Why do you think

Calilasseia · May 31, 2023, 12:02pm

Oh look, the in tray is once again filled with the usual bullshit and lies to be shredded. I’m going to enjoy this.

Let’s take a look at this shall we?

I’ll start by mentioning that I’ve a little surprise to unveil while I feed this latest steamng pile into the composting machine, but I’ll ask the regulars to be patient - it’’ be worth the wait.

Once again, do learn the elementary distinctions at work here. Namely, the distinction between individual human beings deciding for themselves what “meaning” or “purpose” their lives may have, and the blind assertion that “meaning” and “purpose” are purportedly an intrinsic part of the fabric of the universe. The evidence for the former is overwhelming; the evidence for the latter is zero. You keep pushing this bullshit conflation of the two, for the usual dishonest apologetic purposes, and those of us who paid attention in class can see through your tissue of lies with ease.

See above. Your conflation of two entirely different assertions about “meaning” or “purpose” is not only fatuously wrong, but duplicitous.

Ahem, the chemicals in my brin facilitate my ability to engage in data processing. Which is basically what thought is from an abstract standpoint.

Furthermore, scientists have demonstrated for decades, that we don’t need any magic “god sauce” to perform data procesing tasks, including advanced ones, because computers have been performing these tasks for that period of time. Indeed, no less a person that Alan Turing, in his seminal paper On Computable Numbers taught us this lesson, when he invented the Turing machine. Indeed, in that paper, he demonstrated that there exists a universal Turing machine, that can perform any task performed by any “lesser” Turing machine dedicated to one task. Its the reason modern computers are so powerful - they are direct physical embodiments of that idea.

Just becausse you’re too stupid to understand how testable natural processes can achieve the end result, doesn’t mean we need a superfluous and imaginary cartoon magic man from a goat herder mythology to explain that end result. Indeed, neurons have been demonstrated to perform the same functions as logic gates. But there’s an even bigger surprise waiting in the wings on this issue, which I’ll come to in due course.

The only one lying here is you, mythology fanboy.

Ah, more duplicitous apologetics.

Once again, we have evidence that human beings make the requisite decisions about what “meaning” or “purpose” their lives have. The reason this process comes under the heading of “subjective”, is because each human being makes a different decision in this regard. That they make the decision is an objective fact; what decision they make, being their own unique choice, is what falls under the heading of “subjective”.

Do you really need baby steps this simple?

Obviously, you and all the other mythology fanboys.

Complete and utter bollocks. The Genesis creation myth never happened. The fantasy “global flood” never happened. Exodus never happened.

Plus, your sad little goat herder mythology is littered with fatuous and absurd assertions about the natural world, that no genuinely existing god type entity would allow itself to be associated with. Such as that garbage about genetics being purportedly controlled by coloured sticks.

Bullshit. “Intelligent design” is a deceitful attempt to push creationism into science classes where it doesn’t belong, by sneaking in wearing a stolen lab coat.

Indeed, as an invertebrate zoologist, I’m aware of a hilarious example that blows this drivel out of the water with a nuclear depth charge. Courtesy of the fact that there exist Carabid beetles with fully functional wings, but which will never be able to use them, because their elytra are fused shut. This is practically a canonical example of stupid design.

But of course we have the evidence from the IDists themselves, that ID is basically an act of deceit, courtesy of the Wedge Strategy document.

As usual, you’re talking out of your arse.

Poppycock. Those 100,000 plus peer reviewed scientific papers from the prebiotic chemistry literature, destroy this feculent assertion wholesale.

Oh look, the mythology fanboy has resurrected Canard #10 from my Grand List of Creationist Canards. Ha ha ha ha ha ha.

Read that list, and while doing so, learn what scientists actually mean when they use the word “random”. Hint: the rigorous meaning thereof bears NO relation to your creationist canard version.

Now let’s move on to the rest of the bullshit …

Sit tight, Looby Loo, you’re in for a surprise.

Those lies of yours keep coming thick and fast. Oh wait, hwo many peer reviewed scientific papers have you presented to support any of your assertions? None.

And now, boys and girls, it’s time for a special surprise.

I was recently pointed to this scientific paper:

The Neuronal Gene Arc Encodes A Repurposed Retrotransposon Gag Protein That Mediates Intercellular RNA Transfer by Elissa D. Pastuzyn, Cameron E. Day, Rachel B. Kearns, Madeleine Kyrke-Smith, Andrew V. Taibi, John McCormick, Nathan Yoder, David M. Belnap, Simon Erlendsson, Dustin R. Morado, John A.G. Briggs, Cédric Feschotte, and Jason D. Shepherd, Cell, 172: 275-288 (11th January 2018) [Full paper downloadable from here]

For those who want to gain some background before I delve into this paper, a non-technical account can be read here.

