induced pluripotent stem cells (iPSCs)? Reprogrammed adult cells: iPSCs are created in the lab by taking adult cells (often skin or blood cells) and genetically reprogramming them back to an immature, embryo-like state. Pluripotency: Like embryonic stem cells, iPSCs are pluripotent. This means they have the exceptional potential to develop into almost any type of cell in the body. Key…

[transmutationisms]

i understand no mental illnesses have been tied to any gene, but my understanding was that there is some evidence on heritability in some cases i.e. for ADHD “many genetic…risks…have a small effect” (doi:10.1016/j.neubiorev.2021.01.022); how are we to understand such findings through a antipsych lens?

okay I just want to be clear because I think a lot of you have a fundamental misunderstanding of what people mean when we self id as 'antipsych.' it's not that 'antipsych' is some sort of pie-in-the-sky theory that I pre-committed to and now have to reconcile with the medical literature—it's more like, I grew up as a very I Fucking Love Science Dot Com child, got interested in psychology among other things, started reading both popular and medical literature about it, started to notice that the things I was reading about psychology and mental diseases didn't really line up with the things I and people I knew experienced and heard when actually interacting with doctors and psychologists, and finally and only around about the age of 19 did I become aware that 'antipsych' is in fact a legitimate position that other people had come up with before me, and at that point I started to read things that you might be referring to here as being written 'through an antipsych lens.'

so, when I hear a question like this, ie one that presumes there is some contradiction between anti-psychiatric political commitments and the existing psychiatric literature, it suggests to me that you haven't really read the literature in question—where by 'read' I mean you need to actually look at the paper's methodology, and look at the process of knowledge-making that yields a sentence like "ADHD has genetic etiology." that's an empirical claim. evaluating whether it's true necessarily involves asking what evidence the person making the claim is offering. there are specific skills and strategies for doing this when you are a layperson dealing with specialised scientific literature; there is also a fundamental critical attitude you should adopt with regards to literally any claim, argument, discourse, article, etc.

it is always a good thing to recognise when you're in over your head and need help or further reading to understand a statistical method, piece of jargon, etc. but you do kind of have to, like, approach the issue with a fundamental attitude that just because someone said something in a scientific journal doesn't make it beyond reproach! read the claims, read the evidence, ask yourself if it makes sense. this isn't some rhetorical game of "I'm going to prove antipsych right"—the 'antipsych' is the loose umbrella term you are called when you actually read the psychiatric literature and critique the discipline's fundamental epistemological failures and disciplinary raison d'être. the horse draws the cart!

wrt 'genetic causes of psychiatric diseases' you also need to understand that many of you are tilting at windmills. I've never said genes don't have an effect on our affective and emotional lives. plainly, they do. this is not the same as "there is a distinct specific Pathology expressed in these genes; they are diseased and/or defective and this is why you feel miserable / cannot function / cannot go to work." like, we see these are two different statements, yes? if all we mean by ADHD is "a list of general behavioural dispositions" then yeah, of course those have genetic influences in addition to environmental ones. everything about us does. that does not mean that ADHD, the distinct and discrete clinical entity that psychiatrists presume exists (on the grounds of their patients having xyz problems), is indeed a 'genetic condition' or instantiates as a genetic mutation / malformation / differential expression / etc. this paragraph is foreshadowing.

having looked at the genetics section of this particular study for about 20 minutes (open-access here if you don't feel like searching by DOI), here are some things that immediately caught my attention:

this is just a meta-analysis of ADHD research. its claims are only as good as the underlying studies. a meta-analysis of shitty studies that had bad methodology will not 'even out' their respective badness, it will just produce a shitty meta-analysis that is intrinsically hampered by the bad underlying methodology. I've discussed this here.

the very first assertion under the genetics section cites three twin studies; I followed those links. first of all, these are written for other scientists, so they don't make a particularly clear (to lay people) distinction between the scientific notion of 'heritability' and what this term is typically interpreted to mean in popular discourses. so, to be clear, 'heritability' is an estimate of how much a given trait is caused by genetic factors at a population level. it does not tell you anything about how much an individual's expression of that trait is genetically caused, nor does heritability necessarily indicate the genetic cause is direct or dependent on one (or even a small number of) genes.

indeed, all three of these studies, and the overarching meta-analysis, assert that this genetic etiology is due to a very large number of very small genetic influences. this is not inherently scientifically unsound, but it does raise my eyebrows. how would we distinguish between a distinct pathology that is caused by a huge tangle of very low-impact genes, vs a whole bunch of behaviours that are socially stigmatised and grouped together on political grounds, and that also have some relationship to genetics, as does literally every physiological fact of human existence?

these cite twin studies, meaning basically they try to use comparisons between genetically identical twins and various other familial relationships to determine how much of a given characteristic is genetically caused. again, though, this is essentially boiling down to the observation that closely genetically related people have similar personality traits; also, twin studies in general have serious methodological problems with profound implications for the invocation of genetics in psychiatry.

