My articles

Confirmation bias & willful ignorance: How to deal with it

“My-side bias” makes it difficult for us to see the logic in arguments we disagree with
https://digest.bps.org.uk/2018/10/09/my-side-bias-makes-it-difficult-for-us-to-see-the-logic-in-arguments-we-disagree-with/?fbclid=IwAR2lSycCHV2zcsypkyJb8h9-E47aTMycJOi881-ETOuhyAfgHKNFgest940
“Our results show why debates about controversial issues often seem so futile,” the researchers said. “Our values can blind us to acknowledging the same logic in our opponent’s arguments if the values underlying these arguments offend our own.”



Atheists, in most, if not all cases, aren't looking for evidence of Gods existence or proof. They are looking to find reasons that confirm what they want to be true. They look for validation. What they want, is to avoid God and find relief to justify to themselves what they want to be true.  They aren't interested in arguments, but when a theist makes them, the only aim is to find ways to refute and reject what points to a creator. It is called confirmation bias. Wiki: Confirmation bias, also called confirmatory bias or myside bias is the tendency to search for, interpret, favor, and recall information in a way that confirms one's preexisting beliefs or hypotheses. It is a type of cognitive bias and a systematic error of inductive reasoning. People display this bias when they gather or remember information selectively, or when they interpret it in a biased way. The effect is stronger for emotionally charged issues and for deeply entrenched beliefs.

Many unbelievers find it intellectually more justified or defendable not to declare themselves openly as ( strong ) atheists. They do want to avoid the burden of proof -  they know it would bring their position into trouble.  They know that all no - God hypotheses are intellectually bankrupt and easy to shut down. There are no good reasons to apply Occam's Razor to God. So they either duck cowardly and say: I do not hold an epistemologically elaborated position - I just do not believe yours. They try to sell their fish like this:  "

We replace God with honesty by saying "we don't know". The fact that we don't currently know does not mean we will never know because we have science, the best method we have for answering questions about things we don't know. Simply saying "God did it" is making up an answer because we are too lazy to try to figure out the real truth."

Sounds nice, but engaging a theist just to try to bring him down to unbelief without offering a better alternative, without any real intention to actually honestly consider and evaluate his beliefs means to waste his time and behaving egoistically, to use him to solidify his unbelief in God. What he does not realize, that, by doing so, all he is doing, is a way of self-delusion. We, believers in the promises of Christ, know, that our efforts make sense, independently if the counterpart considers our light of truth, or not, because of 1. Our words can germinate one day. Atheists do not forget, and in a particular, future situation, when they are more open, they can remember, and the information can help them to come to God. And 2. The ones that reject the truth and die without coming to Christ, cannot justify that they did not be called to come to repentance. If they get lost, it's their fault. Not Gods, or his servants which did not follow Christs calling to go to the world to preach the gospel.

Then, besides the weak atheists, we have the  " We don't know-ists. ".  They proudly do put on display their willful ignorance like the adornment of a peacock and feel that trumpet it to the world how little they know about origins is not only a beautiful but intellectually very scholar and worth of admiration. They put things upside down and don't realize that their position is a sublime admittance of brainlessness, laziness, and irrational blindness, not smart, but on the contrary: intellectually disturbing. But their real motivations are clear. They express just another form of confirmation bias and use another tactic to justify their unbelief. Their cognitive dissonance which they obviously do not admit is obvious, we are not ignorant of it.

For this reason, not rarely, when an atheist or agnostic has exposed, what his motivations are, it makes no sense for a theist to engage such a person for much time. I have a long list of people that I blocked, because, they cannot handle the fact that their motivations have been exposed, and not rarely, they lowered the level to personal attacks. My way to deal with it is either blocking, or saying goodbye, and not engaging further. Our time is precious.

There are many out there that need their faith to be strengthened. And providing evidence in Creation that points to God is a formidable way.

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Atheism & Self-delusion

I think the problem with spiritually blinded people is that they are so blinded that they have no idea how blinded they are. If they're totally spiritually blind, how can you possibly realize that they are blind? They'd have to realize how blind they are.  In order to know how blind they are, it requires visual skills in order to compare which means that if they're absolutely no good at seeing at all then they lack exactly the skills that they need to know that they're absolutely no good at sight and this explains not just atheists but the condition of almost the entire pantheon and various breeds of unbelievers. There is no worse blind man than the one who doesn’t want to see. The precondition to see is the will to see. Then God can open their eyes, and they realize where they were.

John 3.19: This is the verdict: Light has come into the world, but people loved darkness instead of light because their deeds were evil.

John 12.40: He has blinded their eyes and hardened their hearts, so they can neither see with their eyes, nor understand with their hearts, nor turn—and I would heal them.

2 Corinthians 4:4: In their case the god of this world has blinded the minds of the unbelievers, to keep them from seeing the light of the gospel of the glory of Christ, who is the image of God.

2 Corinthians 4:6 For God, who said, “Let light shine out of darkness,” has shone in our hearts to give the light of the knowledge of the glory of God in the face of Jesus Christ.

2 Corinthians 4:3-4 And even if our gospel is veiled, it is veiled only to those who are perishing. In their case the god of this world has blinded the minds of the unbelievers, to keep them from seeing the light of the gospel of the glory of Christ, who is the image of God.

The human heart is the hardest thing in the universe, harder than Iron. Harder than diamonds. We shall not expect it to change just because we have irrefutable evidence that there is a Creator. But God does miracles. Even today. If he turned a Saul into a Paul, he can draw even the most hardened atheist to him.

Acts 17:30
In the past, God overlooked such ignorance, but now he commands all people everywhere to repent.

Ezekiel 36:26
"I will give you a new heart and put a new spirit within you; I will take the heart of stone out of your flesh and give you a heart of flesh."

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I see it over and over: Atheists are throughout defeated in their reasoning that our existence can be explained without a creator. But once all arguments are exhausted, and they find themselves in a situation, where they cannot sustain what they tried to justify, rationally, they need to face the brute fact that God exists. And this situation demands that they make a decision. That is where will kicks in. C.S.Lewis brought it straight to the point, when he wrote, that atheists look for God, like a thief for the police station. A honest agnostic seeker, after his journey, and evaluating all evidence, has to come without doubt to the conclusion that Theism is the best answer after a critical analysis of the evidence that surrounds us. That brought Anthony Flew to abandon his views, and endorse deism. The quest of God IS one that demands us rationally to search him. An irrational worldview can only perpetuate based on blind faith, which unfortunately all to often is the case. But a worldview , to be true, must withstand rational, philosophic, and scientific scrutiny.

Many atheists, however, become misotheists, or indifferent altogether towards questions of origins, and God. We are often accused of making baseless claims when we point out why atheists are atheists. I agree everyone has its personal reasons and motivations. But a general picture can be outlined. An atheist, which cannot sustain his views rationally, rejects God because of will. He does not WANT ( will ) God in his life. He thinks life without God is better. He has the ( false ) perception and imagination that life without God will provide more freedom. And that it is not worth to obey a higher entity, whatever his laws are. Another reason is: Statistically, it is proven, that most people define their position in regards to religion when they are young. Older people are accustomed to a certain lifestyle and see no necessity of change.

In the end, the big issue is spiritual. Surrender to God is a spiritual event and transition, that is provoked by the change and moving of the "heart" ( or your inner being ), moving from a spiritual dead life to a spiritual awakening, where God begins to dwell, interact, and live in the life of a believer.

I also think, God in his wisdom, wanted it so: It would not be just if people of higher intelligence would have an advantage over people with less IQ/education/instruction. So God made our position to HIM a quest of our heart, a moral decision. So there is equality. Even people with a certain mental deficiency can find and worship God, and become his children. 

What a blessing experience of all those, which have had the courage to be persuaded by Gods love and grace !!

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An atheist is NOT an atheist for the reason that there is not enough evidence of Gods existence.

An atheist is so essentially because of will. He might have a distorted view about who God is ( like Richard Dawkins ), or simply because he does not want a higher being in his life which says the direction, and gives moral rules). Whatever. They want to be their own "highest being" and live autonomously from God. Their rationalization that there is not enough evidence of Gods existence is just a way to justify to themselves, what they already want to be true since the cognitive dissonance and poking of their conscience from time to time must be appeased somehow.

When we demonstrate that they borrow from the theistic worldview to make sense of their own ( there cannot be objective moral values without God, nor any reason of existence, nor can they trust their own logic and thinking process )  we apply classical apologetics.

As an automatical reaction, when confronted with the logical inference of creation upon the evidence in scriptures, and the natural world, besides of logical reasoning and philosophy, all they will do, is try to find counter-arguments to reject what they do not want to be true. Our dialogue will sharpen their cognitive dissonance and discomfort for a while because they know their position is notwithstanding scrutiny. But time has its effect.  They will soon forget what they heard and move on without seeking God. Business as usual.

BUT: If at a different moment in time, they change their attitude, and for one reason or another, start to seek for God, what they know already, can be of help. That includes 1. Reasons that they know why theism makes sense, and 2. how they feel they were treated by the other side ( us, believers. Is the other team attractive to make part, are they nice? ) That's why it is important they can see the difference of how we treat our next. With love, justice, and respect.

So, in the end, who draws the unbeliever to Christ, is the holy spirit. We are called to proclaim the gospel, to pray for unbelievers, and trust that the Lord will reach his goals to form the  " Body of Christ, his bride".

1, Corinthians 9.20: 20 To the Jews I became like a Jew, to win the Jews. To those under the law I became like one under the law (though I myself am not under the law), so as to win those under the law. 21 To those not having the law I became like one not having the law (though I am not free from God’s law but am under Christ’s law), so as to win those not having the law. 22 To the weak I became weak, to win the weak. I have become all things to all people so that by all possible means I might save some. 23 I do all this for the sake of the gospel, that I may share in its blessings.

1 Peter 3.15: Always be prepared to give an answer to everyone who asks you to give the reason for the hope that you have. But do this with gentleness and respect,

Are factories made by intelligent professionals, or unguided unconscious random processes ?

https://reasonandscience.catsboard.com/t2061p125-my-articles#6163

Do we need to see architects, engineers, programmers, coordinators, instructors, managers, specialists, regulators, fine-tuners, interpreters etc. in action, building factories,  to conclude a factory was made by intelligent professionals? Or can we conclude design and intelligent setup as the best explanation when we see a factory in operation?

Engineering requires an engineer
Architecture requires an architect
An orchestra requires a Director
Organization requires an organizer
Setting up a programming language requires a programmer
Setting up Information selection programs require Search and Selection Programming engineers
Setting up translation programs requires translation programmers
Creating communication systems require  Network engineers
Electrical networks require electrical engineers
Logistics require a logistic specialist
Modular organization requires a Modular project manager
Setting up recycling systems require a recycling technician
Setting up power plants requires Systems Engineers of Power Plants
Nanoscale technology requires Nano Process Development Engineers
Product planning and control require a Production Control Coordinator
Establishing product Quantity and Variant Flexibility require product management engineers
Waste management require a waste logistics manager
Creating a language requires intelligence
Creating Instructional information requires an Instructor
Coordination requires a coordinator
Setting up strategies requires a strategist
Regulation requires a regulator
Controlling requires intelligence that sets up and programs the automatic control functions
Recruiting requires intelligence which instructs autonomous programs how to do it.
Interpretation requires intelligence which creates an interpretation program.
Switch mechanisms with on and off states require intelligent setup.
Setting up transport highways requires  Transportation Development engineers
Controlled factory implosion programming requires an Explosive Safety Specialist

Biological Cells do all above described, but no intelligence to set up all these things is required?

Objection: We have never observed a being of any capacity creating biological systems and life.  
Answer: We do not need direct observed empirical evidence to infer design. As anyone who has watched TV's Crime Scene Investigation knows, scientific investigation of a set of data (the data at the scene of a man's death) may lead to the conclusion that the event that produced the data (the death) was not the product of natural causes not an accident, in other words but was the product of an intelligence a perpetrator.
But of course, the data at the crime scene usually can't tell us very much about that intelligence. If the data includes fingerprints or DNA that produces a match when cross-checked against other data fingerprint or DNA banks it might lead to the identification of an individual. But even so, the tools of natural science are useless to determine the I.Q. of the intelligence, the efficiency vs. the emotionalism of the intelligence, or the motive of the intelligence. That data, analyzed by only the tools of natural science, often cannot permit the investigator to construct a theory of why the perpetrator acted.  Sherlock Holmes can use chemistry to figure out that an intelligence a person did the act that killed the victim, even if he can't use chemistry to figure out that the person who did it was Professor Moriarty, or to figure out why Moriarty did the crime.
Same when we observe the natural world. It gives us hints about how it could have been created. We do not need to present the act of creation to infer creationism / Intelligent design.

Atheists err when asking for material evidence to prove God's existence
https://reasonandscience.catsboard.com/t2256-atheists-err-when-asking-for-material-evidence-to-prove-god-s-existence

Question for an atheist. Are you a non-believer because you cannot see, hear or touch God? or is it for other reasons?
If it is because you cannot prove there is a God, I want to propose another question.
But first, try this out.
Say "I love tasty food," but don't actually try to physically make an effort to say it. Use your mind to say it.
Okay, what exactly did you just do and how is it that you can hear yourself so clearly in your own mind. There is an action (you saying the statement) and its existence is clear to you, but to us that sentence that you just said "out loud" in your head doesn't exist to us.
Matter of fact I will ask you, right now, to prove to me that you just said, "I love tasty food," in your head.
Telling me you said that statement isn't showing me evidence as to its existence. Some of you may say, "Hey, well it is dumbass." Ok, I understand how that can be a compelling argument. Now lets consider that I may lie to you and tell you that I did say I love tasty food consciously, but I actually didn't. Well then, the physical act of telling someone you thought something isn't the most viable way of showing evidence as to what you actually thought. Therefore isn't proving anything.
To get to the point, I want to say that there are probably lots of things that don't physically exist in our world, but have an existence. Just because you can't prove something doesn't mean it doesn't exist.
hopefully food for thought.