From that paper:

Pastuzyn et al (2018):

SUMMARY

The neuronal gene Arc is essential for long-lasting information storage in the mammalian brain, mediates various forms of synaptic plasticity, and has been implicated in neurodevelopmental disorders. However, little is known about Arc’s molecular function and evolutionary origins. [b]Here, we show that Arc self-assembles into virus-like capsids that encapsulate RNA. Endogenous Arc protein is released from neurons in extracellular vesicles that mediate the transfer of Arc mRNA into new target cells, where it can undergo activity-dependent translation. Purified Arc capsids are endocytosed and are able to transfer Arc mRNA into the cytoplasm of neurons. These results show that Arc exhibits similar molecular properties to retroviral Gag proteins. Evolutionary analysis indicates that Arc is derived from a vertebrate lineage of Ty3/gypsy retrotransposons, which are also ancestors to retroviruses. These findings suggest that Gag retroelements have been repurposed during evolution to mediate intercellular communication in the nervous system.

Basically, what this paper is telling us, is that a central part of brain chemistry responsible for the connectivity of neurons, and transmission of persistent memory data between neurons, began life as a retrovial insertion in the deep evolutionary past of vertebrates.

The authors open with:

Pastuzyn et al (2018):

INTRODUCTION

Brains have evolved to process and store information from the outside world through synaptic connections between interconnected networks of neurons. Despite the fundamental importance of information storage in the brain, we still lack a detailed molecular and cellular understanding of the processes involved and their evolutionary origins. Eukaryotic genomes are littered with DNA of viral or transposon origin, which compose about half of most mammalian genomes (Smit, 1999). A growing body of evidence indicates the sequences encoded by these elements can provide raw material for the emergence of new functions and regulatory elements (Chuong et al., 2017). In vertebrates, these include dozens of protein-coding genes derived from sequences previously encoded by transposons (Feschotte and Pritham, 2007) or retroviruses (Kaneko-Ishino and Ishino, 2012). Interestingly, many of these transposon-derived genes are expressed in the brain, but their molecular functions remain to be elucidated.

The neuronal gene Arc contains structural elements foundwithin viral Group-specific antigen (Gag) polyproteins that may have originated from the Ty3/gypsy retrotransposon family (Campillos et al., 2006; Shepherd, 2017; Zhang et al., 2015), although the role these Gag elements play in Arc function has not been explored. Arc is a master regulator of synaptic plasticity in mammals and is required for protein synthesis-dependent forms of long-term potentiation (LTP) and depression (LTD) (Bramham et al., 2010; Shepherd and Bear, 2011). Arc can regulate synaptic plasticity through the trafficking of AMPA-type glutamate receptors (AMPARs) via the endocytic machinery (Chowdhury et al., 2006). This endocytic pathway maintains levels of surface AMPARs in response to chronic changes in neuronal activity through synaptic scaling, thus contributing to neuronal homeostasis (Shepherd et al., 2006). Arc’s expression in the brain is highly dynamic; its transcription is tightly coupled to encoding of information in neuronal circuits in vivo (Guzowski et al., 1999). Arc mRNA is transported to dendrites and becomes enriched at sites of local synaptic activity where it is locally translated into protein (Steward et al., 1998; Waung et al., 2008). Intriguingly, aspects of Arc mRNA regulation resemble some viral RNAs, as Arc contains an internal ribosomal entry site (IRES) that allows cap-independent translation (Pinkstaff et al., 2001). Arc is required in vivo to transduce experience into long-lasting changes in visual cortex plasticity (McCurry et al., 2010) and for long-term memory (Guzowski et al., 2000; Plath et al., 2006). In addition, Arc has been implicated in various neurological disorders that include Alzheimer’s disease (AD) (Wu et al., 2011), neurodevelopmental disorders, such as Angelman (Greer et al., 2010; Pastuzyn and Shepherd, 2017) and Fragile X syndrome (Park et al., 2008), and schizophrenia (Fromer et al., 2014; Manago` et al., 2016; Purcell et al., 2014). Thus, precise regulation of Arc expression and activity in the nervous system seems essential for normal cognition.

Despite its importance, little is known about Arc protein biochemistry and molecular function. Here, we uncover a potential role for Arc in mediating intercellular communication via extracellular vesicles (EVs). Synaptic communication is modulated by many other communication pathways that include glia-neuron interactions, and emerging evidence suggests that EVs mediate intercellular signaling in the nervous system (Budnik et al., 2016; Zappulli et al., 2016). EVs can be broadly divided into two groups, microvesicles and exosomes, which are defined both by size and subcellular origin. Microvesicles pinch off from the plasma membrane directly and are usually 100– 300 nm in diameter, whereas exosomes are derived from intraluminal vesicles that originate from multivesicular bodies (MVBs) and are usually <100 nm in size. EVs can transport cargo that do not readily cross the plasma membrane, such as membrane proteins and various forms of RNA. The observation that EVs can function in the intercellular transport of these molecules within the nervous system opens an entirely new perspective on intercellular communication in the brain.