in fact, the meta-analysis here also claims that ADHD can sometimes be due to "rare single gene defects" or chromosomal abnormalities. the study cited on the gene claim, for example, is also cited in the claim above, so I've already looked at it. the methodology here is to look at prevalence of ADHD among populations with certain known genetic conditions—that's it. now can we think of any other reasons why people diagnosed with one thing might also be diagnosed with another? for example, they're already in contact with the medical system. they have enough financial resources to seek diagnoses. symptoms of chronic pain & illness often manifest with attention disturbances. etc.

even if that were better founded, the claim they're making themselves here is that ADHD in fact has numerous genetic causes, all manifesting as the same behaviours and psychological disturbances. it's almost like those manifestations are not a single distinct pathology, but a group of 'signs' the clinician lumps together into a single diagnostic box regardless of whence they arise. hold that thought.

incidentally, that study also notes that initial heritability estimates for ADHD were much lower than what's cited now, and blames this on inaccurate self-assessment results, claiming the more recent studies using parent and teacher assessments of ADHD children are more accurate. of course, the actual diagnostic measure never became less 'subjective.' it's just that we trust it more if it's a parent reporting that their kids are all super ADHD than if it's the kid actually reporting their own experiences. because there certainly aren't any historical reasons why parents have felt the need to cling to the notion of a neurobiological, genetically determined distinct ADHD pathology!

similarly, numerous of these linked studies say that 'sub-threshold ADHD' (read: the behaviours considered to be ADHD symptoms, but at lower severity than clinicians have considered diagnosable) show the same genetic causal links—heritability. now that's also curious, no? almost like ADHD is not a discrete distinct genetically caused pathology, but a bunch of traits and behaviours that, like literally every human characteristic, have some genetic as well as environmental influence, and that are artificially grouped together under psychiatric taxa and presumed to be due to an underlying physical (genetic) defect.

indeed, what I'm laying out here is just the basic circularity that underlies all psychiatric diagnosis: we know you are X because you do Y, which you do because you are X, which we know because you showed up to the clinic and told us you do Y. I unpacked this logic in more detail here.

finally, and this bears pulling out from the list because it's important, multiple of these studies are claiming that they have identified general genetic risk factors for a broad variety of psychopathologies (example here). in other words, the claim is not even really that ADHD has specific genetic causes, but that some as-yet-unspecified genetic factor/s are generally responsible for what are diagnosed as mental diseases. how do we know that unspecified higher-order genetic factor exists? well, we don't. but we assume it's there. the same way we did for the 'general intelligence factor,' g, which by the way is entirely racist nonsense.

you may notice that basically all I've said here amounts to accusing psychiatry of failing to meet basic standards of empirical proof generally considered to be load-bearing elements of the 'scientific method.' this is not even really an 'antipsych' argument—it's, at best, a critique of psychiatry as it currently exists, using (in a locally uncritical way!) established standards of scientific discourse. I'm pointing this out both because it's an extremely valuable habit to get into yourself, and because I once again would love it if more people understood that 'antipsych' isn't really a prior theoretical commitment most of us just stumble into. it's a position we actively have to seek out, and often, what prompts us to begin doing that is precisely the experience of noticing problems like the above, and the corresponding utter failure of the psychiatric discipline to rectify such problems without nullifying its own epistemological foundations.

[evidence-based-activism]

Could you do a post on whether sex is binary or not please? Love your blog and appreciate how much effort you put into it!! Huge respect.

Thank you!!

Sex is Binary

Despite efforts to confuse matters, there's one simple fact that underlies the sex binary in animals: anisogamy.

Anisogamy refers to the difference in size of the two types of gametes [1, 2]. Gametes are the sex cells (eggs and sperm), which are combined during sexual reproduction [2]. By definition [3, 4], the females produce the larger gamete (the egg or ova) and males produce the smaller gamete (the sperm).

There are no intermediate gametes; therefore, there are no additional sexes. No human has ever produced both ova and sperm; therefore, every human is either female or male.

Importantly, the sex binary is not equivalent to sexual differentiation or sexual dimorphism. (Although they are strongly correlated.)

Sexual Differentiation

Sexual differentiation refers to the process in which "male and female sexual organs develop from neutral embryonic structures" [5].

Every embryo has both precursor structures: the Müllerian duct, which can develop into the female organs, and the Wolffian duct, which can develop into the male organs. Once sexual differentiation begins, one of these precursor structures will develop into maturity, and the other will atrophy. [5]

In humans, the process of sexual differentiation is controlled by various hormonal secretions by the embryo at specific times during development. These hormonal secretions are determined by the genetic makeup of the fetus. For example, the SRY gene, found on the Y chromosome, regulates the expression of multiple genes which together result in the differentiation of Sertoli cells. In the third month of development, the Sertoli cells secrete Müllerian inhibiting hormone, which initiates the atrophy of the Müllerian duct. [5, 6]

Importantly, therefore, the process of sexual differentiation depends on biological sex. Or, as this article [1] puts it, sexual differentiation is a consequence of biological sex. In a healthy organism, the embryo has the genetic instructions necessary to initiate the process of sexual differentiation that will ultimately result in the production of either ova or sperm (which defines biological sex). This expected capacity or "developmental trajectory" allows us to categorize an organism's sex even in the absence of successful gamete production. Put simply, the organism's biological sex is defined by the gamete they would have produced, had they been capable of producing a gamete.

