Monday, May 04, 2020

GETTIN' CLOSER

In the “old days” when one went to the doc, one supplied a “pee” sample for analysis.  The office had a bathroom with a little door-through so the container could be passed through to the nurse or lab tech without embarrassing everyone.  They also used to take temperatures.  

Now we begin to realize that checking urine for sloughed off epithelial cells is an important clue to a corona virus that attacks the epithelial linings of the body, and a fever is one of the first signs that the body is fighting something.

Epithelial Polarity
Karen L. Edelblum, Jerrold R. Turner, in Mucosal Immunology (Fourth Edition), 2015

Epithelial cells are uniquely positioned at the interface where self and non-self meets. In the lung, epithelial cells must separate the airways, and potential harmful materials within them, from the blood stream while allowing the free diffusion of oxygen and carbon dioxide. The intestine is an even more challenging environment, for in addition to preventing luminal toxins, microbiota, and microbial products from accessing deeper tissues, the intestinal epithelium must support vectorial, or directional, transport of nutrients, ions, and water. The development of epithelial polarity requires accurate delivery of specific transport proteins to either the apical surface (i.e., the surface in contact with the lumen) or the basolateral surface, which interfaces with the interstitium. These transporters are not only critical for promoting active transcellular transport, but also establish transepithelial gradients that provide the driving force for passive paracellular transport.’’

EXPERIENCE REMARKS

The first time i saw a body ‘parted out’ — that is, eviscerated and skinned — i was impressed that each organ and those that were related were wrapped in a silvery thin tissue almost like Saran-wrap.  

We don’t normally see epithelial cells except as our outer skins but we read about ‘’pericardial infection’’ filling the bag around the heart with fluid to the point of stopping the heart.   So in terms of the tension between the cross, the Procrustean rational logic of the crux, versus the observing, exploring, and saving of the bundle as in the feminist and indigenous basic metaphor, epithelia may be at the heart of things.  The basic bodily crux demonstration is the skeleton, our symbol of death, and yet its structure defines us. It is not invulnerable.  The bundle might be the heart but it could also be guts.  Certainly it’s more visceral than structural.

MORE TECH

‘’Epithelial cells are firmly joined together by adhesion specializations. These special structures serve to anchor the cytoskeleton of each epithelial cell to its neighbours and to anchor the epithelium to underlying or surrounding extracellular matrix materials.

Epithelial cells are further specialized by modifications of their surfaces to fulfil their specific role, which may be absorption or secretion or to act as a barrier.’’

Epithelial tissues also operate as filters or for diffusion of fluids like milk.  They can regulate, which means keeping various elements within the bounds of homeostasis.  Epithelial cells keep order in the body by separating, anchoring and attaching to each other.  This information is remarkably vivid when applied to society as a whole; that is, our social ‘cells’ in terms of ‘tissues.’  it becomes a near poetry.

‘’Frederik Ruysch, working in the Netherlands, introduced the term epithelia in the third volume of his Thesaurus Anatomicus in 1703. Ruysch created the term from the Greek epi, which means on top of, and thele, which means nipple, to describe the type of tissue he found when dissecting the lip of a cadaver.’’

Epithelium is a sex organ, not just the lip or the nipple, but the sensitivity, the taste and smell.  We should be cherishing the linings of us while we live.

‘’Cell polarity refers to the intrinsic asymmetry observed in cells, either in their shape, structure, or organization of cellular components. Most epithelial cells, migrating cells and developing cells require some form of cell polarity for their function. These cells receive information about their surroundings via extracellular biochemical and mechanical cues and translate those information into polarity of the plasma membrane, its associated proteins and cytoskeletal organization. Once established, cell polarity is maintained by transcytosis, in which vesicles carry incorrectly-localized membrane proteins to the correct regions in the plasma membrane. In addition, tight junctions, which act as ‘fences’ against transmembrane diffusion, lock the asymmetry in place. Therefore, mechanobiology plays an essential regulatory role in both the establishment and maintenance of cell polarity.’’

Clearly we could use this set of functions to describe ‘citizen polarity’ — where each belongs and how to get them there.  This ought to be a concern of education.

‘’The apical  [apex= top] membrane faces the lumen [the channel or passage in the middle] and is rich in PAR and Crumbs protein complexes. The basolateral [bottom and sideways] membrane contains the Scribble complex and faces the extracellular matrix.

''The Scribble polarity complex or module is one of the three polarity modules that regulate cell polarity in multiple epithelia including blood-tissue barriers. This protein complex is composed of Scribble, Lethal giant larvae (Lgl) and Discs large (Dlg), which are well conserved across species from fruitflies and worms to mammals.''

Ah, if we could identify the human version of ‘lethal giant larvae’ while they are still children.  

NOTE THIS;  ACE2 must be enabled by the the cofactor TMPRSS2 to let a corona virus get into a cell.  

TMPRSS2 transmembrane serine protease 2 [ (human)]
This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain.’

So this is a human gene that has four parts; one about what goes across a membrane, one that receives, one that scavenges, and a protease (also called a peptidase or proteinase) which is an enzyme that catalyzes (increases the rate of) proteolysis, the breakdown of proteins into smaller polypeptides or single amino acids. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds.’ A very busy gene.

It was clear from early on that the linings of the lung alveoli were affected.  It’s only as the symptoms pile up that we see the hearts, lungs, kidneys, and guts — all lined with epithelial variations.  But that means we can search among whatever those epithelia had in common before they specialized, either through evolution or through gestation, something primal and therefore possibly can tip us off to something that can protect the whole system.  For all our love of binaries, we fail to recognize that there are two sides to every disease problem -- our side and the virus side.

https://www.livescience.com/coronavirus-not-human-made-in-lab.html

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