Creation of the Earth vs Heaven

Exodus 20:11
"For in six days the LORD made the heavens and the earth, the sea and all that is in them, and rested on the seventh day; therefore the LORD blessed the sabbath day and made it holy.

John 14:2
“Do not let your hearts be troubled. You believe in God; believe also in me. My Father’s house has many rooms; if that were not so, would I have told you that I am going there to prepare a place for you? And if I go and prepare a place for you, I will come back and take you to be with me that you also may be where I am.

1 Corinthians 2
“What no eye has seen, what no ear has heard, and what no human mind has conceived”—the things God has prepared for those who love him
If God created the universe and the earth in six days, can you imagine how beautiful for Christ's bride, the redeemed Church, you and me, the place he is preparing for us, will be? Christ resurrected and went to heaven two thousand years ago, and said, while he is not returning to take us home to heaven ( the Earth is just a passage place for all of us, but in special for the redeemed Church and all that belong to HIM) , he is preparing a place for us to stay with him - forever. That is, 730000 days, he is already preparing !!! He is already now, preparing 120 thousand times longer than he was when he made the earth !! - and what amazingly beautiful world that must have been prior the fall - we have still today a glimpse of it - and he still working on our heavenly place !! Yup - great plans God has for us - little unfaithful sinners that transgress his will with such ease, and so often demonstrate so little love for him.

His care and incomprehensible love for us should humble us to stay and seek more his face, and aim to do his will, and demonstrate our love towards the one that came to suffer and give his Life on our behalf, to save us from the torment that God deniers and God haters face in eternity - what great salvation - he had truly all reasons to exclaim before the moment he was to give up his spirit and died: It's done !!

His sacrifice is truly incomprehensible for us. The Almighty One, the great I AM, Supreme Creator Over All, the King of Kings, Lord of all, Lion of the Tribe of Judah, the ruler, the lofty one, the one reigning for all eternity, nobody above him, the Alpha and Omega, the first and the last, the all-powerful, the holy and just God, creator of the heavens and the earth, billions of angels serving him day and night, became our Redeemer, the Lamb of God, a humble man, being born in nobody land, Nazareth, a small place of no importance in the Roman Empire.

http://www1.cbn.com/…/five-things-you-didnt-know-about-naza…
Nazareth was the original small town. in Jesus' day, only 120-150 people lived in Nazareth. In John 1:46, Nathanael asked the famous question, "Can anything good come out of Nazareth?" This tiny farming village, high on a hill and far from the main trade routes, was the last place anyone would look for the Messiah of Israel. Unless they were smart enough to figure out the following prophecy....
Isaiah prophesied that the Messiah would come from Nazareth about 600 years before the village existed.
In the 8th century before Christ's birth, Isaiah prophesied that "a shoot will spring from the stem of Jesse, and a branch from his roots will bear fruit" (Isaiah 11:1). The word "branch" in Hebrew is netzer, the same root word from which the name "Nazareth" comes. Some historians have suggested that Nazareth was named as "the town of the branch," meaning "the place where the Branch of David lives." In the New Testament, Matthew connects Nazareth with the prophecy in Isaiah 11:1: "And came and resided in a city called Nazareth, that what was spoken through the prophets might be fulfilled, ‘He shall be called a Nazarene’" (Matthew 2:23).

Nazareth was a small town, disdained by others, and the Messiah grow in a humble and poor family, walked amongst us, and to die naked ( yes, in order to humiliate they were crucified naked )

As J. Vernon McGee (Thru the Bible) says:
He was crucified naked. It is difficult for us in this age of nudity and pornography to comprehend the great humiliation He suffered by hanging nude on the cross. They had taken His garments and gambled for ownership. My friend, He went through it all, crucified naked, that you might be clothed with the righteousness of Christ, and so be able to stand before God throughout the endless ages of eternity.
He was humiliated and exposed to the most painful torture invented by man.

https://theologyarchaeology.wordpress.com/…/06/12/crucifix…/
• Cicero described crucifixion as “the cruelest and most terrible punishment” (Verr. 2.5.165).
• Josephus called it “the most pitiable of deaths” (J.W. 7.203).
Ancients also considered crucifixion to be the ultimate shame. For example, Celsus, the second-century ad detractor of Christianity, wrote that Jesus had been executed in a “dishonorable and shameful way” (Origen, Cels. 6.10). The author of Hebrews wrote that Jesus “endured the cross, disregarding the shame” (Heb 12:2). In crucifixion, everything was done to humiliate and dishonor the victim in addition to torturing him or her to death.
Christ went through all this, to take your sins my sins, all our sins, of all humanity, and pay the price of sin: death. The just and sinless, dying for sinners.
Seek him more and love him more. Lift up your face and contemplate his goodness - he is good and good-hearted - despite all our rebellious ways, he loves and keeps loving us.
But he is not weak, but strong and powerful - and just. A courageous warrior - if you make HIM your enemy - he is the worst you can imagine.

Hebrew 10.31:
For we know him who said, “It is mine to avenge; I will repay,” and again, “The Lord will judge his people.” It is a dreadful thing to fall into the hands of the living God.
His justice will always prevail, and his enemies will all perish, soon or later.

Psalm 94:15
For justice will prevail,
and all the morally upright will be vindicated.

There is no more foolish behavior than to deny and reject him - just to seek living without someone above that wants to direct our lives and orient us - to the better. To live a meaningful and blessed life. Better you make peace and surrender before its too late !! If you walk on the street today and cross the street, and a car does not see you, you can suffer an accident, the car hits you, and die. Where will you go? How can you face eternity without making peace with your creator, here - before its too late? - he is not asking you to start doing miraculous things - he just wants that you surrender to his grace, repent, and start following HIM, and orient your ways towards HIS direction - his will for us is always the best way. He is all-knowing and has a plan for us. For me, and for you. He deserves our trust. If he made life and all that surrounds us, do you think he does not know better than you, what is good for you? Why insisting on living a meaningless egoistic rebellious life, outside of the will of your creator - the only end station will the death ??

1 Chronicles 16:23-31
Sing to the LORD, all the earth; proclaim his salvation day after day. Declare his glory among the nations, his marvelous deeds among all peoples. For great is the LORD and most worthy of praise; he is to be feared above all gods. For all the gods of the nations are idols, but the LORD made the heavens. Splendor and majesty are before him; strength and joy are in his dwelling place. Ascribe to the LORD, all you families of nations, ascribe to the LORD glory and strength. Ascribe to the LORD the glory due his name; bring an offering and come before him. Worship the LORD in the splendor of his holiness. Tremble before him, all the earth! The world is firmly established; it cannot be moved. Let the heavens rejoice, let the earth be glad; let them say among the nations, “The LORD reigns!”
Come and let us sing the Lord together. Hallelujah !! Maranatha.

We all are subdued to the inescapable fact that we depend on faith to make sense of the reality which surrounds us.
There are no unbelievers.
There are believers which are correct, and believers that are incorrect in regards to our origins.
There are believers in God, and there are believers that the natural world is all there is.
Agnosticism as a state of constant being is not justified.
To know anything someone needs to have faith.
Faith in sensory perception,
faith in rational ability,
faith in the uniformity of nature.
Without faith, we couldn't function in society.

Gödel's incompleteness theorem

https://reasonandscience.catsboard.com/t1298-godel-s-incompleteness-theorem

Nearly all scientific laws are based on inductive reasoning. These laws rest on an assumption that the universe is logical and based on fixed discoverable laws. You cannot PROVE this. (You can’t prove that the sun will come up tomorrow morning either.) You literally have to take it on faith. In fact most people don’t know that outside the science circle is a philosophy circle. Science is based on philosophical assumptions that you cannot scientifically prove. Actually, the scientific method cannot prove, it can only infer. (Science originally came from the idea that God made an orderly universe which obeys fixed, discoverable laws.) Now please consider what happens when we draw the biggest circle possibly can – around the whole universe. (If there are multiple universes, we’re drawing a circle around all of them too):

There has to be something outside that circle. Something which we have to assume but cannot prove
The universe as we know it is finite – finite matter, finite energy, finite space and finite time
The universe is mathematical. Any physical system subjected to measurement performs arithmetic. (You don’t need to know math to do addition – you can use an abacus instead and it will give you the right answer every time.)
The universe (all matter, energy, space and time) cannot explain itself
Whatever is outside the biggest circle is boundless. By definition it is not possible to draw a circle around it.
If we draw a circle around all matter, energy, space and time and apply Gödel’s theorem, then we know what is outside that circle is not matter, is not energy, is not space and is not time. It’s immaterial.
Whatever is outside the biggest circle is not a system – i.e. is not an assemblage of parts. Otherwise we could draw a circle around them. The thing outside the biggest circle is indivisible.
Whatever is outside the biggest circle is an uncaused cause, because you can always draw a circle around an effect.

Why is there.....

Why are there bipedals, if there are still quadrupeds?
Why are there still tetrapods, if there are quadrupeds?
Why are there still tetrapods, if there are still lobe-finned fishes?
Why are there lobe-finned fishes, if there are ray-finned fishes?
Why did paired fins derive and evolve from gill structures?
Why do gills in jawless animals such as lampreys form from the embryo's innermost layer of cells, or 'endoderm', whereas in jawed vertebrates, including many fish species, from the outermost layer, or 'ectoderm'?
Why are there skeletons, if there are still crustaceans with exoskeletons?
How could there have been a transition from invertebrates to vertebrates, if bone formation is an irreducibly complex process?
Why are there still marine worms, if there are crustaceans?
Why are there still annelid worms, if there are still Arthropods?
If there are hominoids, why are there still fish?

Its co-option, lateral gene transfer, parallel evolution, convergent evolution, genetic drift, gene flow, natural selection, antigenic drift, and a sprinkle of imagination, dude !! If you didn't know, go and learn how evolution works !!

A walk through the epigenetic landscape which regulates Gene expression points to the requirement of intelligent setup and design

Following article is better read here:
https://reasonandscience.catsboard.com/t2061p125-my-articles#6169

The gene regulatory network
https://reasonandscience.catsboard.com/t2590p25-origins-what-cause-explains-best-our-existence-and-why#6153

Life is built upon an instructional blueprint stored in the Genome, through DNA, but also higher order epigenetic codes and languages ( various information layers, one above the other ) signaling and information transmission networks, which regulate which information in the genome has to be expressed or repressed, and when. Each gene section has a start and stop - promoter sequence, which informs the transcription machinery ( RNA polymerase ) when to start, and when to stop transcribing a specific gene. The regulation, when and where to do so, depends on the Gene regulation network.

The ultracomplex cellular machinery, responsible for it, has been traditionally a little bit less in focus than everything that happens in genomics because of evolution. Science is still pretty much, in the beginning, to unravel how epigenetic regulatory networks work. The complexity is just phenomenal, and nothing short of amazing - and shifting the make of phenotypes to higher - epigenetic, rather than only genetic information, and as such, the mechanisms that govern the making of bodies, depend on various molecular processes and protein complexes, signaling and information networks, which are best described through structuralism, which is an umbrella name for different mechanisms that guide the formation of body plans, in the center of all, EPIGENETIC INFORMATION AND VARIOUS EPIGENETIC CODE SYSTEMS AND LANGUAGES.

Epigenetics is one of the hottest fields in the life sciences. It’s a phenomenon with wide-ranging, powerful effects on many aspects of biology. Epigenetics is essentially additional information layered on top of the sequence of letters (strings of molecules called A, C, G, and T) that makes up DNA. If you consider a DNA sequence as the text of an instruction manual that explains how to make a human body, epigenetics is as if someone's taken a pack of highlighters and used different colors to mark up different parts of the text in different ways. For example, someone might use a pink highlighter to mark parts of the text that needs to be read the most carefully, and a blue highlighter to mark parts that aren't as important.

Genes are regulated by epigenetic networks, which includes heritability, as it defines a nongenetic memory of function that is transmitted from generation to generation.

Epigenetic information very much defines how bodies are built, and that shifts the quest of biodiversity from genes, and genetic information, to epigenetics. One gene section can be expressed upon different splicing through the spliceosome machinery, for example in human cells, 300 times differently, that means the product of 300 different functional proteins species can be and are produced. 20 thousand genes in the human genome can synthesize 6 million different protein species !! Where did the instruction come from to generate the splicing code and language which governs and directs the right gene splicing?

Back to gene regulation. 
Regulation of gene expression includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA),  Sophisticated programs of gene expression are widely observed in biology, and they need to be able to permit:

Developmental pathways
- Developmental pathways are networks of genes that act coordinately to establish the body plan. Disruptions of genes in one pathway can have effects in related pathways and may result in serious dysmorphogenesis or cancer.

Cells can change dramatically, following a definite developmental pathway: that’s what happens in cell differentiation, for example from a hematopoietic stem cell to differentiated blood cells like lymphocytes, monocytes, neutrophils, and so on. The end of the differentiation is the final differentiated cell, which is in a sense more “stable”, having reached its final intended “form”.

Respond to environmental stimuli
- The ability to change over time in response to the environment is fundamental and is determined by the organism's genetics. A living organism must be able to respond appropriately to external/environmental stimuli; A response can take many forms, from the contraction of a unicellular organism to external chemicals to complex reactions involving all the senses of multicellular organisms. An example of responding to stimuli is a bacterium forming an endospore when exposed to tough, unfavorable conditions to protect itself

Adapt to new food sources
- All organisms need to adapt to their habitat to be able to survive.