Disorders/differences of Sex Development (DSD, Intersexism)

The complex process of sexual differentiation can be disturbed at various points, which can result in disorders/differences of sex development (i.e., intersexism). Importantly, however, every embryo starts out with the capacity to produce only one type of gamete. [5]

Further, the development of the ovary is not a "default pathway" [6, 7]. Instead, ovarian development is an active process that necessitates the activity of many factors. The mere absence of complete instructions for male development does not mean a fetus will undergo normative female development.

In other words, each embryo has the genetic instructions necessary to develop the capacity to produce either sperm or ova. However, genetic mutations in many different genes can disrupt this normative development, typically resulting in the absence of any gamete production. These individuals still have a biological sex of either male or female; it is simply determined by which gamete they would have produced had they not had their genetic mutation(s) and instead undergone normal sexual differentiation.

Astonishingly, despite the many possible points of disruption in sexual differentiation, the frequency of genuine intersex conditions is extremely low. Based on the definition of biological sex and our understanding of sexual differentiation, we can describe intersex conditions as conditions in which an individual undergoes some degree of sexual differentiation that is inconsistent with the differentiation for their expected gametic production.

In practical terms, this means that intersex conditions include cases where an individual's chromosomal sex is inconsistent with their phenotype (primary sex characteristics) or they have an ambiguous phenotype. Using this definition, we can estimate that approximately 0.018% of the population has an intersex condition. [8]

And allow me to emphasize again, that these individuals are still either male or female. Their sex can be identified by what type of gamete they would have been capable of producing, had they not had a genetic condition that disrupted their sexual development.

Another way to think of this is that, had these individuals actually been the opposite sex, their genetic mutation would not have impacted their sexual development. For example, people with Complete Androgen Insensitivity Syndrome (CAIS) have a genetic mutation that means their "cells do not respond to testosterone or other androgens", leading to female-typical external genitalia.

This genetic mutation only disrupts the sexual differentiation of biological males. If this person had been biologically female, their sexual differentiation would have proceeded normally. It is possible they may have some other health condition, but they would not have an intersex condition.

Further, the occasional disruption of a biological process does not negate the validity of that process for the species. For example, normative human development results in the development of two (complete) arms and legs. However, some humans are born missing part or all of one or more limbs, which is called limb reduction. In fact, the frequency of this is estimated at 0.05%, which is almost three times greater than intersex conditions. Despite this, we understand that the statement "humans have two arms and two legs" is accurate and does not imply the absence of non-normative phenotypes. [9]

And, in addition to all of this, people with access to modern medicine do not go their "whole life" without knowing they are intersex. Intersex conditions that are not associated with ambiguous genitalia will generally be identified at the onset of puberty or when investigating the cause of infertility. If you were not identified as having an intersex condition at birth, you underwent typical puberty, and you are not having fertility issues, you are not intersex. If you did not undergo typical puberty and/or you are infertile, you may have an intersex condition, but there are also many other more common conditions that cause these issues.

People (now or in the past) who did/do not have access to modern medicine may not have been identified as having an intersex condition if it was not physically obvious at birth/puberty. However, these individuals would present with later health issues, including, but by no means limited to, infertility.

Sexual Dimorphism

Most of the arguments suggesting sex is not binary are based on the assertion that either (1) humans are not sexually dimorphic or that (2) the partial overlap in dimorphic traits suggests a continuum in human sex. Neither of these is true.

First, I've recently made a post on sexual dimorphism, describing a sample of the many ways humans are sexually dimorphic. Hopefully, that is sufficient to refute the first assertion.

Second, I state in that same post that:

It's important to note that it is not necessary for there to be absolutely no overlap between the sexes for any particular characteristic to be considered sexually dimorphic. It is merely necessary for there to be an average difference on the population level. We should also note that, due to the many, many traits in which humans are sexually dimorphic, an individual with an opposite-sex-average trait will typically still be same-sex-typical for the many other traits.

In other words, sexual dimorphism is not equivalent to biological sex, but a consequence of it. Biological sex normally determines sexual differentiation which in turn determines sexually dimorphic traits. However, while there is some degree of overlap in sexual dimorphism (e.g., a man may be as tall as the female-average), there is no overlap in biological sex (i.e., a human cannot produce both eggs and sperm).

(Also, for the Anon who sent a video from an "advanced biologist". See the above for the difference between the sex binary and sexual dimorphism and the relevance of intersexism.)

I hope this helps, Anon!

References under the cut:

Goymann, W., Brumm, H., & Kappeler, P. M. (2023). Biological sex is binary, even though there is a rainbow of sex roles: Denying biological sex is anthropocentric and promotes species chauvinism. Bioessays, 45(2), 2200173.

Sexual Reproduction. Britannica, 15 Feb. 2025, https://www.britannica.com/science/sexual-reproduction.

“Female.” Merriam-Webster.com Dictionary, Merriam-Webster, https://www.merriam-webster.com/dictionary/female.

“Male.” Merriam-Webster.com Dictionary, Merriam-Webster, https://www.merriam-webster.com/dictionary/male.

Sexual Differentiation. Britannica, 3 Dec. 2018, https://www.britannica.com/science/sexual-differentiation.

