Sunday, 26 January 2025
Here's what needs to happen before any of Christendom’s minions attempt to remove the straw from my eye.
Luke ch.6:42NIV"How can you say to your brother, ‘Brother, let me take the speck out of your eye,’ when you yourself fail to see the plank in your own eye? You hypocrite, first take the plank out of your eye, and then you will see clearly to remove the speck from your brother’s eye."
By it's fruits a tree is known
Acts ch.7:15-27NIV"“Watch out for false prophets. They come to you in sheep’s clothing, but inwardly they are ferocious wolves. 16By their fruit you will recognize them. Do people pick grapes from thornbushes, or figs from thistles? 17Likewise, every good tree bears good fruit, but a bad tree bears bad fruit. 18A good tree cannot bear bad fruit, and a bad tree cannot bear good fruit. 19Every tree that does not bear good fruit is cut down and thrown into the fire. 20Thus, by their fruit you will recognize them.
21“Not everyone who says to me, ‘Lord, Lord,’ will enter the kingdom of heaven, but only the one who does the will of my Father who is in heaven. 22Many will say to me on that day, ‘Lord, Lord, did we not prophesy in your name and in your name drive out demons and in your name perform many miracles?’ 23Then I will tell them plainly, ‘I never knew you. Away from me, you evildoers!’
24“Therefore everyone who hears these words of mine and puts them into practice is like a wise man who built his house on the rock. 25The rain came down, the streams rose, and the winds blew and beat against that house; yet it did not fall, because it had its foundation on the rock. 26But everyone who hears these words of mine and does not put them into practice is like a foolish man who built his house on sand. 27The rain came down, the streams rose, and the winds blew and beat agains"
Galatians ch.5:22,23NIV"But the fruit of the Spirit is love, joy, peace, forbearance, kindness, goodness, faithfulness, 23gentleness and self-control. Against such things there is no law."
Galatians ch.5:19-21NIV"The acts of the flesh are obvious: sexual immorality, impurity and debauchery; 20idolatry and witchcraft; hatred, discord, jealousy, fits of rage, selfish ambition, dissensions, factions 21and envy; drunkenness, orgies, and the like. I warn you, as I did before, that those who live like this will not inherit the kingdom of God."
Ps. No Spamming allowed,I hope I'm not talking over anyone's head.
The thumb print of JEHOVAH :molecular edition.
Recurring Design Logic in Gene Regulation
A feature of biology that has struck me over the years is the phenomenon of recurring design logic, even across systems that do not appear to be related by descent. This is a feature that is quite surprising on the supposition that a mindless process is responsible for life’s origins, but is precisely what we might predict on the hypothesis that a mind played an important role. In other realms of experience, when we encounter recurring design logic, we habitually associate it with intelligent causes. For example, there are features of paintings that characterize a particular painter’s work, and features of buildings that are common between edifices designed by the same architect. There are even aspects of one’s writing that are distinctive of an individual author. This, then, is an example of a prediction made by the hypothesis of purposeful design — something we expect to see on the supposition of the involvement of an intelligent mind. There are plenty of examples of this sort of phenomenon in biology. For illustration purposes, I will focus here on one class of recurring design logic — two-component regulatory systems in bacteria.
What Are Two-Component Regulatory Systems?
Bacterial cells use two-component systems to sense and respond to environmental changes. As their name suggests, two-component systems characteristically involve two components — a sensor kinase and a response regulator. The sensor kinase, in response to a chemical or physical stimulus, undergoes autophosphorylation, whereby a phosphate group is transferred from ATP to a histidine residue on the kinase. The histidine protein kinase has two domains: an input domain and a transmitter domain. The former is located on the outside of the cell, and is ideally situated to detect incoming environmental signals. The latter is situated on the cytoplasmic face of the cell membrane, and is positioned such that it can interact with the response regulator. The phosphate group is transferred to the response regulator, which then drives a cellular response, such as turning genes on or off.
Two-component systems are extremely common among bacteria, and each utilizes the same basic design logic. In what follows, I shall provide a short survey of a few such examples.
Regulation of Outer Membrane Proteins in Escherichia coli
A two-component system regulates the expression of porins in response to environmental osmolarity (a measure of the concentration of solute particles in a solution). The sensor kinase for this system, located in the inner membrane, is EnvZ. EnvZ detects osmolarity changes and undergoes autophosphorylation. The response regulator, OmpR, receives the phosphate group from EnvZ and regulates the expression of genes.
When osmolarity is high, the kinase activity of EnvZ is activated, resulting in the phosphorylation of OmpR. When osmolarity is low, the phosphatase activity of EnvZ is activated, reducing levels of phosphorylated OmpR.
Upon phosphorylation, OmpR becomes an active dimer that has enhanced DNA-binding ability specific to ompC and ompF gene promoters. These are are porin genes that encode outer membrane proteins (which allow the passage of metabolites across the outer membrane of gram-negative bacteria). The pore diameter of OmpF is larger than OmpC. This allows for a ten-fold faster diffusion rate, which is advantageous under conditions of low osmolarity where nutrients are scarce. If osmotic pressure is low, the synthesis of OmpF is increased. If osmotic pressure is high, the expression of OmpC is increased. Moreover, transcription of micFantisense RNA is initiated. micF blocks translation of ompF by complementary binding – the synthesis of OmpF is thereby repressed.