Those “stable” differentiated cells, however, are still in a continuous flow of informational change, which is still drawn by continuous modifications in the transcriptome/proteome and in chromatin configurations. Even if these changes are less dramatic, and do not change the basic identity of the differentiated cell, still they are necessary to allow adaptation to different contexts, for example varying messages from near cells or from the rest of the body, either hormonal, or neurologic, or other, or other stimuli from the environment (for example, metabolic conditions, stress, and so on), or even simply the adherence to circadian (or other) rhythms.  "Stable"cells are not stable at all: they change continuously while retaining their basic cell identity, and those changes are, again, drawn by continuous modifications in the transcriptome/proteome and in the chromatin configurations of the cell.

These are requirements for all life forms, and cells must be able to deal with all three requirements. If they cannot respond to environmental stimuli - no life. If they cannot adapt to new food sources - no life. If they have no programmed development pathways - no life.

The result of this machinery and of its workings is that thousands of proteins are transcribed and translated smoothly at different times and in different cells. 

Any step of gene expression may be modulated, from the DNA-RNA transcription step to post-translational modification of a protein. The following is a list of stages where gene expression is regulated, the most extensively utilized point is Transcription Initiation:

- Chromatin domains
- Transcription
- Post-transcriptional modification
- RNA transport
- Translation
- mRNA degradation

The mechanisms upon which gene expression relies, that is Gene repression or activation, the basis of the epigenetic landscape of a cell encompasses

- DNA methylation
- histone modifications
- histone variants
- nucleosome positioning

Epigenetic plasticity is further regulated by the three-dimensional and higher-order chromatin structure, including nucleosome repositioning, DNA looping, and long-range chromatin interactions.

The above different mechanisms that control these epigenetic changes do not stand alone, and there are a clear interconnection and interdependency between them.

Interdependence means, if one of the three mechanisms is not present, the others cannot function properly. And if the modifications do not occur as they should, cancer and other diseases are the consequence. Which demonstrates that a gradual stepwise increase in complexity was not possible. These mechanisms are interlocked and had to emerge fully developed and properly functioning right from the beginning. 

The interaction between transcriptome/proteome and chromatin configuration is an interaction. The transcriptome/proteome determines the chromatin configuration in many ways: for example, changing the methylation of DNA (DNA methyltransferases); or modifying the post-transcriptional modifications (methylation, acetylation, ubiquitination and others) of histones (covalent histone-modifying complexes), or creating new loops in chromatin (transcription factors); or directly remodeling chromatin itself (ATP-dependent chromatin remodeling complexes). In the same way, any modification of the chromatin landscape immediately influences what the existing transcriptome/proteome is and can do, because it directly changes the transcriptome/proteome as a result of the changes in gene transcription. Of course, this can modify the availability of genes, promoters, enhancers, and regulatory regions in general at chromatin level.

Remarkable is, that all these molecular systems depend on epigenetic languages, and the ability to interpret signals. That means cells must be able to interpret, react, transmit, and receive both, internal and external information and stimuli, and a signaling network must be fully set up. Receptors on the Cell membrane ( there are many different ones ) receive external information, and signals are transmitted to the machinery which receives, interprets, understands, and activates various responses. Corepressor/coactivator exchange complexes are targets of multiple extracellular and intracellular signaling pathways.

In communication, by definition, four things need to exist:

1. A code
2. An encoder that obeys the rules of a code
3. A message that obeys the rules of the code
4. A decoder that obeys the rules of the code

These four things—language, the transmitter of language, message, and receiver of language—all have to be precisely defined in advance before any form of communication can be possible at all. This is an interdependent irreducible system.

DNA methylation depends on the DNA methylation code and language. Histone modifications depend on the Histone Code, which is governed by protein readers, writers, editors, and erasers, and there is even combinatorial readout of and cross-talk between post-translational modifications ( PTMs ) of histone tails. That can occur between the eight histone tails of a nucleosome which protrude out of the nucleosome ( One histone core of eight histone subunits and the DNA molecule is wrapped twice around a Histone Octamer is a nucleosome), or between different, neighboring nucleosomes, or even distant ones.

The interplay between such effectors, readers and writers generate a multifaceted network of intertwined contacts that can provide a high degree of specificity. Furthermore, many nuclear complexes are not static and undergo component swapping, a powerful mechanism for altering their chromatin-targeting capabilities. Beyond mediating specific chromatin anchoring, PTM cross-talk can also trigger a cascading series of writing, erasing and reading events.

Access to the DNA within chromatin involves the cooperative action of DNA sequence, site-specific transcription factors, histone modification enzymes, and a set of chromatin remodeling complexes.

These mechanisms activate transcription through transcription factors, which bind on regulatory sequences on the Genome, and start gene expression. Transcription activation depends on six sequential steps, and is EXTREMELY COMPLEX, depending on hundreds of specialized proteins, where, if one is missing or malfunctioning, the result is disease, cancer, and Cell death.

How do secular science papers explain the origin of gene regulatory networks? You can guess - of course - evolution !!

Eugene Koonin: The origin of eukaryotes and multicellularity involved invention of several fundamentally new functional systems. The eukaryotic chromatin remodeling machinery is such a major eukaryotic innovation, which does not appear to have direct prokaryotic predecessors analogs.

Another paper claims:
Nucleosome-remodeling enzymes may thus have evolved directly from ancestral helicase-type motors, and peripheral domains have furnished regulatory capabilities that bias the remodeling reaction toward different structural outcomes.

Coordinated actions, regulation, and strategic interactions are crucial and must be pre-programmed by intelligence and require foreknowledge of distant needs. Were these peripheral domains not precisely structured and specialized to perform the task right from the beginning, they could not perform properly.  Random, unguided non-intelligent natural processes would need to promote a future functional outcome with intermediate non-functional stages, and evolving the right physical properties of these peripheral domains, finely tuned to perform a conjoined co-operative action and correct regulation tasks once the system was fully set up. Furthermore, transcription activation is life-essential and could not occur, if the process was not fully implemented.   Even more, coordination and regulation are required for these biological processes since it indicates that when both are not existent or fully implemented, the life-essential processes like transcription activation cannot occur properly, and in cases of malfunction, causing cancer.

Eugene Koonin attributes its origin to a momentous evolutionary transition. This scenario indicates however rather that a set up through gradual evolutionary mechanisms is not possible. The requirement of fine tuning and extreme regulation of the whole process, its management, and control, certainly require all or almost all the components. 

Davidson gives the death strike: 
No subcircuit functions are redundant with another, and that is why there is always an observable consequence if a dGRN subcircuit is interrupted. Since these consequences are always catastrophically bad, flexibility is minimal, and since the subcircuits are all interconnected, the whole network partakes of the quality that there is only one way for things to work. And indeed the embryos of each species develop in only one way.

"Irreducible complexity has been debunked?


There is no irreducible complexity? I see it ALL OVER in molecular biology. If someone tells you that IC has been debunked, he just signed a declaration of HAVING NO CLUE about the issue.
What emerged first: Gene repression, or activation?
Life would not exist without both...."

Adaptation of cells to new environments

https://reasonandscience.catsboard.com/t2061p125-my-articles#6174

Several life-essential EPIGENETIC mechanisms respond to environmental stress. 

- heat shock factors (HSFs)
- The unfolded protein response (UPR)
- nonhomologous end-joining and homologous recombination
- The DNA Damage Response
- The Response to Oxidative Stress

Evolution takes supposedly thousands of years to gain an environmental advantage. So what environmental benefit would evolution supposedly provide, if adapting and responding to environmental stimuli is not only a life-essential process which had to be fully implemented when life began but, furthermore, a pre-programmed process based on information through signaling networks?


Cells have many mechanisms to modulate the signaling pathways at transcriptional, post-transcriptional and post-translational levels.

Organisms respond to short-term environmental changes by reversibly adjusting their physiology to maximize resource utilization while maintaining structural and genetic integrity by repairing and minimizing damage to cellular infrastructure, thereby balancing innovation with robustness. The cell’s initial response to a stressful stimulus is geared towards helping the cell to defend against and recover from the insult. 2 The fact that the cell’s survival critically depends on the ability to mount an appropriate response towards environmental or intracellular stress stimuli can explain why this reaction is highly conserved in evolution. The adaptive capacity of a cell ultimately determines its fate.

One of the reasons behind the evolutionary success of mammals (and other multicellular organisms) is their extraordinary capacity to adapt to changing environmental conditions. 3

Maybe the author should ask himself, how the Cell could have survived without the mechanism implemented from day one !!

If the stress stimulus does not go beyond a certain threshold, the cell can cope with it by mounting an appropriate protective cellular response, which ensures the cell’s survival. One of the main prosurvival activities of cells, the heat shock response, was originally described as the biochemical response of cells to mild heat stress (i.e., elevations in temperature of C above normal) During initiation of the heat shock response general protein transcription and translation is halted, presumably to alleviate the burden of misfolded proteins in the cell. However, transcription factors that enhance expression of a specific subset of protective genes are selectively activated under these conditions; these are the heat shock factors (HSFs) Vertebrate cells have three different HSFs: HSF1 is essential for the heat shock response and is also required for developmental processes, HSF2 and HSF4 are important for differentiation and development, while HSF3 is only found in avian cells and is probably redundant with HSF1 .

Secretory and membrane proteins undergo posttranslational processing, including glycosylation, disulfide bond formation, correct folding, and oligomerization, in the ER. In order to effectively produce and secrete mature proteins, cellular mechanisms for monitoring the ER environment are essential. Exposure of cells to conditions such as glucose starvation, inhibition of protein glycosylation, disturbance of Ca2+ homeostasis and oxygen deprivation causes accumulation of unfolded proteins in the ER (ER stress) and results in the activation of a well-orchestrated set of pathways during a phenomenon known as the unfolded protein response (UPR)

Upon cellular stress conditions that are caused by exposure to chemotherapeutic agents, irradiation, or environmental genotoxic agents such as polycyclic hydrocarbons or ultraviolet (UV) light, damage to DNA is a common initial event DNA double-strand breaks (DSBs) and single-strand breaks (SSBs) are considered as key lesions that initiate the activation of the DNA damage response. Damage to DNA engages DNA repair processes to ensure the cell’s survival in the case of sublethal damage. Depending on the type of lesion, DNA damage initiates one of several mammalian DNA repair pathways, which eventually restore the continuity of the DNA double strand. There are two main pathways for the repair of DSBs, that is, nonhomologous end-joining and homologous recombination

Cell survival requires appropriate proportions of molecular oxygen and various antioxidants. Reactive products of oxygen are amongst the most potent and omnipresent threats faced by cells. These include ROS such as

superoxide anion
hydrogen peroxide (H2O2)
singlet oxygen
hydroxyl radical (OH•)
peroxy radicals
the second messenger nitric oxide (NO•) which can react with O2 to form peroxynitrite (ONOO−)

Infectious agents can drive a plethora of stress responses by activating pattern recognition receptors. In the initiation of innate immune responses against pathogens, pattern-recognition receptors (PRRs) have an essential role in recognizing specific components of microorganisms and triggering responses that eliminate the invading microorganisms. However, inappropriate activation of PRRs can lead to prolonged inflammation and even to autoimmune and inflammatory diseases. Thus, PRR-triggered responses are regulated through the degradation or translocation of the innate receptors themselves and through the involvement of intracellular regulators or amplifiers. In addition, a complex interplay between PRRs and/or other immune pathways finely tunes the outcome of host immune defense responses. 4

Considerable evidence has now accumulated indicating that the intracellular mechanisms that are activated in response to different stresses — which include the DNA damage response, the unfolded protein response, mitochondrial stress signalling and autophagy — as well as the mechanisms ensuring the proliferative inactivation or elimination of terminally damaged cells — such as cell senescence and regulated cell death — are all coupled with the generation of signals that elicit microenvironmental and/or systemic responses. Such mechanisms of cellular adaptation to stress contribute to the formidable resilience of the organism but can also contribute to its degeneration over time. 3

Normally in cells there exists equilibrium between pro-oxidant species and antioxidant defense mechanisms such as ROS-metabolizing enzymes including catalase, glutathione peroxidase, and superoxide dismutases (SODs) and other antioxidant proteins such as glutathione (GSH)

For the preservation of organismal homeostasis, as severely damaged, irreversibly infected, functionless and/or potentially oncogenic cells are destined for persistent inactivation or elimination, respectively.

It has become apparent that most (if not all) mechanisms of cellular response to stress are also associated with paracrine and endocrine signals that communicate a potential threat to the organism and hence contribute to the maintenance of systemic homeostasis. 


