Your "ready-mix patch"

I will praise thee; for I am fearfully and wonderfully made: marvellous are thy works; and that my soul knoweth right well. Psalm 139:14

"You’ve probably used those packets with two compartments that do something when the dividing membrane is broken, allowing the

components to mix: instant heat, instant cold, instant glue, or instant light.
Your body has something like that to repair its tissues. Tissues are the webs of specialized cells that distinguish us multicellular organisms from the rest, and the bulk of tissues are composed of epithelium.
Epithelial cells line up in tightly-knit ranks forming the lining of most organs, the lungs and windpipe, the digestive tract, and the skin. Because they are subject to injury, these membranes must have a means of repairing themselves quickly. So they have a kind of ready-mix patch that works only when two components combine. But the system must work flawlessly, or a disaster can result.

Keith Mostov and Mirjam Zegers talk about this in the Mar. 20 issue of Nature, “Cell Biology: Just Mix and Patch,” reporting on work by Paola Vermeer and company in the same issue. Epithelial cells have two linings.
Consider the respiratory tract as an example.
*One lining, the apical side, faces the airway.
*The other, the basolateral side, lines the other end and the

neighboring cells.
These two linings are segregated by a kind of O-ring seal that makes a tight fit between neighboring cells.
Scientists recently found that the basolateral membrane has one component of the patch, called erbB2, and the apical side has a matching component called heregulin. Normally kept apart, they can be brought in contact when a breach occurs in the epithelial tissue.
*Together, they activate a complex series of steps leading to cell division and presto! the gap is filled in with another snug-fitting cell, and life goes on.
-- It is essential these active ingredients don’t mix at the wrong time. Too much cell division and you know what happens — cancer. Science Now has a news write-up on this story, and its discovery that is “so beautifully simple.”

A few more Cool Cell Tricks were reported recently: Cells have an exquisite toolkit for dealing with iron. Three New Zealand scientists writing a Perspective special feature in the Proceedings of the National Academy of Sciences describe a family of proteins called transferrins that clamp around iron and delicately transport this very toxic atom to wherever it’s needed in the cell. The clamp has a hinge that opens the structure and disgorges the iron when it is safe to do so.

Another protein called hemopexin transports heme by holding it in the center of a four-part structure.

Another Special Feature in the same issue talks about nitrogenase. Two Harvard chemists attack this puzzling molecule with the zeal of Captain Ahab pursuing Moby Dick (this is actually how they end their article), but in spite of the best efforts of scientists for decades, “Few problems in bioinorganic chemistry have proved as challenging and refractory.” They speak of techniques this molecule uses that are “biologically and chemically unprecedented,” and marvel. Hidden inside the inner sanctum of this molecular machine is a secret method for separating nitrogen atoms at room temperature that is the dream of agricultural chemists, because artificial nitrogen fixation (e.g., fertilizer making) is costly and energy intensive. “The synthetic problem of nitrogenase, nevertheless, remains unsolved,” but they think we’re getting warmer.

Current Biology for March 18 has a quick guide to a very versatile gene called APC (adenomatous polyposis coli), without which we either die or get colon cancer. It moves all over the cell, in and out of the nucleus, even riding the intracellular railroad. APC has many jobs. 

--It’s a potent tumor suppressor, 

--it regulates gene transcription, 

--and it has a role in “maintaining adherens junctions, and also helps to tether mitotic spindles to the cortex and to orient them in the epithelial plane. In mammalian cells, APC has been implicated in cell migration. APC also helps safeguard the fidelity of chromosome segregation in mitotic cells.”

Wow; a multi-talented kit. It appears to be essential for cell survival, too."
CEH

Nitrogenase: Another Blow to Evolution

He that sitteth in the heavens shall laugh: 

the Lord shall have them in derision.

Psalm 2:4

"Here’s the scoop: a complex reaction essential to life on earth has never been replicated by engineers, but it “emerged” in bacteria somehow, and has not evolved since.
Q: Does that sound like Darwinian evolution?
Nitrogenase is a true wonder of nature. 

This enzyme, found in certain bacteria, is able to break the tough

triple bonds in atmospheric nitrogen (N2), allowing plants to utilize the essential element found in every protein.

*Human engineers, eager to fix nitrogen for fertilizers, have to use a very energy-intensive process at high temperatures and pressures to break those bonds (the Haber-Bosch Process), but the bacteria do it easily at room temperature.

Q: How did this near-miraculous feat “emerge” in the world’s so-called simplest organisms, and why hasn’t it evolved? 

Therein lies a tale. It’s told in a preprint that appeared this month.

Nitrogenase resurrection and the evolution of a singular enzymatic mechanism (bioRxiv, 5 Feb 2023). Researchers at the University of Wisconsin and Utah State decided to look into the evolution of nitrogenase enzymes. When did they first appear? Is there an evolutionary sequence from a common ancestor? Here’s what they found, contradicting their assumptions about evolutionary “emergence” and

"The planetary biosphere is powered by a suite of key metabolic innovations that emerged early in the history of life. However, it is unknown whether life has always followed the same set of strategies for performing these critical tasks. Today, microbes access atmospheric sources of bioessential nitrogen through the activities of just one family of enzymes, nitrogenases. Here, we show that the only dinitrogen reduction mechanism known to date is an ancient feature conserved [i.e., unevolved] from nitrogenase ancestors."

*For their experiments, they used engineering (a form of intelligent

design). 

*They engineered what they consider an “ancestral” form of the enzyme and inserted it into a living bacterium. 

---If evolution were true, there should have been so many changes over billions of years that it would seem unlikely to work at all.....none of their explanation bears on how nitrogenase first appeared.

"Our results suggest that life may have been constrained in its sampling of protein sequence space to catalyze one of the most energetically challenging biochemical reactions in nature. The experimental framework established here is essential for probing how nitrogenase functionality has been shaped within a dynamic, cellular context to sustain a globally consequential metabolism."

They’re saying that however it “emerged,” nitrogenase was “constrained” from evolving because it had too important a job to do. 

So after some unexplained “emergence” (a virtual miracle without plan or foresight), it did not evolve further.
Q: But what is this “protein sequence space” they speak of?
A: It’s like a game of chance." 

CEH