Here, we find that Arc protein self-assembles into oligomers that resemble virus capsids and exhibit several other biochemical properties seen in retroviral Gag proteins such as RNA binding. Moreover, Arc is released from neurons in EVs and is able to transfer its own mRNA into neurons. The Drosophila Arc homolog, dArc1, also forms capsids and mediates intercellular transfer of its own mRNA at the fly neuromuscular junction (Ashley et al., 2018, this issue of Cell), despite originating from a distinct retrotransposon lineage. These data suggest that co-option of retroviral-like Gag elements may have provided an evolutionary pathway for novel mechanisms that mediate intercellular signaling and have been intricately involved in the evolution of synaptic plasticity and animal cognition.

I’ll let everyone read the rest of the paper, as it’s fascinating enough not to let me spoil the juicy parts for you, but the practical upshot of the above work is:

Pastuzyn et al (2018):

DISCUSSION

Here, we show that mammalian Arc protein exhibits many hallmarks of Gag proteins encoded by retroviruses and retrotransposons: self-assembly into capsids, RNA encapsulation, release in EVs, and intercellular transmission of RNA. These data suggest that Arc can mediate intercellular trafficking of mRNA via Arc EVs (which we term ‘‘ACBARs’’ for ‘‘Arc Capsids Bearing Any RNA’’), revealing a novel molecular mechanism by which genetic information may be transferred between neurons.

Arc Functions as a Repurposed Gag Protein

Our data show a remarkable conservation of viral Gag properties in Arc. Since Arc shows structural homology to the Gag CA domain (Zhang et al., 2015), the capability of self-assembly into oligomeric capsids is perhaps not too surprising. However, Arc seems to retain other important biochemical properties of Gag that are not intuitive from its sequence. Despite lacking clear zinc-finger RNA binding domains such as in HIV Gag, Arc encapsulates RNA, and RNA binding seems critical for capsid formation. This is reminiscent of Foamy Virus Gags, which have evolved different RNA-binding motifs to HIV Gag (Hamann and Lindemann, 2016) and also structurally resemble Arc (Taylor et al., 2017). HIV Gag-RNA interactions are complex and involve multiple components of Gag, including the MA domain, and are regulated by host cellular factors (Mailler et al., 2016). Gag MARNA interactions are also critical for virus particle formation at membranes (Kutluay et al., 2014). Moreover, if viral RNA is not present, Gag encapsulates host RNA, and any single-stranded nucleic acid longer than ~20–30 nt can support capsid assembly (Campbell and Rein, 1999), indicating a general propensity to bind abundant RNA. Indeed, precisely how viral RNA is preferentially packaged into Gag capsids in cells remains an intensive area of investigation (Comas-Garcia et al., 2016).

After a few paragraphs covering that Arc reveals a new and hitherto unsuspected signalling pathway in neurons at the molecular level, the authors continue with:

Pastuzyn et al (2018):

Evolution of Synaptic Plasticity and Cognition

Ty3/gypsy retrotransposons are ancient mobile elements that are widely distributed and often abundant in eukaryotic genomes and are considered ancestral to modern retroviruses (Malik et al., 2000). There is evidence that coding sequences derived from Ty3/gypsy and other retroviral-like elements have been repurposed for cellular functions repeatedly during evolution (Feschotte and Gilbert, 2012). For instance, multiple envelope genes of retroviral origins have been co-opted during mammalian evolution to promote cell-cell fusion and syncytiotrophoblast formation in the developing placenta (Cornelis et al., 2015). There are more than one hundred Gag-derived genes in the human genome alone (Campillos et al., 2006), and genetic KOs of their murine orthologs have revealed that some, like Arc, are essential for cognition (Irie et al., 2015). However, the molecular function of these Gag-derived proteins has been poorly characterized, and whether they were co-opted to serve similar cellular processes remains an open question. This study and the accompanying article from Ashley et al. (2018) now reveal that two distantly related Gag-derived genes have been independently co-opted in fly and tetrapod ancestors to participate in a similar process of EV-dependent intercellular trafficking of RNA in the nervous system. Given the plethora of retroelements populating eukaryotic genomes, we speculate that many other Gag proteins have been repurposed for cellular processes that await discovery in a variety of organisms.

Let me encapsulate that for you succinctly. An ancient retroviral insertion into early vertebrate genomes 400 million years ago, was co-opted by those vertebrates for signal transmission between neurons, and as a corollary, forms part of the molecular basis for our cognition.

Our ability to think and reason comes not from a cartoon magic man from a goat herder mythology, but from a 400 million year old viral incursion into Sarcopterygian genomes. Which we inherited after lots of rounds of evolutionary modulation and transformation.

Thought that would make a few eyebrows raise …