P A, Aatsha, et al. “Embryology, Sexual Development.” StatPearls, StatPearls Publishing, 2025. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK557601/.

Witchel, S. F. (2018). Disorders of sex development. Best Practice & Research Clinical Obstetrics & Gynaecology, 48, 90-102.

Sax, L. (2002). How common is lntersex? A response to Anne Fausto‐Sterling. Journal of sex research, 39(3), 174-178.

CDC. “Limb Reduction Defects.” Birth Defects, 30 Dec. 2024, https://www.cdc.gov/birth-defects/about/limb-reduction-defects.html.

[greenbirdred]

semi-canon-compliant theoretical nightwing color genetics, woohoo! explanations under the cut!!

"gloss" is the most complicated and distinctive nightwing color modification! once a dragon with "gloss" activated hatches, its teardrop-shaped scales by its eyes will turn silvery to white. a dragon with "gloss" may have it activated later in life, in which case their teardrop-shaped scales may turn silvery but neither mind-reading nor future-sight will activate.

"gloss" is activated in the presence of light. its light detection is synched with a dragon's circadian rhythm, so "gloss" typically only detects light a few hours into night-time. although light-detection is possible while dragonets are in their eggshells, studies suggest that the first few nights after a dragon hatches are the most important for "gloss" activation.

dragons with high "gloss" expression are those who have been born during full moons. the scales by their eyes turn silver; possibly, these scales serve as light-sensing organs, and, upon receiving a large amount of light, they turn silver to reflect more light. high "gloss" dragons tend to have mind-reading or future-seeing abilities—it's thought that the "gloss" gene activates these abilities. visually, high "gloss" dragons tend to have extra layers of keratin on their scales that result in a rich, iridescent appearance.

"gloss" can be activated after hatching, in which case the dragon may gain a lesser version of a high-gloss dragon's iridescent appearance after a molt. a dragon that has not been exposed to moonlight between molts will not have any "gloss" expression.

due to genetic bottlenecks, almost all nightwings living today have the "gloss" gene.

nightwings also have a form of variable piebaldism on their wings! this piebaldism is unstable, and linked to an incompletely dominant allele. the gene expresses as delicate white/silver spotting on the underside of a dragon's wings in its heterozygous form. in its homozygous form, the gene creates large white spots across the dragon's body. dragonets with homozygous spots rarely hatch, and if they do they often die shortly after hatching. this has dramatically limited the nightwing tribe's ability to recover from population bottlenecks.

the last genotype shown here is the sooty complex! this combination of genes results in countershading or differential pigment spread. most nightwings have a few genes of the sooty complex activated, resulting in paler underbellies, darker eye-ridges, etc.

[lonelywretchjervistetch]

Life-List Series #8: MUDU

Common Name: Muscovy Duck Species: Cairina moschata

Description: A dark-colored duck with green and blue wings, and bare skin around the eyes with red wattles Motto: Waddling the line between wild and domestic.

Conservation: Least Common Range: Coasts of Mexico and Central America, extending into South America, down to northern Argentina and Uruguay; introduced to Florida, Texas, and the UK Habitat: Tropical wetlands, coastal lagoons, and lowland marshes; varied for introduced populations, but usually in areas near water

Food: Stems, seeds, grasses, aquatic plants and leaves, small fish and reptiles, invertebrates (especially termites) Breeding Info: Polygamous, although males are territorial and aggressive; single-brooders with mostly maternal care and loose paternal contact after hatching; nest-box and tree-hollow users when nesting, with a clutch of 8 - 15 white eggs that hatch precocial young Sound: ...

Ornithologist's Notes: Is the Muscovy duck actually distributed in Florida? Well, yes and no. Fun fact, first off, there isn't a lot of actual work done on wild Muscovy Duck in their South American range. Most papers you'll see focus on the domesticated variety, which is also the version of the duck introduced outside of its range. But even then, do feral ducks count as a wild species in parts of its range? Maybe. In central and southern Florida, the species has populations in the thousands, distributing far outside of domestic settlements, and enmeshing themselves within wild environments. It's not necessarily invasive, and it fits within existing niches with little overlap, except for one closely-related species I'll get to in the next entry. Also, quick note, those white patches vary wildly in the domestic variety, where they're basically just restricted to those big white wing patches in the wild populations. Is that from introgression from domestic mallards, or a result of hybridization? Maybe. Is that because of the fixing of a deleterious copy of the MYOT and MB gene pairing that controls melanization, alongside differential expression throughout the feathers dependent on some mystery of genomic structure? Very well could be? Are there any papers on that comparison? Not yet. We'll see, though.

Life List Notes: Does this count as a life-list bird? I think so! To be clear, I saw these guys for the first time in central Florida (Orlando), and while they were around a human settlement, they weren't kept in a domestic setting, and seemed like a wild (or feral) flock that had arrived to the water-dominated resort independently, rather than being brought there and fed there. What's more, they weren't heavily domesticated, and at least appeared to be pure Muscovy Duck, rather than hybrids with Mallards (Anas platyrhynchos) or other domesticated duck species. Plus, Florida birders seem to think that these count for life-lists, since they're independently distributed and established. So, does it count? We're gonna say yes! And now, for the next one, we move on to a species that definitely counts for the life-list...even if it is a really common duck to see. Also, we're in ducks now! Excited, I love ducks.