Signaling pathways and regulators of PRRs. 
Pattern-recognition receptors (PRRs) share intracellular pathways that lead to the production of pro-inflammatory cytokines and type I interferons (IFNs). 
a | All the Toll-like receptors (TLRs), except for TLR3, interact with MYD88 to induce the activation of nuclear factor-κB (NF‑κB) and mitogen-activated protein kinases (MAPKs), which induce the transcription factor activator protein 1 (AP-1), for the induction of pro-inflammatory cytokine expression. The TIR domain-containing adaptor protein inducing IFNβ (TRIF) pathway is shared by TLR4 and TLR3, and induces the activation of interferon regulatory factors IRF3–IRF7 for the production of type I IFNs.
b | Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) first interact with mitochondrial antiviral signaling protein (MAVS) and then activate signaling cascades through stimulator of interferon genes (STING) and TANK-binding kinase 1 (TBK1), leading to the expression of type I IFNs. MAVS also signals through receptor-interacting serine/threonine protein kinase 1 (RIPK1) for AP‑1 activation. 
c | Many cytosolic DNA and RNA sensors, including cyclic GMP–AMP synthase (cGAS), double-strand break repair protein MRE11, IFNγ-inducible protein 16 (IFI16), DNA-dependent protein kinase (DNA‑PK), the probable ATP-dependent RNA helicases DDX41 and DDX60, leucine-rich repeat flightless interacting protein 2 (LRRFIP2) and protein kinase RNA-activated (PKR), recognize intracellular DNA or RNA and converge on STING to drive type I IFNs and cytokine production. The ATP-dependent RNA helicases DHX9 and DHX36 recognize CpG-containing DNA and induce the MYD88‑dependent signalling pathway. 
d | NOD-like receptors (NLRs) are activated upon cellular infection or stress, and engage innate immune responses via RIPK2–NF‑κB signalling activation. Some NLRs, such as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), ICE protease-activating factor (IPAF) and NLR apoptosis inhibitory protein 5 (NAIP5), form inflammasomes that contain the apoptosis-associated speck-like protein containing a CARD (ASC) and caspase 1, and trigger the maturation of interleukin-1β (IL-1β). 4


1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081528/
2. https://www.hindawi.com/journals/ijcb/2010/214074/
3. https://www.nature.com/articles/s41580-018-0068-0?subid1=20221026-1100-457b-8630-134ba6da965b
4. https://pubmed.ncbi.nlm.nih.gov/26711677/

Who created God? And how did he create the universe?

One of the most common ways atheists conduct and continue a debate, once they have no escape and every objection of the watchmaker argument has been refuted, is, to move goalposts, and to ask either: Who created God, or how he created the world.  

Question: Would God not cease to be God, if he depended on someone or something else to be God? Is God not the highest being, nothing above him, and as such, the first, or necessary cause?

On an “Anselmian” conception of God, God is the greatest possible being; it is in the very nature of God that he essentially (and necessarily) possess all compossible perfections.

Are these questions not a sign about how philosophically ill-informed many atheists are? And need to be spoon fed 101 on the very basics? unfortunately yes.

Who or what created God?
https://reasonandscience.catsboard.com/t77-who-created-god

The creator is a self-existing power. He is not created; He is eternal.   He is the One who brought time, space, and matter into existence.  Since the concept of causality deals with space, time, and matter, and since God is the one who brought space, time, and matter into existence, the concept of causality does not apply to God since it is something related to the reality of space, time, and matter.  The cause of the universe must have been non-material because if the cause was material/natural, it would be subject to the same laws of decay as the universe. That means it would have to have had a beginning itself and you have the same problem as cycles of births and deaths of universes. So the cause of the universe’s beginning must have been supernatural, i.e. non-material or spirit—a cause outside of space-matter-time. Such a cause would not be subject to the law of decay and so would not have a beginning. That is, the cause had to be an eternal spirit.

5 Easy Steps to refute naturalism
https://reasonandscience.catsboard.com/t1877-easy-steps-to-refute-naturalism

Either the cosmos
(1) had no beginning, or
(2) it had a beginning.
(1) If the cosmos had no beginning, then there must be an infinite series of past events. However, it is impossible to traverse an actual infinite. Therefore, the universe cannot be infinitely old. Besides that, If the cosmos was infinitely old, it would have reached maximum entropy a long, long, time ago. Since it has not reached maximum entropy, it cannot be infinitely old without violating the second law of thermodynamics.
(2) If the cosmos had a beginning, then it must have come from (A) nothing or (B) something.
2.A. Although physicists such as Krauss and Hawking talk about "the universe creating itself from nothing," they are using the word "nothing" to mean the vacuum energy, which is not a true nothing. To be more precise, being cannot emerge from non-being.
2.B. If the entire cosmos came from something, that thing must transcend our cosmos, that is, it must exist beyond the limits of our space/time continuum. We may call it the First Cause.

What's the Mechanism of Intelligent Design?
https://reasonandscience.catsboard.com/t1794-how-exactly-did-god-create-the-universe-and-the-world-what-process-was-involvedwas-involved

We don't know how exactly a mind might can act in the world to cause change. Your mind, mediated by your brain, sends signals to your arm, hand and fingers,  and writes a text through the keyboard of the computer  I sit here typing. I cannot explain to you how exactly this process functions, but we know, it happens. Consciousness can interact with the physical world and cause change. But how exactly that happens, we don't know. Why then should we expect to know how God created the universe? The theory of intelligent design proposes an intelligent mental cause as origin of the physical world. Nothing else.  

An intelligent designer creates through power, information input ( words ), wisdom, and will. But how exactly does this work?

Ann Gauger: It's still worth considering how a mind might act in the world to cause change. The answer is we don't know. I sit here typing. My mind, mediated by my brain, is putting words into a computer program (designed by other minds, by the way), using my fingers to type. But how does it happen, really? Where does the impulse to press one key instead of another come from? And how do these words, products of my mind, communicate to others through their computer screens? We can't really say how our own minds work to interact with the world, yet we know they do. It is our universal, repeated, personal experience that shows us that our consciousness interacts with our bodies to produce information, but exactly how it works is not known. So why should we expect to know how the agent(s) responsible for the design of life or the universe may have worked? The theory of intelligent design does not propose a mechanism (a strictly or necessarily materialistic cause) for the origin of biological information. Rather, it proposes an intelligent or mental cause. In so doing, it does exactly what we want a good historical scientific theory to do. It proposes a cause that is known from our uniform and repeated experience (to borrow a phrase) to have the power to produce the effect in question, which in this case, is functional information in living systems.

Some reasons why life is an all or nothing process

Availability of some of the basic building blocks for life
Each of the following global energy Cycles are essential for advanced life on earth: the Water Cycle, Carbon Cycle, Nitrogen Cycle, Global Carbon Cycle, Phosphorus, Iron, and Trace Mineral cycles. They are also interdependent with each other. Which came first?

Nitrogen is essential for the make of nucleic acids and proteins—the two most important building blocks of life. The availability of nitrogen in the form of ammonia which microorganisms can uptake,  to produce DNA and amino acids, depends on the nitrogen cycle. But the nitrogen cycle depends on cooperating microorganisms, operating in a coordinated manner, which promotes a fine ecological cycle balance. These microorganisms could not emerge without DNA and nucleic acids.
What emerged first: DNA and nucleic acids to make these microorganisms, essential for the nitrogen cycle, or the Nitrogen cycle, essential for the production of these building blocks, making the origin of micro-organisms possible?
 
The carbon dioxide level in the atmosphere must be just right: If greater: runaway greenhouse effect would develop.  If less: plants would be unable to maintain efficient photosynthesis

Carbon has unique properties that make it the backbone of all organic compounds. Carbon must be made bioavailable through carbon dioxide fixation which depends on specialized enzymes that perform the task. In all living organisms, the central metabolic pathways promote the sugar-phosphate reactions which provide the precursor building blocks required for the make of RNA, DNA, lipids, energy, and redox coenzymes and amino acids—key molecules required for life. No non-enzymatic pathways to fix Carbon dioxide were likely responsible on early earth ( they would likely have disintegrated with UV radiation ). It takes enzymes to make the precursor building blocks of life. But it requires the precursor building blocks of life to make the key molecules, required to make enzymes which fix carbon. What came first?

Adaptation of life to the environment - essential for life
The ability to change over time in response to the environment is fundamental and is determined by the organism's genetics, its gene regulatory network, and modulation of the signaling pathways at transcriptional, post-transcriptional and post-translational levels. At least five life-essential signaling networks dependent on preprogrammed intracellular information transmission systems respond to environmental stress. How could the first living Cell have survived without the mechanism implemented from day one?

Reproduction is essential for the survival of all living things.
Reproduction is essential for the survival of all living things and depends on DNA replication, which involves more than thirty specialized proteins. Each essential for the task. It takes proteins to make DNA replication happen. But it takes the DNA replication process to make proteins. What came first?

The gene regulatory network:
What emerged first: Gene repression, or activation? Life would not exist without both....

What emerged first, genetic, or epigenetic information? Genetic information could not be expressed at the right time in the right place without the epigenetic information, when and where to do so.

Proteins and Catch22
Which came first, proteins or protein synthesis? If proteins are needed to make proteins, how did the whole thing start?" The end result of protein synthesis is required before it can begin.

Protein machines are needed to read the DNA, but these protein machines are themselves made upon the instructional blueprint stored in DNA.

The transition from RNA to DNA depends on Ribonucleotide reductase proteins. The make of proteins depends on the instructions from the instructional blueprint, stored in DNA.
DNA is required to make Ribonucleotide reductase proteins. But these proteins are required to make DNA. What came first?

Lipid Membranes
The Lipid membrane would be useless without membrane proteins but how could membrane proteins have emerged in the absence of functional membranes?

A living cell requires a protective lipid membrane, and a huge number of various types of life-essential membrane proteins, like proton pumps, receptor proteins, anchor proteins, channel proteins, transmembrane proteins, carrier proteins etc.  Lipid membrane and Membrane protein synthesis occur inside living Cells, protected by the Cell membrane, and a homeostatic milieu. Membrane protein synthesis depends on the ordered organized import of the basic building blocks to make them.  What emerged first, Cell membranes and membrane proteins, or their synthesis, if its synthesis depends on both?

Metabolic pathways
The central metabolic pathways like glycolysis or the Citric Acid cycle are essential to make Adenine triphosphate ( ATP ),  the energy currency in the cell, and amino acids, the basic building blocks of proteins. These metabolic pathways use enzymes, which are made through ATP and amino acids. How did these pathways emerge?

Metabolism, or replicator, what came first?
Both metabolism and replication are complementary processes. RNA is claimed to be the information carrier prior to DNA on early earth, and a catalyst at the same time. How could it have been so, without energy supply depending on metabolism?

Error check and repair
There are elaborate surveillance mechanisms, DNA and RNA quality control, and repair systems. The DNA and protein error check and repair system would have needed to be there from the beginning. What came first, RNA or DNA replication, or quality control, error check and repair mechanisms?

What came first, the software, or the hardware in the Cell ?
DNA is an information storage system like a hard disk of a computer and stores algorithmic (instructional) information.  What emerged first, the DNA molecule which equals to the hardware, or the blueprint stored through DNA, which equals a software? There is no reason for information processing machinery to exist without the software and vice versa.

RNA nor DNA outside of a living cell has no function, no purpose. To exercise its task, DNA must be part of a large factory-like production line, with each compartment exercising its specific purpose alongside the others in a cooperative manner, where one compartment depends on the product of another. That raises an insurmountable hurdle for unguided processes in early earth. If biochemical processes inside living cells only result in purposeful outcomes, if interconnected and interdependent like in a factory assembly line, how did the individual specific parts emerge, if they have no function by their own ?

The vast complexity of millions of proteins species in Human Cells made through alternative splicing of genes by an epigenetic splicing Code point to design

The vast complexity of millions of proteins species in Human Cells made through alternative splicing of genes by an epigenetic splicing Code point to design

Results of early scientific research proposed that the outcome of one gene was responsible for the synthesis of one type of protein. Then, it was discovered, that the protein variation was far higher than the about 20 thousand genes in the human genome. Next, it was discovered, that a molecular machine of extraordinary complexity, the spliceosome, was responsible for producing this variety of proteins.

The awe-inspiring spliceosome, the most complex macromolecular machine known, and pre-mRNA processing in eukaryotic cells

https://reasonandscience.catsboard.com/t2180-the-spliceosome-the-splicing-code-and-pre-mrna-processing-in-eukaryotic-cells

The spliceosome edits introns and "cuts" them out of the genome, and keeps exons, through an epigenetic code, called the splicing Code ( how could evolution have produced this Code and language, amongst over a dozen other intracellular codes on top of the Genetic Code, and a signaling network, and used it, to program the right slicing of millions of gene variants, to make millions of various functional protein species eh !!?? )

Even the most advanced supercomputer cannot calculate and predict the right folding of one medium-sized protein !! - but according to the narrative of secular science, mutations and natural selection are capable of the feat - no intelligence required. Really ??

But on top of that, it was discovered that an even more complex process occurs where exons themselves are edited by being cut, reorganized and pasted,

Even more surprising, the cell machinery takes sections from distant, various different genes, and joins them together, to produce further messenger RNA variants !! - how cool is that eh - there can be as much as over 100 gene parts joined together to produce a different protein variant...

Cells are pre-programmed to produce exactly the required protein 3D forms that are functional in over 200 different Cell types in the human body !!

Interestingly, alternative splicing makes our brain unique amongst all other life forms. We have the most complex splicing variants. In neurons in our brain, so-called splicing enhancers and silencers are programmed to determine the exact type of editing that has to go on. That permits the human genome with about 20 thousand genes to produce about 6 million proteins species and variants !!

On top of that, there is another set of regulatory proteins which control, regulate, and assist alternative splicing during brain development !!!

Many different splicing factors interact together in a complex network and crosstalk to produce particular Cell types for their particular functions.

How good is it to be able to exclaim wholeheartedly

Psalm 139.14
I praise you, Lord, because I am fearfully and wonderfully made; your works are wonderful i know that full well.

Electrical Fields Guiding 3D Shape of Cells and Organs

In order to understand what defines CHANGE and/or evolution of an organism, what needs to be known, is what kind of mechanisms generate/define/ specify/inform:

1. Kind or type of cell ( Histology),
2. Cell size
3. Cells specific functions,
4. Position and place in the body. This is crucial. Limbs like legs, fins, eyes etc. must all be placed at the right place.  
5. How cells are interconnected with other cells,
6. Cell-Cell communication and signaling, and setup of the communication channels and signaling language
7. setup of specific sensory and stimuli functions in regard to its environment and surroundings
8. regulatory, fine-tuning, control, repair functions
9. When and which genes will the development program of the gene regulatory network express the right genes to grow the right cell types during development?
11. Precisely how many new cell types, and how many of each, must be produced for each tissue and organ?
10. Specification of the cell-cell adhesion and which ones will be used in each cell to adhere to the neighbor cells ( there are 4 classes )
11. Programming of  time period the cell keeps alive in the body, and when is it time to self-destruct and be replaced by newly produced cells of the same kind
12. Set up its specific nutrition demands
13. How to organize the chromatin and chromosomes, compaction of DNA in the nucleus

The mechanism that forms an organism structure, limbs, organ organization, and above specifications in a multicellular organism, are also the ones that are responsible for organismal change and evolution if they - themselves -  change or mutate.