Regulation of Chemotaxis
Bacteria are able to move towards a food source, such as glucose, by a process known as “chemotaxis.” A requisite for this process to work is the ability of the bacterial flagellar motor to literally shift gears so that it switches from spinning counter-clockwise to rotating clockwise. This change in rotation is brought about in response to chemical stimuli from the cell’s exterior. These chemical signals are detected by a two-component signal transduction circuit that operates to induce the switch in flagellar rotation.
Readers may find it helpful to refer to the following diagram while reading the descriptions that follow:
Image credit: Wikimedia Commons
How do bacteria detect a chemical gradient? The answer lies in a certain class of transmembrane receptors called methyl-accepting chemotaxis proteins (hereafter, MCPs). Different MCPs can detect different types of molecules, and are able to bind attractants or repellents. These receptors then communicate with — and activate — the so-called “Che proteins.”.
Proteins called CheA and CheW are bound to the receptor. The former is the histidine kinase for this system. Upon activation of the receptor, the CheA’s conserved histidine residue undergoes autophosphorylation. There are two response regulators called CheB and CheY. There is a transfer of a phosphoryl group to their conserved aspartate residue from CheA. CheY subsequently interacts with the flagellar switch protein called FliM. This induces the switching in flagellar direction from counterclockwise to clockwise.
This clockwise rotation upsets the entire flagella bundle and causes it to break up. The result is that the bacterium “tumbles.” This means that bacteria are able to re-direct their course and repeatedly re-evaluate and adjust their bearings in response to environmental stimuli such as food or poisons.
As for the other response regulator I mentioned, CheB, what does it do? When CheB is activated by the histidine kinase CheA, it operates as a methylesterase. This means that it actively removes methyl groups from glutamate residues on the receptor’s cytoplasmic surface. Meanwhile, another protein (called CheR) actively adds methyl residues to these same glutamate residues — that is to say, it works as a methyltransferase.
At this point the engineering shows a stroke of genius. If the stimulus is at a high level, there will be a corresponding decline in the level of phosphorylation of the CheA protein — and, as a consequence, of the response regulators CheY and CheB as well. Remember that the role of CheB is to remove methyl groups from glutamate residues on the receptor’s cytoplasmic surface. But now, phosphorylated CheB is not available and so this task is not performed. The degree of methylation of the MCPs will thus be raised. When the MCPs are fully methylated, the cell will swim continuously because the MCPs are no longer responsive to the stimuli.
This entails that the level of phosphorylated CheA and CheB will increase even when the level of attractant remains high, and the cell will commence the process of tumbling. But now, the phosphorylated CheB is able to demethylate the MCPs, and the receptors are again able to respond to the attracting chemical signals. In the case of repellents, the situation is similar — except that it is the least methylated MCPs which respond least while the fully methylated ones respond most. This kind of regulation also means that the bacterium has a memory system for chemical concentrations from the recent past and compares them to its currently receiving signals. It can thus detect whether it is moving towards or away from a chemical stimulus.
Quorum Sensing
The purpose of quorum sensing is essentially to ensure that sufficient cell numbers of a given species are present before initiating a response that requires the population density to be above a certain threshold. A single bacterial cell secreting a toxin into a eukaryotic organism is not likely to do the host any harm and would waste resources. If, however, all of the bacterial cells in a large population co-ordinate the expression of the toxin, the toxin is more likely to have the desired effect.
Each species that employs quorum sensing — which includes most gram-negative bacteria, and also some gram-positive bacteria — synthesizes a tiny signaling molecule (technically called an “autoinducer”), which diffuses freely across the cell’s membrane. Autoinducers are species-specific, which means that each cell of the same species makes the same molecule. This means that the autoinducer is only present in high concentrations inside the cell when there are many cells of the same species nearby. Inside the cell, the autoinducer binds to an activator protein which is specific for that particular molecule and thus signals the bacteria to begin transcription of specific genes.
For example, consider the case of the bioluminescent bacterium, Aliivibrio fischeri (pictured at the top of this article). The light that this species of bacteria emits results from the action of the enzyme, luciferase. An activator protein, called LuxR, is responsible for controlling the lux operons, which are in turn responsible for the transcription of the proteins required for luminescence. These operons are induced when the concentration of the autoinducer specific to Aliivibro fischeri reaches a high enough concentration. This autoinducer is itself synthesized by the enzyme which is encoded by the LuxI gene.
Image credit: Wikimedia commons
Quorum sensing is very widespread, particularly in gram negative bacteria. Pseudomonas aeruginosa, for example, uses such “population sampling” processes to trigger the expression of a significant number of unrelated genes when the population density reaches a certain threshold. These genes subsequently allow the cells to form a biofilm (which increases the pathogenicity of the organism and prevents the penetration of antibiotics). See the figure above on the role of two-component quorum sensing in bacterial biofilm formation
Recurring Design Logic
Here, I have described only a few examples of two-component regulatory systems, of which many more examples could be provided. Across these diverse systems, we see a recurring design logic, despite the fact that these systems are not related by evolutionary descent. This is precisely what we might expect to see if the same intelligent mind was involved in their origins, but is really quite surprising on the postulate of an undirected process of chance and physical necessity
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