Previous: TRSW

Next: WODU

[born-of-star-flesh]

So as someone who's taken a college biology class with an entire unit dedicated to sex differentiation it's been bugging me immensely to see so many people (mostly on threads) say that "we're all female at conception" There's some truth to female anatomy being the "default baby" because it takes less developmental energy to create/maintain but "we're all female to start" is a way oversimplification of this to the point it's just not true. I'm not claiming to be an expert by any means but I would like to spread the knowledge I do have bc I think it's honestly cool as hell

To start I've seen this talked about a lot in relation to Trump trying to sign an executive order that categorizes people's sex by "the gametes they have at conception" There's so many issues with this. A zygote is not producing gametes at conception, it's a single cell. A zygote carries the genetic coding for which sex you are but genes are not the final determination and only make up part of your sex. For example, you may have an SRY gene which is the catalyst for male development but it may be damaged and not expressed. A person may present entirely as one sex but not be able to produce gametes, Sex isn't just one characteristic.

Once a fetus begins developing its organs it doesn't just start out with female anatomy which can then "become male anatomy if you have the genes for it" We actually start out with undifferentiated gonads (which are still not producing gametes) and two duct systems, one that can become the female reproductive organs and one that can become the male. They're called the Müllerian and Wolffian ducts. (Science illustration so you know I'm not just pulling this out of my ass)

This is where our genes come into play deciding if our gonads become ova or testes and which ducts develop into our reproductive organs. Shout out to all my intersex folks, a lot of intersex conditions become expressed at this stage of development. For example, a person with androgen insensitivity syndrome would have XY chromosomes but would have missing or non-functioning androgen receptors. This means their gonads become testes and the hormone that degrades the Mullerian ducts is released, but their body cannot use any androgens to continue male development. This means without androgens the wolffian ducts also degrade and the person would have external female genitalia and internal testes. My knowledge on the more micro-biology and chemical reactions part of sex determination is more limited so I can't really talk about it in a comprehensive way but I just wanted to share this really cool human fact.

[catboybiologist]

Do you see a future where we can give a trans person a shot and have their body start making the correct sex hormones (eg testes change to make E, or ovaries change to make T)? How far off? What things need to be accomplished to achieve it, and what tools do we already have?

Disclaimer that none of this is gonna be all that scientifically robust, the terms used are gonna be descriptive rather than technical, and that I'm just woke up and these are the ravings of a woman gone mad.

A single shot is ambitious, but I could see a course of several months or a couple years that, after those several months, lasts a lifetime.

How far off? I mean, wildly dependent on funding and focus. Unfortunately, nothing related to trans healthcare is gonna see a serious push I would think. With an actual, serious push, I would give it a few decades of research (if that)(this is blisteringly fast btw) until it's punted over to the FDA. At that point it's outside of my knowledge to know how far things would move forward.

But honestly, it's part politics, part luck of the draw on what people research and push forward. Might happen in our lifetime, but don't hold your breath. Research is grindingly slow.

This is mostly based around the possibility of inducing transdifferentiation. Tldr:

-stem cells are exciting bc they can become any cell type. They haven't "locked in" their cell fate yet.

-most research on cellular differentiation centers around deprogrammed differentiated cells, reverting them to stem cells, and then reprogramming them into something else. The deprogramming is actually well studied (shoutout Yamanaka factors) but I don't see something like this reaching a medicinal, in vivo use soon.

-in extremely rare and induced cases, however, you can force a fully differentiated cell type to become another fully differentiated cell type *without* that intermediate. This is likely way easier to pull off in vivo, even though the initial molecular triggers are much, much rarer and more difficult to study.

Which brings us to the two theoretical dots that we can use here: prostatic metioplasias as a result of testosterone (for transmascs) and the role of DMRT1 for transfemmes.

Broad tldr of each of these points:

-there was a study that studied vaginal lining of transmascs who had been on T for several years and gotten hysterectomies. They found some prostate tissue intercalating the vagina.

-removal of a particular gene (DMRT1) allowed testes to slowly become ovarian tissue and produce estrogens. This gene is responsible for maintaining testes cell fate- keeping the lock, locked.

Neither of these provides a direct basis for actual medication. They show avenues for what will work, however. What's necessary here is to understand the upstream signals that control the expression of genes like DMRT1, which can then be exploited to force expression or stop expression in vivo, in a human.

Basically, the way transdifferentiation would work here is blasting the appropriate cells with enough of these signals, over enough time to ensure that everything actually undergoes TD, to reprogram everything you want to reprogram.

(yes, I know about the crispr transfemme who targeted DMRT1. No, I don't think that's real. I've posted about that before.)