The traditional view that gene information alone defines body form and structure has been replaced in accordance with new scientific knowledge and more clear picture of the intracellular - molecular landscape that has emerged in the last few decades, and as such, Darwin's theory by itself has evolved, and the new findings have been up to a certain point integrated into the modern neo-Darwinian extended evolutionary synthesis.

The new synthesis tries to incorporate mechanisms at the level of genes, phenotypes, and populations whereas darwins theory was concerned mainly with organisms, speciation, and individuals.

What recent scientific discoveries however demonstrates is, that the reformed view also is outdated. The reality of the molecular world is far more complex, and there is no end in sight to unravel new,  higher levels of complexity. We know today, traits and phenotype are not only depending on genetic information but on a structural level of whole Cells and various epigenetic information systems.

The picture that emerges is, that information permeates and guides everything in molecular biology. There is not only genetic information but over a dozen epigenetic codes, but information is also generated in a dynamic web, and transmitted through signaling by various signaling networks. Electric fields, through the special arrangement and placement of pumps, transporters, ion channels situated within the plasma membrane of each cell type generate patterns of ion gradients which direct many cells- and molecular biological processes such as embryogenesis, wound healing, regeneration, and these electric fields (EF), thereof, produce guiding cues for cell migration and organism development. There are many other mechanisms that orchestrate and define the make of body architecture, but this example alone demonstrates why Darwin's theory of mutations and of allele variation and natural selection is outdated. Other mechanisms like just mentioned electric fields on cell membranes generated through the special arrangement and order of pumps, transporters, ion channels on Cell membranes do generate bioelectrical signals, codified information which directs cell migration under the guiding cue of electric fields , and a disruption of this information cascade during development, e.g., by blocking of cell membrane-bound proton transporters, will ultimately lead to malformation, dislocation of organs and other severe defects. 

The question now, of course, is: How could that special arrangement of pumps, transporters, ion channels situated within the plasma membrane be best explained? That arrangement is complex and specifies electric fields that direct Cell migration. In case of the human body, 3,7 trillion Cells !!  Evolution, or design? 

Sadly, Darwin doesn't live today, to learn and to know about all this amazing stuff. Then, probably, his theory would never have taken off.  But you can appreciate it, and draw correct, logical conclusions. Hope you do so.... 

More on this:

The recent groundbreaking scientific research which explains the real mechanisms of biodiversity
https://reasonandscience.catsboard.com/t2293-the-recent-groundbreaking-scientific-research-which-explains-the-real-mechanisms-of-biodiversity

Where Do Complex Organisms Come From?
https://reasonandscience.catsboard.com/t2316-where-do-complex-organisms-come-from

The remarkable modular organization and structure  of gene regulation, higher order control, and gene expression systems in biological Cells 

This article can best be read here:
https://reasonandscience.catsboard.com/t2726-chromatin-remodeling#6186

1. The setup of functional Information retrieval systems, like a library classification system, is always tracked back to intelligence. 
2. The gene regulatory network is a fully automated, pre-programmed gene information extraction system
3. Therefore, its origin is best explained through intelligent setup

Many, if not most complex man-made machines are based on elementary discrete mechanical parts. These elements consist of three basic types:

- structural components such as frame members, bearings, axles, splines, fasteners, seals, and lubricants,
- mechanisms that control movement in various ways such as gear trains, belt or chain drives, linkages, cam and follower systems, including brakes and clutches, and
- control components such as buttons, switches, indicators, sensors, actuators and computer controllers.

Machines can generate energy and change it from one form into the other transfer, increase or decrease forces or change direction, transport cargo, move loads, changing equilibrium states etc.  Molecular motors and machines do all this and are central to almost every biological process.

There is a variety of specialized machine elements such as splines, pins, keys etc. Each of these must be precisely shaped, specified, and require complex shapes and must be made of materials apt to the various tasks ( Thermal resistance, bond formation, elasticity, etc. ). They have to be able to connect like pieces of a puzzle or a lock to its key, and require high specificity, and interact properly fine-tuned with each other, and structurally be complementary.  Structural complementarity is as well a significant functional property of biological systems. The parts must be mutually compatible, that is, ‘well-matched’ and capable of properly ‘interacting’: even if subsystems or parts are put together in the right order, they also need to interface correctly. Complex machines must be built in the right way and the machine elements must be assembled in the right sequence. The majority of ways of assembling them will be non-functional or irrelevant.  

There must be specific goals and knowledge of the end purpose of a machine. Only artists make purposeless machines for the sake of aesthetics ( and even that is a goal ) 

To make machines, following is required:

- selection of the right basic materials and to purify, and bring together in the right quantity to the same assembly and manufacturing site
- making the individual elements
- join them together in the right sequential order to get a functional machine
- manage energy supply to the specific sites

Further complexity is involved, if the machine requires inbuild pre-programmed quality control, error check and repair mechanisms, full automation, the ability to adapt to different surrounding conditions, oscillation and variation of energy supply, or supply shortage or surplus management of the basic building blocks.   

Now imagine, this machine is a fully automated robot, a part of an assembly line, where 10 robots, each one preprogrammed through a computer,  assigned to its specific task, process the intermediate production stage of another machine part with entirely other purposes. Each intermediate product has no function by its own. The pathway must go all the way through, all 10 steps, otherwise, that machine element will not functional, and cannot be employed in that much larger system.  That machine element, by its own, has no function, but as well, is useful only in the completion of that much larger system.

Latest here, Darwin's theory brakes down, since there has to be an improvement of function or adaptation, but intermediate, non-functional products have no purpose, and evolution has no distant goals.

In biology, the genome stores the information to build molecular machines ( We can compare a gene to a book or blueprint ).  

Imagine a library with various sections. 

One section contains books that inform how to make the basic building blocks of life.  One book containing the information to make DNA nucleotides. Another, how to make amino acids, Another, hydrocarbons, another, fatty acids. 
In another section of the library, there are books about molecular information, Software and hardware systems, the gene regulatory network ( Chromatin, nucleosomes, DNA methylation)  information retrieval ( RNA polymerase ) in other books,  transmission systems ( messenger RNA ) and  translation ( Ribosome ), signaling ( hormones )
In another section of the library, there are books about how to build millions of different complex machines ( proteins ), another  factory assembly lines ( fatty acid synthase, non ribosomal peptide synthase ), error check and repair systems  ( exonucleolytic proofreading, strand-directed mismatch repair ) , recycling methods ( endocytic recycling ), waste grinders and management  ( Proteasome Garbage Grinders )  , power generating plants ( mitochondria ), power turbines ( ATP synthase ), and electric circuits ( the metabolic network ).

In the human genome, there are about 20 thousand genes, divided in 23 chromosomes. Imagine, each gene equals a book with the informational blueprint to build the molecular systems described above. The human chromosome has about 2 meters of length.  In its most condensed state during mitosis, the chromosome is about 2 µm long. This gives a packing ratio of 10.000. To fit 2 meters of DNA into a tiny nucleus is a monumental engineering feat. To achieve the overall packing ratio, DNA is not packaged directly into the final structure of chromatin. Instead, it contains several hierarchies of organization. The first level of packing is achieved by the winding of DNA around a protein core to produce a "bead-like" structure, the nucleosome. The shape of the chromatin, down to histone organization, determines function, with new secondary and tertiary structures which organize gene expression. 

Imagine a self-driving car. Even today, the programming of self-driving cars that are secure enough on the street are not market ready. The amount of information processing required to direct a car from A to B on a highway is monumental. And to develop a software which is able to direct cars autonomously is a truly an extraordinary feat, which has required up to know thousands of highly skilled software engineers to develop these software programs. But the program alone is not enough. The car itself must be interface compatible to interpret the information input from and direction from the program and transmit it to the wheels etc. Up to now, the human brain does what humans try to delegate to autonomous cars. 

The human brain is loaded daily with 34 GB of information
The average human brain processes daily over 100 thousand words, that is such a large volume of information which could overload even a powerful computer, according to a new U.S. scientific research. 2

Each biological Cell is faced with the challenge to find the right information in the nucleus. In humans Cells, amongst strings of 3 billion nucleotides. 

If someone wants to find a book in a library, the information is required in which shelf the book is stored, and the title of the book, clearly recognizable. Following is needed to get the book and use its information content: 

- Information which directs to the book in the shelf
- A way to go to the shelf, take the book out of the shelf, transport it to the appropriate place where it can be read, copied, may be translated ( if required ), send the information to the manufacturing site, where the information/blueprint is used  to actually build the device described in the book, close the book, and bring it back to the shelf, and store it at the same place. That way, the information is again at disposal, when required next time. Humans require a lot of sensory devices ( vision, ears ) and information, and transform it in physical activity, by using legs to  walk to the shelf, recognize the book, use the arms, hands, and fingers, to take the book out of the shelf, transport the book to the copy department, send the copied information to the factory, and then return the book to the library, and put it back to the right place on the shelf. 

Cells need to perform the same task. Science does however not know yet precisely, how the gene regulatory network manages it. But it happens, fully pre-programmed, autonomously, and with high precision and control. And under various ecological conditions, nutrition supply, and ontology as well.  The molecular machinery that performs all this is nothing short than amazing and awe-inspiring.

To exemplify and illustrate, let's give a closer look to Chromatin Remodellers. Access to the DNA within chromatin involves the cooperative action of DNA sequence, site-specific transcription factors, histone modification enzymes, and a set of chromatin remodeling complexes. The wrapping of DNA into nucleosomes contributes to transcriptional repression, as nucleosomes inhibit the binding of transcription factors and the progress of RNA polymerases. Therefore, transcriptional activation often requires the repositioning or ejection of repressive nucleosomes. These activities are performed by large multiprotein complexes termed remodelers, which are grouped into five classes.  They are true multitask performers. They help in DNA replication, DNA repair through many different types of remodelers, Transcription regulation ( they either block or clear promoters that activate the transcription machinery ), and regulation of chromosome structure.

While a book is just laid down on a shelf ( and kept there by gravity ) nucleosomes use far more sophisticated mechanisms. 

The interface between DNA and histone is extensive: 142 hydrogen bonds are formed between DNA and the histone core in each nucleosome. Nearly half of these bonds form between the amino acid backbone of the histones and the phosphodiester backbone of the DNA.  More than one-fifth of the amino acids in each of the core histones are either lysine or arginine (two amino acids with basic side chains), and their positive charges can effectively neutralize the negatively charged DNA backbone. These numerous interactions explain in part why DNA of virtually any sequence can be bound on a histone octamer core. The sequence preference of nucleosomes must be weak enough to allow other factors to dominate, inasmuch as nucleosomes can occupy any one of a number of positions relative to the DNA sequence in most chromosomal regions.

What would happen if the net charge of histones would not neutralize the charge of the DNA backbone? DNA would bind in such a strong manner, that other factors would be unable to unwind the DNA, it could not be read, and effectively, the Cell would die. How could and would evolution find in a vast sequence space the right amino acids, providing the forces that permit the unwinding? Trial and error? Each time, it would try a sequence which is non-functional, the Cell would die. That makes the proposal of evolution as extremely unlikely. The histones had to be fully operational right from the beginning, what demonstrates that design is a far better and more case-adequate explanation rather than nonguided selective forces of evolution. 

Nucleosomes must dynamically change so that DNA binding complexes can access their binding sites. These dynamic changes, which include nucleosome unwrapping, rewrapping, sliding, assembly, and disassembly, involve the formation and/or disruption of interactions within the interfaces between the DNA, H3/H4, and H2A/H2B components of the nucleosome.  ATP-dependent chromatin remodelling complexes, which use the energy of ATP hydrolysis, locally disrupt or alter the association of histones with DNA.

That equals to take a book out of the shelf. Then, transcription factors gain access to the DNA molecule, recognize and bind to the promoter region in DNA, and recruit the RNA polymerase machinery to start its job.

The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Mutations in BAF complex subunits are linked to neurodevelopmental disorders, like schizophrenia - amongst many others.  Mammalian neural structures are functionally made up of neural cells that develop under strict molecular and cellular instructions to confer cell subtype differentiation.  Highly ordered gene expression programs regulate the establishment of various cell fate status during neural development. Many factors, including epigenetic and chromatin regulators, act in concert to determine and sustain cell-specific transcriptional programs.

How did Chromatin remodellers emerge? Evolution, or design? If they were not there right from the beginning, the complex chromatin organization in eukaryotic Cells could not be there. 

1. http://dev.biologists.org/content/143/16/2882
2. https://www.tech21century.com/the-human-brain-is-loaded-daily-with-34-gb-of-information/

God is good

God, in his infinite power, wisdom, and intelligence had probably no difficulty to fathom, visualize, imagine, project, create and implement the physical universe, and life. Christ was not boasting about his power and intelligence, despite being the most intelligent, powerful,  and wise man that ever walked on the face of the earth. When his disciples asked him about the future, and difficult things, he simply said in

John 16.12: I have much more to say to you, more than you can now bear.

He could have said how proteins are formed. He could have said about anything since as author of everything, he knew about everything. Simply put God the father / Christ - God the son / and God the holy spirit /  know everything that can be possibly known. There is nothing, that can be known, that he does not know. But he demonstrated incredible humility and despite being God, superior of all, he humiliated himself to become one of us.

