CrateDane

CrateDane t1_iswoeir wrote

> When you have an acute infection, you can deplete things like DCs and other phagocytes briefly

That is not really true, GM-CSF for example actually causes proliferation so you have more phagocytic cells available.

It's true that it isn't super-immunity though, and secondary infections can happen in some cases. But generally, an acute infection that the immune system can handle is something that will briefly boost your resistance to other infections. Especially infections of the same type and even more so in the same area - see eg. viral interference.

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CrateDane t1_isu6m6d wrote

That is generally not correct. The first infection will cause release of PAMP and DAMPs which trigger an induced innate immune response, which will tend to limit the second infection. For example, interleukin 12 will activate natural killer cells, to better kill virus-infected cells. The response also acts on fat and muscle to mobilize nutrients for use (eg. to sustain the required energy for a higher body temperature - which is incidentally another response that limits the growth of some pathogens).

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CrateDane t1_isepor7 wrote

>Without binocular sight it is impossible to get distance to and size of objects.

That is not correct. You only lose the binocular parallax information, but the brain still receives and processes many other cues. Motion parallax is one example that works fairly similarly to binocular parallax, just with one eye being in different positions over time rather than two eyes being in different positions simultaneously.

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CrateDane t1_irnv403 wrote

> > > > > Finally, chromosomal structure and epigenetic modifications haven't been mentioned here. CRISPR/Cas9 gene editing doesn't provide the tools to restructure chromosomes, either in terms of the grouping of DNA into chromosomes or the packing of DNA into chromatin, nor does any other technology I'm aware of. I'm sure some researchers have been able to induce particular chromatin modifications, but much of how epigenetic regulation works remains unknown.

dCas9 (or other Cas proteins) can be fused to a variety of chromatin modifying factors, so epigenetic editing is entirely possible. But good luck doing that across the entire genome in a single cell.

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CrateDane t1_irbbmet wrote

> > > Mammalian Proteins are Glycosylated - this process is inherently heterogeneous. Most of proteins that are produced in humans and other mammals are covered with glycans (sugars) of varying length (1-20 monomer sugars).

Extracellular ones yes, but it's less common for cytoplasmic proteins.

On the other hand, you have a crapton of other modifications that are common on intracellular proteins. Phosphorylation, methylation, acetylation, acylations in general, SUMOylation, ubiquitination, neddylation, succinylation and so on and on.

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CrateDane t1_irb9tcb wrote

> > > > > Folding of proteins and post transcription modifications are significant enough and different that for instance insulin can only be made in eukaryotes if you want it to really function well in human systems.

Well, there are ways around it. Some companies produce insulin in bacteria, while others produce it in yeast. It's a tradeoff since yeast is better at making it correctly in the first place, but is otherwise a less efficient and more complicated expression system than bacteria.

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CrateDane t1_ir6tx4r wrote

Nowadays, CRISPR-Cas is one of the easiest tools to use to knock out a gene. You deliver Cas9 (or Cas12a etc) plus sgRNA to cells, which causes a break to be made in a very specific spot. Then the cell tries to repair the break, usually via a messy pathway called NHEJ which often leaves the gene functionally inactive.

If you can live with just partially shutting off the gene, RNA interference is also very popular and can be very quick and easy to do.

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CrateDane t1_ir1k7n7 wrote

> > > > > Now assume you find a gene that seems highly conserved amongst a vast amount of species. But you have zero clue what it does. And you want to know. Usually, first step is to just delete it in a model and see what happens. Nothing happens? Okay, over express it. Nothing happens? Okay, try to see what the produced protein (theoretically or experimentally known) is similar to in sequence and structure (domains). That might give you a vague hint at what it might be involved it. If you have that hint, perhaps now you can delete it and challenge your cells or animal model with a stressor relevant to that hint. For example, perhaps you find the protein is similar to those involved in tight junctions, so now you can try to challenge your model with different deficiencies in whatever ions or other things to see if the mutated group is more severely affected.

Or you could screen for synthetic lethality / synthetic phenotypic alteration. It's not uncommon for there to be other genes that can compensate for the loss of your gene of interest; but then a double or triple mutant will usually have the relevant altered phenotype.

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