You don't have to bother reading these, but here's the primary sources I'm talking about for anyone interested:

[mychemicalweevil]

You know the TLT brainrot is real when you start TLT-ifying gene names at work. Recently I’ve seen CAV1, NAV3, and CAMK1D pop up when I’m doing differential expression analysis. Why are the best-most-special-cavaliers-ever haunting the narrative of my research and can they stop

[haggishlyhagging]

Natalie Angier's research for her book, Woman: An Intimate Geography, confirms that "in the basic biological sense, the female is the physical prototype for an effective living being. Fetuses are pretty much primed to become female unless the female program is disrupted by gestational exposure to androgens." The Institute of Medicine study describes how our sex begins in the womb, and how the female is the primal matrix:

All human individuals—whether they have an XX, an XY, or an atypical sex chromosome combination—begin development from the same starting point. During early development the gonads of the fetus remain undifferentiated; that is, all fetal genitalia are the same and are phenotypically female. After approximately 6 to 7 weeks of gestation, if the fetus is male, the expression of a gene on the Y chromosome induces changes that result in the development of the testes. In contrast, fetal ovarian secretions are not required for female sex differentiation.

David Crews, of the University of Texas, describes the female as "the ancestral sex, while the male is the derived sex." Angier writes, ". . . eggs are inherently female. So in thinking about mirrors into infinity, the link between mother and daughter, the nesting of eggs within woman within eggs, we can go a step further and see the continuity of the chromosomes. No maleness tints any part of us gals, no, not a molar drop or quantum." There is no maleness in female- XX people, literally, and the culturally ascribed gender categories of masculine and feminine are clearly invented. Thus, females have no "masculine" side, as Freud or Jung would have us believe. This is just patriarchal gender jargon within a patriarchal frame.

If you are female, you have XX chromosomes in every cell. This is reality, a fact, not a belief or opinion, not a theory, not a feeling.

-Ruth Barrett, "Eve Was ‘Framed’" in Female Erasure

[covid-safer-hotties]

Reference archived on our website

Covid causes rapid progression of HPV via immune dysregulation

Abstract COVID-19 is a multisystem disease and cause of a global pandemic. Lately, cases of disease progression of HPV-infected CIN under SARS-CoV-2 infection were reported giving rise to the hypothesis of direct virus-infection induced pro-carcinogenic effect of SARS-CoV-2. We herein present a case of rapid progression from HPV-induced CIN 2 to microinvasive carcinoma within three months under COVID-19 without direct virus infection. Histopathologic evaluation, Fluorescence-in-situ hybridization and qRT-PCR against SARS-CoV-2 RNA as well as gene expression analysis were performed from the available FFPE-tissue and accompanied by an analysis of white blood cell differential. No signs of direct SARS-CoV-2 infection or COVID-19 typical alterations of cervical tissue were found. As expected, p53 decreased in expression with progression of dysplasia, while APOBEC3A and VISTA showed a decrease in expression contrary to observations in dysplasia progression. PD-L1 was expressed consistently or increased slightly but did not show the expected strong induction of expression. DNMT1 showed an increase in expression in CIN III and a slight decrease in carcinoma, while DNMT3a is consistently expressed in CIN II and decreased in carcinoma. Blood tests after COVID-19 showed substantial reduction of lymphocytes, eosinophils, T-cells, and NK-cells. Our results hint at an indirect effect of COVID-19 on the cervical neoplasm. We conclude that the immune system might be preoccupied and exhausted by the concurring COVID-19 disease, leading to less immunological pressure on the HPV-infected cervical dysplasia enabling rapid disease progression. Further, indirect proangiogenic and proinflammatory micromilieu due to the multisystemic effects of COVID-19 might play an additional role

[wanderingskylooker]

Rating of hugs: Big spoon to small spoon (Super 4: Canon)

Twinkle

I think everyone agrees, Twinkle is the biggest spoon of hugs. She hugs every time she can and is a high contact person (fairy), although she respects Gene’s preference to avoid huge amounts of unnecessary contact. She carries Alien in her arms almost all the time, she squeezes him and hugs him.

I had this classmate who got anxious before our presentation and asked me to hold hands and squeeze them hard. I guess it's something my classmate used to do or something to help deal with nerves, but I think that’s something Twinkle would do to release her nervousness, as what she does with Alien. She hugs people using all her strength to calm down.

(Ep: The Furious Elf and The Goose with the Golden Eggs)

Alex

Alex loves hugs, even if he doesn’t hug as much as Twinkle. Hugs are special to him, he is a sweet guy (probably Kenrick taught him that, that old man is a sweetheart). The main difference with Twinkle is that he needs a reason to give a hug, not just completely out of the blue, but to celebrate or show his appreciation over someone else’s actions.

He doesn’t hesitate on receiving a hug, or hesitates, blocks and has the Black Baron calling him “brother-in-law”.

Theory:

When Alex was little he used to hug his father a lot, to the point he was this clingy kid which people were unable to take off until he got distracted with something else. Now he just takes advantage of the smallest reason to hug Kendric but still look like a formal knight.

(Ep: Convoy of Honor and Fairy Snatchers)

Ruby

She is willing to hug, but is much more used to receiving hugs from others. I find probably that Ruby’s resistance to showing affection is her raising as a pirate, not that her father didn’t love her, but the fact that the pirates try to look strong and intimidating, someone whom you don’t want to mess with, and she tried to be much more than a normal pirate to prove she was one of them. At the moment of the show, she doesn’t find the need to be like Sharkbeard and his crew, so if the unstoppable force of Twinkle zooms towards her, Ruby will be the immovable object which will take her in her arms.