Isaiah 40:13-14
“Who can fathom the Spirit of the LORD, or instruct the LORD as his counselor? Whom did the LORD consult to enlighten him, and who taught him the right way? Who was it that taught him knowledge, or showed him the path of understanding?”

But becoming a sacrifice on the Cross for us to redeem us from our condition of lost sinners, was more difficult, than any difficulty that any human being will ever face on earth. He did sweat blood in Gethsemane, and, while living in close relationship with the father prior and during his life on earth, the father turned his face from him, while he was hanging on the cross. There was a total separation. His screaming was a sign ot total despair:

Matthew 27:46 & Mark 15:34 My God, My God, why have you forsaken me?

The same experience is which all lost and unbelievers and God-deniers will experience when they die, and go to hell. Today, everyone, even unbelievers, experience Gods goodness, even if they do not acknowledge it.

But the sensation of lostness and separation was a moment of total despair, far worse than the physical pain Christ was experiencing. If it was not difficult to create the universe, the earth, and life, it was excruciatingly difficult for the Lord to go through this. Experiencing the separation from the father.

And he did it for you. For me. For every one of us. Nobody of us deserved such grace, love, and being forgiven. We all deserve hell. If HE deserves our admiration for his wisdom, power, and intelligence, HE deserves our love from all our heart and in all our power and possibilities, because he is GOOD and demonstrated how much he loves us in a way that demonstrates Gods power for us, as written:

1 Corinthians 1:18-2:16
For the [a]message of the cross is foolishness to those who are perishing, but to us who are being saved, it is the power of God. For it is written: “I will destroy the wisdom of the wise,
And bring to nothing the understanding of the prudent.”

Exodus 34:6-7a
“The LORD passed before him and proclaimed, “The LORD, the LORD, a God merciful and gracious, slow to anger, and abounding in steadfast love and faithfulness, keeping steadfast love for thousands, forgiving iniquity and transgression and sin.”

Matthew 7:11
“If you then, who are evil, know how to give good gifts to your children, how much more will your Father who is in heaven give good things to those who ask him!”

Exodus 33:19
“And he said, “I will make all my goodness pass before you and will proclaim before you my name ‘The LORD.’ And I will be gracious to whom I will be gracious, and will show mercy on whom I will show mercy.”

2 Chronicles 30:9
The LORD your God is gracious and merciful and will not turn away his face from you if you return to him.”

Various multi-task protein complexes working through conjoined cross-talk point to a designed set-up

As it is crystallizing, the orchestration of Gene expression depends on many different actors. These actors regulate and control which genes have to be either activated or repressed through teamwork and crosstalk and by sharing and processing a multitude of information and signal input. Gene expression is not a static process, but dynamic, depending on ecological conditions, availability of food, and ontology, through signaling cascades triggered by membrane proteins, and from the exterior of Cells.

What is however remarkable is, that various protein complexes involved in gene expression are not responsible just for one task, but several. Chromatin remodelers of the  ISWI  family are involved in DNA replication, DNA repair, Transcription regulation, and Chromosome structure. They are crucial in regulating gene expression by controlling chromatin dynamics and complex, multicellular life could not exist without just these proteins.

Another amazing family of proteins are condensins, cohesins, and Smc5/6 proteins, which spatially organize chromosomes by extruding DNA into large loops. They provide an active DNA loop extrusion and a universal unifying principle for genome organization. Members of the structural maintenance of chromosomes protein family (SMC), including condensin, cohesin, and the Smc5/6 complex, play vital roles in restructuring genomes during the cellular life cycle. Cohesin and condensin complexes are essential for defining the topology of chromosomes through the cell cycle. Condensin plays crucial roles in chromosome organization and compaction. It is a molecular motor traveling an average distance of ≥10 kilobases at a velocity of ~60 base pairs per second. The finding that condensin is a mechanochemical motor has important implications for understanding the mechanisms of chromosome organization and condensation.

As if that were not already amazing enough, these proteins have also several other functions. These (SMC) complexes are central regulators of chromosome dynamics and control sister chromatid cohesion, chromosome condensation, DNA replication, DNA repair and transcription. Cohesin facilitates repair by homologous recombination, influences transcription rates and promotes chromosome condensation. The Smc5/6 complex not only functions in recombination but also facilitates replication and influences the organization of mitotic chromosomes. This broad repertoire of functions is comparable to that of histones.

Condensin produces “super coils” of DNA, one of many steps in packing the delicate DNA strands into a hierarchy of coils that results in a densely-packed chromosome. They are multisubunit protein complexes that play a fundamental role in the structural and functional organization of chromosomes in the three domains of life. The spatial organization of chromosomes is of paramount importance to cell biology. Cohesin is crucial for chromatid cohesion, which is consistent with cohesin having an intermolecular linker function. By holding the two sister chromatids together from their formation during replication until their separation in anaphase, cohesin creates a counterforce to the pulling of the mitotic spindle, which allows correct chromosome alignment and segregation.

My comment: The making of a movie does depend on several teams working together. And many of them do have more than one task and function. And if one of the teams gets sick or cannot be on the set, the whole make of a movie cannot proceed. All other teams have to wait until everybody is on set.

Maybe you remember an episode in 2016, when Johnny Depp was not showing up on the set of  Pirates Of The Caribbean in Australia ( fighting with his (ex)-wife was more important ) They had to wait for him, until they could go on with filming.

In the complex intramolecular world of Cells, if one team of actors is not there, nothing else goes either. If Chromatin remodelers were not there, no complex life. If no Condensin, no correct chromosome alignment, and segregation - no perpetuation of life. Without these machines, the cell could not divide. Condensin is able to introduce positive supercoils into DNA
Can we live without them?  No!  Loss of any single SMC protein is lethal.  

Life is an all or nothing business. And that ALL, so the evidence is demonstrating, means, MANY thousands of protein complexes are absolutely essential, and vindicate more and more the claim that life is irreducibly complex, designed, and not due to slow evolutionary mechanisms.

The pyramid-like hierarchical organization of complex multicellular life-forms points to design

https://reasonandscience.catsboard.com/t2061p125-my-articles#6193

The setup of hierarchical levels of organization, where the function and proper set up of the higher level depends on the lower level, has always been observed to be due to intelligent planning, setup, and design. The same is true for the setup of wiring diagrams in an electrical engineering blueprint or a schematic of an integrated circuit. The genomic program of development demonstrates a multilayered, hierarchical,network-like architecture based on nodes and modules, orchestrating a specific pattern of gene expression. The fundamental role of upper-level Gene regulatory networks is to set up in embryonic space a progressive series of regulatory states, which functionally define first the regions of the body with respect to its axes; then the location of the progenitor fields of the body parts; then the subparts of each body part. Each dGRN module is controlled to be expressed at the right time, and as such, little if no variation is possible. It constitutes an interlocked system. GRNs are logic maps that constrain, orient and direct in detail each module in the lower hierarchy level so that a given gene is expressed at a given time and place. The tight functional constraints under which these systems of dGRNs operate result in catastrophic consequences if altered by mutation and selection mechanisms.


The setup of distant specific goals is always something done by intelligence ( teleology ). Modern biological sciences try to avoid teleology at all cost ( Not an easy task - and often not successfully )

Molecules, basic building blocks of life, proteins, cell compartments, organelles, and organs have often ONLY and EXCLUSIVELY function when employed as a part and ingredient in a complex organizational biological system. But that functional complexity is only achieved by building up lower levels of complexity, which contributes to that higher order and purpose. Therefore, their origin cannot be explained by gradual Darwinian evolution, which depends on slow improvement and positive functionality and fitness on each evolutionary step over a long period of time.

An essential ingredient for biology, to be biology is the implementation of codes and rules of languages, and use of them to codify, complex specified ( instructing ) information like blueprints.

Codified Information has ALWAYS been observed to have only mental, intelligent origin. No exceptions.

An industry usually consists of various factories and several buildings, where manufacturing of goods and machine operating takes place, processing and producing various artifacts. At the beginning of the construction of a factory, there is always a plan, the conceptualization, and a set of specific goals of purposes ( What has to be made ? ).  

The first step of an industry implementation is the elaboration of a master plan, general blueprint and description memorial of the factories, and considerations of where to build the industrial complex. In order for this to happen, there must be a pre-existing language of common agreement amongst all involved in the project. The engineers, computer specialists, administrators etc. must be able to communicate in the same language amongst themselves, and a language which the factory workers do understand, in order to receive the instructions and implement them. If they are in another country with another language, there has to be a translation of the information. 

There has to be a general layout of the factory with information of the various compartments, and how they are interconnected, and interact with each other. Where the raw materials get in, where processed, and where the finished products go out. There have to be roads that lead to the factory, and out to the final destination of the products. 

Then, there have to be layouts of the discrete individual factory compartments, furthermore a detailed description of all assembly and production lines of each compartment, and how to implement and interconnect them.

Then, there have to be descriptions of each individual machine or/and robots and if they are to perform alone, or in a teamwork interconnected with each other ( they may communicate through long-distance information transmission, and be distant and apart from each other), or making part of a physically interconnected assembly line.

Each machine/robot has to be made upon precise specifications of its individual elements and parts; the correct materials, and the import, purification, and transformation of the raw materials into the right useful ones that can and will be employed in the manufacturing process.

And a blueprint and instruction how to build the subelements together, where each part belongs, how they are interconnected, and the right order of assembly too.  

There has to be a conceptualization of how to implement advanced statistical methods of quality control, error check, repair, and waste product disposals, and recycling systems.

The implementation of full automation of these tasks adds a huge amount of complexity; the ability to adapt to different supply conditions, too. How does the factory adapt, if basic material supply shrinks, stops, or sort them out when too many materials become available?  How to generate energy which drives the whole factory, and each machine moving part needs the precise supply of energy, that is another important task of conceptualization. Oscillation and variation of energy supply have to be taken into consideration, too. As it happens, biological machines have sophisticated energy production and supply inbuilt.

It takes complex machines to make energy in the form of  ATP. But it takes energy to make these protein machines that make ATP energy - molecules, the energy currency of the Cell. What came first?  

Let's remember. I just described what blueprints must inform, before beginning with the actual implementation.

There is a hierarchy top/down. In biology, there is a modular gene organization like a pyramid, similar to the description above ( modules that inform the make of the factory as a whole, assembly sequence and development, compartments, machine, machine elements, raw materials, raw material processing and purification, raw material import ) There are modules which describe how to make individual molecules. Other modules describe how to make individual protein subparts. Others how to join them together to functional machines. Others how to interconnect them. Other modules organize the make of organs ( compartments in our factory analogy ) others the organization of these compartments, and how to interconnect them. And on the top of the pyramid is the master plan.

Question: How did that organization emerge? Nature magazine admits:

" There has been no formal demonstration of the adaptive origin of any genetic network. The mechanisms by which genetic networks become established evolutionarily are far from clear. ".

Obviously. That organization has to be planned and conceptualized before implemented, and cannot originate without intelligence.

If you change the blueprint on top of the pyramid accidentally, catastrophic failure is the outcome. That is because that is the place where the information of development of the whole organism is stored, and if you change that part, the whole organismal organization goes havoc.

Paul Nelson:
" So you have this paradox. Hence you have this Darwinian paradox: In order to macro-evolve a species, if you will, you need to have early acting viable mutations. Thow those are the ones that are by far the most destructive. Which means that natural selection cannot operate. Natural selection is a natural process, it is powerless to effect macro-evolution because the kind of variation that it needs is too destructive to animals."

The underlying mechanism is the localized expression of genes ( extraction of genetic information stored in the hard disk of life, DNA ) through specific, so-called transcription factors, which are proteins, that bind at specific pre-programmed time at loci on the genome, directing the transcription machinery to that place to start transcription. ( There has to be also life-essential information which instructs the repression of gene expression which information is not required at that particular moment.) 

Both, gene activation and repression must be implemented from the first go, or nothing goes. How did that happen gradually? It's not possible. 

Of course, the description of all this generates an enormous quantity of information. Which has to be organized and stored somewhere. Today, Computers do the storage. In human factories, the engineers usually instruct the factory workers, either personally, or by sending computer files by email etc. on how to build the machines and factories. But if there is a large number of blueprints, there has to be known where at what place to find the blueprints for each individual and specific device.

A higher, or more demanding, way is to implement a system where the information retrieval system, and then the moving forward of that information to the factory workers,  is fully automated and pre-programmed. That is, rather than engineers go, search for the blueprints at due time and send them to the factory, they implement a program, which does this fully automated. The gene regulatory network in biological Cells does precisely that with mastery, perfect automation, and inbuild control mechanisms which supervise the whole process, and elegant class.

Then, systems of information encoding/transcription, transmission, eventually translation, retrieval, and implementation have to be implemented.  It is evident, that only intelligence can do all this.  

Imagine one of the machines in the factory is a fully automated robot, a part of an assembly line, where 10 robots, each one preprogrammed,  assigned to its specific task, process the intermediate production stage of another machine element with entirely other purposes. Each intermediate product has no function by its own. The production pathway must go all the way through, all 10 steps, otherwise, that machine element will not be functional, and cannot be employed in that much larger system.  

Latest here, Darwin's theory brakes down. The claim that sequential, small evolutionary steps improve a biological system finds its refutation by considering the beforementioned situation.  Since there has to be an increase of adaptation and better function, but intermediate, non-functional products have no purpose, and evolution has no distant goals, mindless evolution by mindless natural selection is not a capable potent mechanism to visualize the overarching aspect of the situation.

