Fatal Familial Insomnia (FFI) is a genetic disorder caused by a mutation in the PRNP gene. The PRNP gene codes for the prion protein, thought to be involved in copper signaling and cell adhesion. For the mutation itself, at position 178, asparagine (N) replaces the wild type aspartic acid (D); D178N is the correct notation. However, what determines if someone shows the pathology of FFI or familial Cruetzfeldt-Jakob (fCJD), depends on another position on the mRNA that’s translated. The D178N mutation must be coupled with a methionine at position 129; this site is the valine/methionine polymorphism site.

Homozygotes at codon 129 show a shorter disease duration, more severe insomnia, and the disease is mostly restricted to the thalamus.

Heterozygous at codon 129 show a longer disease course and other symptoms, such as ataxia and dysarthria; the disease is not restricted to the thalamus, and can spread to other parts of the brain, such as the cerebral cortex.

Hypertumors are tumors that invade and disrupt the growth of an already existing tumor. Hypertumors essentially “steal” nutrients from the “host tumors.” The host tumor and hypertumors essentially compete for resources.

See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060950/

About the central dogma of molecular biology, it doesn’t necessarily specify locations. Prokaryotes lack a nucleus and instead have a nucleoid, yet still follow the general basis of the central dogma. The central dogma moreso specifies products, DNA to RNA to protein.

First, DNA/RNA can actually enter the nucleus. Nuclear import is controlled by special amino acid sequences known as nuclear localization sequences. This, along with importin (transport protein) allows macromolecules to enter the nucleus through the nuclear pore complexes. tRNA, for example, are imported back into the nucleus, which has been shown in yeast. Plasmid DNA import has also been demonstrated.

When a cell divides, it’s nuclear envelope breaks down, so the mitotic spindle apparatus can invade and attach to the chromosomes. Then, the viral nucleic acids can interact with the hosts’. HIV, howeve, can enter the nucleus even if the cell isn’t dividing. It’s thought that the HIV genome uses the host’s cellular machinery to move into the nucleus. The HIV cDNA (result of reverse transcription) is coated with a myriad of proteins which allow it to cross into the nucleus.

Figure 1 in this paper should give you a good visualization: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325773/

TL;DR: HIV sneaky. :( The idea of the central dogma of biology has some loopholes, with reverse transcription, and direct translation from DNA to protein. Always* exceptions to rules, that’s what makes science so amazing.

Splice-switching antisense oligonucleotide (SSOs) technology utilize modified RNA to disrupt pre-mRNA splicing. When mRNA is first transcribed from DNA, it contains regions known as introns, which do not contribute to the final protein product. These introns are removed, and the regions that do contribute to the finalized protein product, exons, are ligated together. Aberrations in pre-mRNA splicing contribute to a myriad of human diseases, such as Duchenne Muscular Dystrophy. Cryptic splice sites are when a pre-mRNA has incorrect splicing sequences in a pre-mRNA. This can be a result of a single point mutation, causing a deletion in the entire pre-mRNA, leading to a truncated protein.

SSOs are engineered to bind to these faulty pre-mRNAs, and disrupt the intron splicing machinery from binding and creating an aberrant transcript. They can modulate splicing patterns to create an mRNA that produces a “lesser of two evils (less worse)” protein.

Of course, CRISPR is likely more suited to alter single nucleotide substitution mutations, but that’s an application of RNA-based technologies that isn’t talked about as much. Splicing can be a big problem, especially with cryptic splice sites.

Proteasomes are complexes that degrade proteins rather than nucleic acids. For cleavage of nucleic acids, you’d want to look at endonuclease or exonucleases, restriction enzymes. Proteasomes typically are involved in degrading misfolded proteins (look into prions!), or proteins that are no longer needed in the cell. Just a minor correction, hope it helped. :3

There are other gene editing systems out there, such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENS.) ZFNs are nucleases fused to a zinc finger DNA binding domain. You can engineer ZFNs to target a specific nucleic acid, just as CRISPR-Cas9 does. However, CRISPR-Cas9 systems are revered for their simplicity, essentially just needing the DNA sequence you want to target. TALENs functions like ZFNs, a nuclease bound to a TAL (transcription activator-like effector), which recognizes a specific DNA site. There are other gene editing tools, you can see that among Cas9, ZFNs, and TALENs, the structure/function of the tool is conserved.

Cancer cells and cells infected with HIV have shown to respond promisingly to CRISPR-Cas9 treatment. Ironically, CRISPR systems originated in prokaryotic species, as a defense against mobile genetic elements (MGEs), like viruses or bacteriophages. But CRISPR-Cas9 is being studied as a defense against viral infections, targeting the viral nucleic acids at different stages.

It’s not necessarily always a result of the virus itself, but things like the Zika virus can influence testicular tissue and germ cells, as ZIKV replicates in those cells: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159993/

But as for a minor case of influenza or the common cold, I would be wary about the rising temperature in the body due to the immune response. That can impact sperm production and integrity.

I believe ~10-15% of genes on the Barr Body escape X-inactivation. This means that in the X0 genotype, you are missing those 10-15% genes and their expression, which is an issue. It’s the opposite in Klinefelter’s, XXY genotype. Because you have two X chromosomes, one undergoes X-inactivation which is to be expected in the XX genotype. But you have 10-15% MORE due to that Barr Body, since in a normal XY genotype, you’re not supposed to have that extra X.

Think about it, we inhale O2 to be that terminal electron acceptor. We expel CO2 as a waste product of cellular respiration. So indirectly, we expel CO2 as waste from what we breathe, since we need O2 for cellular respiration. Also, what they may be referring to is gas exchange.

Oh wow, that’s really interesting. Do you have any readings about that?

All translation begins in cytosol, by a cytosolic (free) ribosome. Remember, the rough endoplasmic reticulum is studded with ribosomes. A protein has a specific amino acid sequence that signals the ribosome where that protein needs to move. If that signal is reached during translation of the protein, this is called co-translational protein translocation (a mouthful, I know.) This typically pertains to proteins that are involved in cell membrane structure or proteins that need to be secreted. The ribosomes move to the RER with the incomplete protein, and feed it into the RER.

For proteins that stay inside the cell, they are shuttled to where they need to go because of the recognition of their targeting sequence. This is post-translational translocation. Specifically, for nuclear import (which is very selective), a special tag called a nuclear localization signal (NLS) is attached to the protein so it can pass through the nuclear pores.

Here’s a nice paper on this: https://www.ncbi.nlm.nih.gov/books/NBK26932/ “…histones, DNA and RNA polymerases, gene regulatory proteins, and RNA-processing proteins—are selectively imported into the nuclear compartment from the cytosol, where they are made.”

I’d love to answer any questions you may have! EDITS: Spelling, structure of paragraphs