To differentiate Ruby and Alex. If hugs were like a post, Alex would be the kind of person who likes what he finds cool, funny, cute, etc, and Ruby would be the kind of person who likes what their friends post and what she actually wants to rewatch on her Like folder.

Twinkle would be the one who likes everything happy, cute, funny, pretty, sweet, with heart, made by a kid who loves the book/series/show/etc …, Alien the one who likes his friend’s posts and Gene who waits for an extremely good masterpiece to deserve his like and rewatch it over and over.

(Ep: Ruby, Queen of the Seas - Part 4 and Saving Pirate Sharkbeard)

Alien

This little fella likes being hugged, even if he needs to put up with the constant squeeze from the characters. His size doesn’t let him pull characters into a hug, but he finds his ways to show affection towards his friends.

(Ep: Worlds Apart and A Mad Mad World)

Gene

Gene just doesn’t find the need to show physical affection, being even less expressive than the average technopolian. He rests his arms slightly crossed, close to his body, formally distant. He is willing to receive hugs, but is quite awkward, more used to using his hands to do small actions.

I said before, in Alex and Gene’s post, that I think Gene is a small details person, for example calling the Chameleon’s fuel, albaperonium, after the fairy he met the first time he arrived at the Enchanted Island, Alba. The same when Ruby transformed back into a human, after being cursed into a dragon, that Gene playfully pulled her hat down, in a way that remains more of Ruby’s mischief than his.

(Ep: All that Glitters and Rage of the Dragon)

[science-sculpt]

Epigenetics: A Journey Through Inheritance Beyond Genes

For centuries, scientists have been fascinated by the mysteries of heredity and how traits are passed down from generation to generation. DNA, the molecule that stores our genetic code, was once thought to be the sole determinant of our characteristics. However, a new frontier in biology, revealing a captivating layer of complexity beyond the DNA sequence itself: Epigenetics.

What is Epigenetics?

The term "epigenetics" was first coined in the 1940s by British biologist Conrad Waddington, but it wasn't until the late 20th century that its significance truly blossomed. Epigenetics, literally meaning "above genetics," refers to the study of heritable changes in gene expression that occur without alterations to the DNA sequence itself. Imagine DNA as the musical score, but epigenetics are the conductor and musicians who determine how the music is played. Through chemical modifications and adjustments to the proteins around DNA, epigenetics dictates which genes are turned on or off, influencing how cells function and ultimately shaping our health, development, and even behavior. Think of your DNA as the hardware: it contains the basic instructions for building and running your body. But epigenetics acts like the software, fine-tuning those instructions and determining which genes get turned on or off at specific times and in specific cells. These modifications, like chemical tags or changes in the packaging of DNA, don't alter the underlying code itself, but they can have a profound impact on how it's read and interpreted.

The Key Players:

DNA methylation: This process involves adding a methyl group to DNA, essentially silencing the gene it's attached to. Imagine it like putting a dimmer switch on a light bulb.

Histone modifications: Histones are proteins that package DNA, and changes in their structure can make genes more or less accessible to the cellular machinery needed for expression. Think of it like adjusting the curtains around a window - open wide for full light, slightly closed for filtered light.

Non-coding RNAs: These are molecules that don't code for proteins but can regulate gene expression in various ways. They're like the backstage crew in a play, ensuring everything runs smoothly.

The Power of Epigenetic Regulation

Epigenetic regulation plays a crucial role in various biological processes, including:

Development: During embryonic development, different cell types emerge from the same DNA blueprint by activating or silencing specific gene sets through epigenetic modifications.

Cellular differentiation: Specialized cells like muscle or nerve cells have unique functions due to differences in their active genes, controlled by epigenetic mechanisms.

Learning and memory: Epigenetic changes in brain cells are thought to be essential for learning and forming memories.

Aging: As we age, our epigenome accumulates changes that can contribute to age-related decline and disease.

Environmental influences: Diet, exercise, stress, and exposure to toxins can leave epigenetic marks on our genes, potentially impacting our health and even the health of future generations.

Epigenetics reminds us that we are not simply products of our genes. Our environment, choices, and experiences leave their mark, shaping who we are and potentially influencing our children's health. This deeper understanding of ourselves opens doors for self-awareness, empowerment, and potentially reshaping our narratives – not just as individuals, but as a species with the potential to leave a healthier legacy for generations to come.

[o-craven-canto]

The processes that can turn an aggregate of cells into a complex organism. ADH: cell adhesion. APO: apoptosis, or selective cell death. ASM: asymmetrical morphogenesis. DAD: differential cell adhesion, sorting cells by type. ECM: secretion of extracellular material. LAT: lateral inhibition, a switch that can turn a cell into two different states. MIT: mitogenesis, or localized cell division. MOR: diffusion of a morphogenic signal. OSC: timed osclllation between different states. POL: polarization, or differential properties at different ends of a cell. TUR: Turing reaction-diffusion pattern. (pic: Newman & Bhat)

It's all well and good to say that DNA contains the instructions to produce an organism, but all DNA can do is induce the secretion of chemicals. There are no printed instructions or little foremen supervising the growth of an embryo. So how does secreting chemicals in a clump of identical cells end up producing something as complex as an animal?