Of course, if each individual intermediate machine element had another purpose, somewhere else, it could be co-opted. But to do so, there would still have to be all the specification of where to take it from, how to import it, how to employ it, where to insert it, interface compatibility with other structurally complementary elements, correct size etc. Knowledge would be required for that, which mindless evolutionary processes lack of. And if in a big system just one intermediate part is missing, the whole manufacturing process breaks down and stops.

- No topoisomerase II or helicase proteins, no DNA replication - no life perpetuation.
- No peripheral stalk, a subunit in ATP synthase nano turbines, no energy supply trough ATP for biological cells, no advanced life.


The list is large, and there are thousands of life-essential parts in biological Cells, which makes cells giant irreducible complex systems. 

Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system. In other words: Why would natural selection select an intermediate biosynthesis product, which has by its own no use for the organism, unless that product keeps going through all necessary steps, up to the point to be ready to be assembled in a larger system?
A picture emerges which demonstrates that information is a central player on all stages, both, to make manmade factories, and so, even more, biological Cell factories, and that makes for a rational conclusion that intelligence was involved to create life and biodiversity.

Biological Cells are not factories in an allegorical sense, in a figurative way, in a comparative manner, but they are literally, by all means, factories, which produce almost identical copies of themselves. They are fully automated, pre-programmed to make almost identical copies of themselves. A minimal complexity of life-essential parts had to be there, all at once, to give life a "kick-start". 

While a single protein has no use, no service by its own, but only, when integrated and interconnected with other proteins, often in a production line-like arrangement, making complex molecules, but these molecules by themselves also having no function, unless employed in a higher order to fulfill distant goals, to make for example a self-replicating Cell, such cell, like a specialized blood Cell, has no function by its own, too.  So there is further, higher order and even further distant goals in multicellular organisms. A red blood cell requires another ten life essential different blood cells, each with its precise purpose, in order for blood to become functional.  If one of these blood Cells are missing, blood cannot exercise its function: Natural killer cells, T cells, B cells, Dendritic cells,  Macrophages, Neutrophils,   Basophils,  Red blood cells, and Platelets. Each is necessary. One missing, nothing goes.  But what good is blood for, if there is no multicellular organism? A heart has no use by its own, neither veins nor blood. A circulatory system has no function, unless all other organs are in place, and work in an interdependent manner together.
The Cardiovascular and Respiratory System, Digestive and Excretory System, Endocrine and Immune System, Integumentary and Nervous Systems, Skeletal and Muscular Systems, they work all in an integrated fashion. One has no function without the other.

Irreducible complexity and interdependence in life have been debunked? When? Where? It is actually the opposite way around. It is confirmed. More and more. What has been debunked, is Darwin's theory of mindless goal and purpose-lacking evolution. An essential ingredient for biology to be biology is codified information. And information has ALWAYS mental, intelligent origin.

Darwin and Teleology
https://reasonandscience.catsboard.com/t2606-darwin-and-teleology

The existence of irreducible interdependent structures in biology is an undeniable fact
https://reasonandscience.catsboard.com/t1468-the-existence-of-irreducible-interdependent-structures-in-biology-is-an-undeniable-fact

Main topics on complex, specified/instructional coded information in biochemical systems and life
https://reasonandscience.catsboard.com/t2625-main-topics-on-complex-specified-instructional-coded-information-in-biochemical-systems-and-life

Wanna Build a Cell? A DVD Player Might Be Easier
https://reasonandscience.catsboard.com/t2404-wanna-build-a-cell-a-dvd-player-might-be-easier

Structural Organization of the Human Body
https://reasonandscience.catsboard.com/t2595-structural-organization-of-the-human-body

Control of Gene Expression, and gene regulatory networks  point to intelligent design
https://reasonandscience.catsboard.com/t2194-control-of-gene-expression-and-gene-regulatory-networks-point-to-intelligent-design

Hematopoiesis. The mystery of blood Cell and vascular Formation
https://reasonandscience.catsboard.com/t2295-hematopoiesis-the-mystery-of-blood-cell-and-vascular-formation

If evolution were true, we would rarely die, and limbs of most, if not all living beings would regrow and completely heal
Since evolution is about the survival of the fittest, why are we not all living eternally? According to Dawkins, genes are selfish. They don't care to make and give place to younger generations. Why did evolution not find a way to regenerate somatic cells which get damaged, and why did it not find a way to eliminate cancer once for all? Naked mole has amazing, particularly awesome mechanisms that completely protect them against cancer. We have a whole set of genes that are exclusively dedicated to keeping genes well and fine. A whole armada of repair mechanisms. It repairs genes, proteins freshly produced in ribosomes, chaperones care and bring proteins right to shape to be fit to do their job. Why do salamanders and Jellyfish regrow their limbs, and we don't? It would be a heck of a survival advantage. Actually, the most powerful argument of the Darwinist camp. Sorry guys, it's not the case.....keeping Darwin's ideas is not as easy as that! So evolution has not been capable of fixing these problems for us !! What the heck, is evolution and time not supposed to be our almost omnipotent hero on the block, and Darwin his prophet ??!! Is evolution not our genes friend, putting them straight and direct them to become more complex over time, and solving all problems of ecology and survival? What a pity...... sniff sniff -- Ok, admittedly, accidents happen, we can crash our car and die, and animals are being eaten by others in the food chain ( anyway, could evolution not have been more kind to animals, and not permitted carnivorans to emerge ??!! ) Sorry, Darwin, Dawkins, PZMyers, Coyne et al.... evolution, your hero is not a good answer to these questions. So next time an atheist asks you: Why does God not heal amputees, you can ask him: Why does evolution not learn all organisms to heal amputees?!!
Once more, the bible is the better answer. Read Genesis !!

What defines body structures and architecture?

More of the REAL, really amazing and awe-inspiring, and hardly predicted  mechanisms that define body form and development, which refute an evolutionarily - gene-centred view

you can read this article better here:
What defines body structures and architecture?
https://reasonandscience.catsboard.com/t2590p25-origins-what-cause-explains-best-our-existence-and-why#6161

To understand if the major trends in animal diversity and if the various kinds of morphology are due to evolution, it must first be understood how animal form is generated.

Gene expression patterns cannot explain the development of the precise geometry of an organism and its parts in space.

Morphology is the product of development, the process through which a single fertilized egg cell gives rise to an entire organism.

Given that the DNA of (most) all cells in an animal is identical, how do different cells acquire the unique morphologies and functional properties required in the diverse organs and tissues of the body?

We now understand that this process occurs through the selective expression of distinct subsets of the many thousands of genes in any animal’s genome in different cells. How genes are turned on and off in different cells over the course of animal development is an exquisitely orchestrated regulatory program. If morphological diversity is all about development, and development results from genetic regulatory programs, then is the origin of diversity directly related to genetic regulatory programs?

Yes.

But to understand how diversity emerges, and if evolution is an adequate explanation, it must first be understood how the genetic regulatory mechanisms operate in development. What is the genetic toolkit of development and how does it operate to build animals? The foremost challenge for embryology has been to identify the genes and proteins that control the development of animals from an egg into an adult.

Early embryologists discovered that localized regions of embryos and tissues possess properties that have long-range effects on the formation and patterning of the primary body axes and appendages. Based on these discoveries, they postulated the existence of substances responsible for these activities. A small fraction of all genes in any given animal constitute the toolkit that is devoted to the formation and patterning of the body plan and body parts.

Two classes of gene products with the most global effects on development are of special interest: families of proteins called transcription factors that turn the expression of many other genes during development either on or off, and sophisticated signalling networks direct transcription factors to do it at the right time, at the right place. The exquisite sophisticated orchestration how cells do this is truly awe-inspiring. Let's have a look:

Members of signalling pathways mediate short- and long-range interactions between cells. The expression of specific transcription factors and signalling proteins marks the location of many classically defined regions within the embryo. These proteins control the formation, identity, and patterning of most major features of animal design and diversity.

Thom,1989 writes: We consider the concept of predetermination of a geometrical shape/form of living species to be the most appropriate. The matrix on a cell surface will be changed after each cell event according to the rule(s) dictated by the morphogenetic field of an organism. There is a connection between the morphogenetic code on the cell surface, cell motion law(s), and the geometry of an embryo.  It is impossible to create a formalization of morphogenesis that is not based on a “deterministic concept”.

Does that not sound suspiciously like pre-programmed design?

Amongst several other essential mechanisms, one is the

Combinatorial gene regulation by modulation of relative pulse timing.

For example, the transcription factors Msn2 and Mig1 combinatorially regulate their target genes through modulation of their relative pulse timing.  

Regulation through relative signal timing is common in engineering and neurobiology, and incredibly, it is also employed by cells, and it functions also within the signalling and regulatory systems of them. In order to respond to environmental conditions, cells make extensive use of combinatorial gene regulation, in which two or more transcription factors co-regulate common target genes.

While most analysis of combinatorial regulation presumes that the concentrations of transcription factors in the nucleus are regulated in a continuous (non-pulsatile) manner, recent work has identified a large and growing list of transcription factors that activate in pulses.

My comment: According to Wiki, regulation is an abstract concept of management of complex systems according to a set of rules and trends. Amazingly, these types of rules exist in various fields of biology.

Question: Is setting rules and trends, and management not something only done by intelligence? Can a mindless process like evolution set rules of regulation? In order to do so, is there not before anything else, knowledge required about what has to be regulated, why, and how? Is not knowledge required to implement a functional regulation of whatever it might be, and so as well biological systems, in order for them to be able to adapt to the environment for successful survival and development?

For successful gene regulation, cells must know how to combine the right transcription factors, and how they find the right target genes ( interface compatibility of binding of the TF's to the right promoter sequence on the gene has to be pre-programmed and set up right from the beginning )

Pulsatile regulation has been observed in bacteria, yeast, and mammalian stress response and signalling pathways.  In these systems, inputs typically modulate the pulse frequency, amplitude, and/or duration of individual transcription factors to regulate genes.

What functions does pulse timing modulation provide for the cell? One of the most fundamental concepts in combinatorial regulation is that cooperative interactions between transcription factors can increase their probability of simultaneous binding to a promoter, to implement cis-regulatory logic.

In communications, modulating the phase of a periodic signal relative to a reference signal is widely used to encode information.

One author claims that : "Cells seem to have evolved a related strategy by encoding aspects of the extracellular environment in the relative timing with which different transcription factors pulse."

Is it?  My comment: Is evolution not rather an impotent mechanism to explain the origin of these ultrasophisticated coding and communication systems, precisely because one fundamental prerequisite, it lacks, namely intelligence?  


The author mentions that " Cells evolved a strategy". This is teleology. Pure and simple.  According to Wiki, Strategy (from Greek "art of troop leader; office of general, command, generalship") is a high-level plan to achieve one or more goals under conditions of uncertainty.

Pulsatile dynamics (both periodic and aperiodic) have been discovered in a growing list of central signalling and regulatory pathways. which are known to interact, or crosstalk, with one another.

The oscillation phase shift between Wnt and Notch signalling is critical for segmentation during development. Dynamic signalling, i.e., the relative timing between oscillatory signals, encodes essential information during multicellular development.

My comment:  Pulses activating transcription factors. Pulsatile regulation observed in bacteria, yeast, and mammalian signalling pathways.  Pulse inputs modulating the pulse frequency, amplitude, and/or duration of individual transcription factors to regulate genes. Combinatorial regulation where cooperative interactions between transcription factors implement cis-regulatory logic. Cells using the strategy of modulating the phase of a periodic signal relative to a reference signal which is widely used to encode information. Pulsatile dynamics (both periodic and aperiodic) being part of a growing list of central signalling and regulatory pathways,  interacting, or crosstalk, with one another.

If that were not enough, cells use an oscillation phase shift between Wnt and Notch signalling, which is critical for segmentation during development. Dynamic signalling, i.e., the relative timing between oscillatory signals, encodes essential information during multicellular development.

Extremely sophisticated Pulse oscillations and phase shift variations encoding information which direct transcription factors to express, that is, activate or repress genes by teamwork and in a combinatorial way, and crosstalk amongst them- just WoW !!

Design, or non-design? I leave it to you to decide. But one thing, i think we can be certain:  Mutations, natural selection, gene drift of flow - nope. Charly, 150 years ago, could have claimed that based on ignorance and blind faith. Today - sorry. But it is not justified -. time to put these old, false, and in so many ways refuted and disproven ideas to rest.


Ultrasophisticated communication systems have ALWAYS been observed to have intelligence as origin. What to say, when they are far far more complex than any made by human intelligence ?!!

" Creationists have no clue how evolution works " Is it? Who has ?

One of the often heard rebuttals of atheists which use evolution as crutches to back up their views that God is not required is:

" You don't know how evolution works".

This demonstrates that:

They do think they know how evolution works. and that they, in reality, have NO CLUE what they are talking about.

In the same sense, as on top of making complex factories, first  is the elaboration of a master plan, a general layout of an industrial complex of various interlinked factory buildings, and below are the blueprints to make the individual factories, compartments, assembly lines, machines, robots, machine elements, basic building blocks, material specification, etc.
in biology, there is as well a master plan, which outlines the entire structure and body architecture of an organism. That master plan is stored in the genome, in a section, called homeobox.

Homeobox genes are a large family of similar genes that direct the formation of many body structures during early embryonic development. A homeobox is a DNA sequence found within genes that are involved in the regulation of patterns of anatomical development morphogenesis in animals, fungi, and plants. In humans, the homeobox gene family contains an estimated 235 functional genes and 65 pseudogenes, which are structurally similar genes that do not provide instructions for making proteins. Homeobox genes are present on every human chromosome, and they often appear in clusters. Many classes and subfamilies of homeobox genes have been described, although these groupings are used inconsistently.

Homeoboxes have been found in fungi, plants and animals. In each "kingdom" homeobox genes occupy a key position in the genetic control of either cell differentiation, morphogenesis and or body plan specification.