Here's some tricks.

Differential adhesion. The cells of all animals have surface proteins called cadherins that bind each other into solid tissues. If all cells were uniformly covered in cadherins, they would form homogeneous spherical lumps; but if some cells are covered more or less sparsely than the others, then they will spontaneously sort by cadherin density, forming clumps and layers much like the spontaneous sorting of water and oil. If some surfaces are not adhesive at all, those will find themselves surrounding cavities. (pic: Gilbert & Barresi)

Lateral inhibition. The Notch protein forms a trans-membrane complex; when the external portion receives a signal from the environment, the internal portion breaks off and enters the cell nucleus to activate the expression of otherwise repressed genes. Thus, the Notch system works as a switch between two different states of a cell depending on whether or not it receives a particular signal. This is called "lateral inhibition" because it makes neighbor cells, such as neurons and glia in the brain, develop into complementary forms repressing each other's unnecessary genes. (pic: Audrey Effenberger, Wiki)

Cell polarization. "Wnt" is the name of a family of secreted signal proteins that have a multitude of functions. Among this is establishing cell polarity: through a cascade of signals, it can cause the cell's cytoskeleton -- its internal scaffolding -- to rearrange itself into an asymmetrical shape (... I think. This part of the process isn't fully clear to me), which leads to further differentiation. If the polarity involves different types or densities of adhesion proteins, then differential adhesion will sort polarized cells into distinct layers or hollow sacs and tubes -- hence, organs and body cavities. Cell polarization also leads to the establishment of the head-tail and back-belly body axes. (pic: Gilbert & Barresi)

Morphogenic gradients. When a cell or group of cells start secreting a diffusing chemical, this will naturally form a gradient with its concentration fading away with distance. This can direct differential development of cells over the organism body. Even if the chemical gradient is smooth, the morphological one doesn't need to be: cells can have different thresholds that will cause them to take one or another form. So there will be different discrete types of cells, each developing at a fixed range of distances from the source of the gradient. For example, in vertebrates, the protein Shh in the notochord induces the formation of motor neurons in the ventral side of the neural tube, which is closest. (pic: Gilbert & Barresi)

Asymmetrical morphogenesis. But then how do we end up with asymmetrical morphogenesis, for example our heart growing more on the left than on the right side? Morphogens don't have to spread only by themselves: in vertebrates, the morphogenic protein Nodal is systematically pushed to the left by beating cilia. Malformations in cilia can result into situs inversus, the development of organs in a position that mirrors the usual one. In addition (see "reaction-diffusion" below), Nodal induces the secretion of the protein Lefty2 which in turn inhibits Nodal and spreads faster, resulting into a side of the body where Nodal cannot accumulate. (pic: Green & Sharpe)

Chemical oscillation. If gene-activating factors inhibit their own synthesis, then they will come and go in regular waves, growing when they are few and decaying when they are many. This gives cells their own internal clock, which for example allows a cell to replicate at regular intervals. In multicellular organisms, the oscillation occurs in space as well as in time, as growth signals are released in waves. So they determine the formation of regular segments: for example, our vertebrae. (pic: Müller et al.)

Extracellular matrix secretion. While cells in epithelial tissues (like the outer layers of skin, or the lining of body cavities) stick closely to each other, those in connective tissues (like the inner pulp of skin, cartilage, or fat) are sunken in a matrix of various composition, but which usually contains elastic fibers of collagen. When a cell develops into a fibroblast, it starts secreting around itself the component of extracellular matrix with various mechanical properties, affecting the shape and structure of the body (especially when the cell is polarized). Even bone is simply a connective tissue whose matrix in rich in calcium phosphate mineral.

Turing patterns (reaction-diffusion). A chemical produced by a cell activates both itself and its own inhibitor. Activation is powerful but short-ranged; inhibition is weaker but spreads farther. Once a cell has produced the chemical past a critical threshold, its keeps reinforcing its own production, but also inhibits its neighbor from doing the same. At a greater distance, however, another cell or group of cells could also start the synthesis on their own. Depending on the range and power of activation and inhibition, this produces all sorts of patterns of activation: spots, stripes, waves, grids, rings. (pic: Green & Sharpe; Metz &al)

Apoptosis. Cells that receive a certain signal die, and their matter is recycled. If the signal of death is distributed according to Turing patterns, then living tissue can be cut and molded in very precise ways. For example, cells in the developing limb-bud of a vertebrate die in waves leaving behind parallel cylinders: the beginning of fingers.

Multiple mechanisms coming together to make vertebrate limbs: a morphogenic gradient distinguishes base and tip of a forming limb; reaction-diffusion creates a Turing pattern (diverging waves) that determines where finger bones will develop; and finally apoptosis cuts away the intermediate tissue. (pic: Green & Sharpe)

SOURCES

Gilbert & Barresi (2016), Developmental Biology Green & Sharpe (2015), Positional information and reaction-diffusion: two big ideas in developmental biology combine Newman & Bhat (2009), Dynamical patterning modules: a "pattern language" for development and evolution of multicellular form