The degree of sequence conservation of the homeodomain is extremely high indicating strong functional constraints leading to a high pressure to retain the homeobox sequences constant.

Single mutations in HOXA1 sequence, is crucial in the determination of severe cardiovascular malformations. Mice knock out for Hoxa1, show defects as interrupted aortic arch, aberrant subclavian artery and Tetralogy of Fallot. Hoxa1 play a key role in the arrangement of the great arteries and heart outflow tract.

Mice knockout for Hoxa3 gene, show cardiac abnormalities and links between circulatory and respiratory systems. The HOXC5, HOXA5 and HOXB5 expression, induce a development of new pharyngeal arches containing a new aortic arch artery with regular flow. HOXC9 is overexpressed, in human smooth muscle cells and the cardiovascular system during embryogenesis.

What does that demonstrate?  In a vast gene sequence space, functional Gene regulatory sequences, Master genes that direct body development, are under severe constraint, and only very specific homeobox sequences are functional, and even A SINGLE MUTATION has catastrophic consequences.

SORRY, Charly, but once again, your ideas are being refuted and falsified. Sad that you are not here to clean up the mess you left, and so many still believe in your unproven claims, nothing else than guesswork, which is driving so many away from the MASTER, that invented all this stuff.

So. What does science say to this ?? Lets see.

Evolution of Homeobox Gene Clusters in Animals: The Giga-Cluster and Primary vs. Secondary Clustering

https://www.frontiersin.org/articles/10.3389/fevo.2016.00036/full

There is uncertainty in our understanding of homeobox gene cluster evolution at present. This relates to our still rudimentary understanding of the dynamics of genome rearrangements and evolution over the evolutionary timescales being considered when we compare lineages from across the animal kingdom.

OH NO !!! I can't believe it !! They have no clue? Right. Pro scientists working on the field which try to find out how the instructions of gene expression and repression emerged, admit, they have no idea !!

Well, they are at least honest to admit the situation.

But the ultracrepidarian " i know it better " experts we deal with on FB feel themselves in the position to tell us the Levites, and educate us on evolutionary developmental biology. We, creationists, are the don't know ists and ignorantes, who do have no clue how evolution works... HÁ !!

Some reasons why life is an all or nothing process

Availability of some of the basic building blocks for life
Each of the following global energy Cycles are essential for advanced life on earth: the Water Cycle, Carbon Cycle, Nitrogen Cycle, Global Carbon Cycle, Phosphorus, Iron, and Trace Mineral cycles. They are also interdependent with each other. Which came first?

Nitrogen is essential for the make of nucleic acids and proteins—the two most important building blocks of life. The availability of nitrogen in the form of ammonia which microorganisms can uptake,  to produce DNA and amino acids, depends on the nitrogen cycle. But the nitrogen cycle depends on cooperating microorganisms, operating in a coordinated manner, which promotes a fine ecological cycle balance. These microorganisms could not emerge without DNA and nucleic acids.
What emerged first: DNA and nucleic acids to make these microorganisms, essential for the nitrogen cycle, or the Nitrogen cycle, essential for the production of these building blocks, making the origin of micro-organisms possible?
 
The carbon dioxide level in the atmosphere must be just right: If greater: runaway greenhouse effect would develop.  If less: plants would be unable to maintain efficient photosynthesis

Carbon has unique properties that make it the backbone of all organic compounds. Carbon must be made bioavailable through carbon dioxide fixation which depends on specialized enzymes that perform the task. In all living organisms, the central metabolic pathways promote the sugar-phosphate reactions which provide the precursor building blocks required for the make of RNA, DNA, lipids, energy, and redox coenzymes and amino acids—key molecules required for life. No non-enzymatic pathways to fix Carbon dioxide were likely responsible on early earth ( they would likely have disintegrated with UV radiation ). It takes enzymes to make the precursor building blocks of life. But it requires the precursor building blocks of life to make the key molecules, required to make enzymes which fix carbon. What came first?

Adaptation of life to the environment - essential for life
The ability to change over time in response to the environment is fundamental and is determined by the organism's genetics, its gene regulatory network, and modulation of the signaling pathways at transcriptional, post-transcriptional and post-translational levels. At least five life-essential signaling networks dependent on preprogrammed intracellular information transmission systems respond to environmental stress. How could the first living Cell have survived without the mechanism implemented from day one?

Reproduction is essential for the survival of all living things.
Reproduction is essential for the survival of all living things and depends on DNA replication, which involves more than thirty specialized proteins. Each essential for the task. It takes proteins to make DNA replication happen. But it takes the DNA transcription and translation to make proteins. What came first?

The gene regulatory network:
What emerged first: Gene repression, or activation? Life would not exist without both....

What emerged first, genetic, or epigenetic information? Genetic information could not be expressed at the right time in the right place without the epigenetic information, when and where to do so.

Proteins and Catch22
Which came first, proteins or protein synthesis? If proteins are needed to make proteins, how did the whole thing start?" The end result of protein synthesis is required before it can begin.

Protein machines are needed to read the DNA, but these protein machines are themselves made upon the instructional blueprint stored in DNA.

The transition from RNA to DNA depends on Ribonucleotide reductase proteins. The make of proteins depends on the instructions from the instructional blueprint, stored in DNA.
DNA is required to make Ribonucleotide reductase proteins. But these proteins are required to make DNA. What came first?

Lipid Membranes
The Lipid membrane would be useless without membrane proteins but how could membrane proteins have emerged in the absence of functional membranes?

A living cell requires a protective lipid membrane, and a huge number of various types of life-essential membrane proteins, like proton pumps, receptor proteins, anchor proteins, channel proteins, transmembrane proteins, carrier proteins etc.  Lipid membrane and Membrane protein synthesis occur inside living Cells, protected by the Cell membrane, and a homeostatic milieu. Membrane protein synthesis depends on the ordered organized import of the basic building blocks to make them.  What emerged first, Cell membranes and membrane proteins, or their synthesis, if its synthesis depends on both?

Metabolic pathways
The central metabolic pathways like glycolysis or the Citric Acid cycle are essential to make Adenine triphosphate ( ATP ),  the energy currency in the cell, and amino acids, the basic building blocks of proteins. These metabolic pathways use enzymes, which are made through ATP and amino acids. How did these pathways emerge?

Metabolism, or replicator, what came first?
Both metabolism and replication are complementary processes. RNA is claimed to be the information carrier prior to DNA on early earth, and a catalyst at the same time. How could it have been so, without energy supply depending on metabolism?

Error check and repair
There are elaborate surveillance mechanisms, DNA and RNA quality control, and repair systems. The DNA and protein error check and repair system would have needed to be there from the beginning. What came first, RNA or DNA replication, or quality control, error check and repair mechanisms?

What came first, the software, or the hardware in the Cell ?
DNA is an information storage system like a hard disk of a computer and stores algorithmic (instructional) information.  What emerged first, the DNA molecule which equals to the hardware, or the blueprint stored through DNA, which equals a software? There is no reason for information processing machinery to exist without the software and vice versa.

RNA nor DNA outside of a living cell has no function, no purpose. To exercise its task, DNA must be part of a large factory-like production line, with each compartment exercising its specific purpose alongside the others in a cooperative manner, where one compartment depends on the product of another. That raises an insurmountable hurdle for unguided processes in early earth. If biochemical processes inside living cells only result in purposeful outcomes, if interconnected and interdependent like in a factory assembly line, how did the individual specific parts emerge, if they have no function by their own ?

Nothing exists outside of the Mind! God is Mind. Matter is an illusion of Consciousness.

Werner Heisenberg
“The atoms or elementary particles themselves are not real; they form a world of potentialities or possibilities rather than one of things or facts.” 

I think that modern physics has definitely decided in favour of Plato. In fact, the smallest units of matter are not physical objects in the ordinary sense; they are forms, ideas which can be expressed unambiguously only in mathematical language.

Of course, we all know that our own reality depends on the structure of our consciousness; we can objectify no more than a small part of our world. But even when we try to probe into the subjective realm, we cannot ignore the central order…In the final analysis, the central order, or 'the one' as it used to be called and with which we commune in the language of religion, must win out.

Sir James Hopwood Jeans
Today there is a wide measure of agreement, which on the physical side of science approaches almost to unanimity, that the stream of knowledge is heading towards a non-mechanical reality; the universe begins to look more like a great thought than like a great machine. Mind no longer appears as an accidental intruder into the realm of matter; we are beginning to suspect that we ought rather to hail it as a creator and governor of the realm of matter... 

The tendency of modern physics is to resolve the whole material universe into waves, and nothing but waves. These waves are of two kinds: bottled-up waves, which we call matter, and unbottled waves, which we call radiation or light. If annihilation of matter occurs, the process is merely that of unbottling imprisoned wave-energy and setting it free to travel through space. These concepts reduce the whole universe to a world of light, potential or existent, so that the whole story of its creation can be told with perfect accuracy and completeness in the six words: ‘God said, Let there be light’.

Bernard d'Espagnat
"The doctrine that the world is made up of objects whose existence is independent of human consciousness turns out to be in conflict with quantum mechanics and with facts established by experiment."

Martin Rees
In the beginning, there were only probabilities. The universe could only come into existence if someone observed it.

Freeman Dyson, Infinite in All Directions (1988), p. 18
What philosophical conclusions should we draw from the abstract style of the superstring theory? We might conclude, as Sir James Jeans concluded long ago, that the Great Architect of the Universe now begins to appear as a Pure Mathematician, and that if we work hard enough at mathematics we shall be able to read his mind. Or we might conclude that our pursuit of abstractions is leading us far away from those parts of the creation which are most interesting from a human point of view. It is too early yet to come to conclusions.

Physicists, especially the physicists of small things and microcosmic states, see matter and energy vanishing, virtual particles popping in and out of apparently 'nothing' and the indeterminacy of any material state. Some are beginning to see that information, that exists but has zero mass and carries zero energy, and therefore not material at all, is primary over both matter and energy and may even give rise to them. 

What is energy? In physics, energy is the property that must be transferred to an object in order to perform work on, or to heat, the object

Wiki describes energy as " property" . Why is energy not simply the ' force ' of Gods word in action? they talk about an object. But matter is not an object. matter is energy.... 

W.L.Craig: The quantum vacuum is not what most people envision when they think of a vacuum-that is, absolutely nothing. On the contrary, it's a sea of fluctuating energy, an arena of violent activity that has a rich physical structure and can be described by physical laws.

Space Is Not Empty, It’s Actually Full of Energy: The Quantum Vacuum

Quantum physicists discovered that physical atoms are made up of vortices of energy that are constantly spinning and vibrating, each one radiating its own unique energy signature. This is also known as "the Vacuum" or "The Zero-Point Field."

“A century from now, it will be well known that: the vacuum of space which fills the universe is itself the real substratum of the universe; vacuum in a circulating state becomes matter; the electron is the fundamental particle of matter and is a vortex of vacuum with a vacuum-less void at the center and it is dynamically stable; the speed of light relative to vacuum is the maximum speed that nature has provided and is an inherent property of the vacuum; vacuum is a subtle fluid unknown in material media; vacuum is mass-less, continuous, non viscous, and incompressible and is responsible for all the properties of matter; and that vacuum has always existed and will exist forever….Then scientists, engineers and philosophers will bend their heads in shame knowing that modern science ignored the vacuum in our chase to discover reality for more than a century.”

At the turn of the nineteenth century, physicists started to explore the relationship between energy and the structure of matter. In doing so, the belief that a physical, Newtonian material universe that was at the very heart of scientific knowing was dropped, and the realization that matter is nothing but an illusion replaced it. Scientists began to recognize that everything in the Universe is made out of energy. 

What’s even more fascinating is that the “stuff” within this space can be accessed and used. This was experimentally confirmed when The Casimir Effect illustrated zero point or vacuum state energy, which predicts that two metal plates close together attract each other due to an imbalance in the quantum fluctuations.

Biological organisation demonstrates that low-level functions support top-level function

On the lowest level are compartments that produce the basic building blocks of life, RNA and DNA, carbohydrates, and fatty acids, which we can call subcomponents. These support the top-level function. This forms a complete interdependent unity, where the overarching function depends on the production of the basic building blocks on the lowest end, which is assembled into proteins, co-factors, holo-enzymes, assembly lines, organelles, and last not least, functional cells.


Picture from Undeniable, Douglas Axe, page  78

The hierarchical structure characterizes the relationships between parts. In this scheme, the parts at intermediate levels (between the elementary constituents and the functional whole) are referred to as components. The number of intermediate levels and components depends both on the complexity of the whole.  Fact is that the subparts or elements must perform their functions in the correct manner, in order for the whole thing its large function. There is an interdependence between the lowest level and the top level. If one of the lower elements is missing or does not work properly, global mal-function is the consequence or no function at all. For example:

- No glycine amino acids, no pyrimidines, no DNA - no life.
- No Watson Crick base pair fine-tuning, no DNA - no life.
- No topoisomerase II or helicase proteins, no DNA replication - no life perpetuation.
- No peripheral stalk, a subunit in ATP synthase nano turbines, no energy supply trough ATP for biological cells, no advanced life.
- No cleavage of tRNA during its biosynthesis, tRNA's will not be useful for the cell, no life. 
- No nitrogenase enzymes to fix nitrogen in an energy demanding, triple bond breaking process, no ammonia, required to make amino acids - no nitrogen cycle - no advanced life.

Life is organized in a hierarchical way of sub-elements and parts which contribute in an interlocked, interdependent manner to promote  a final function , and each part contributing in a coordinated way to the whole is essential and irreducible. 

Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system.
In other words: Why would natural selection select an intermediate biosynthesis product, which has by its own no use for the organism, unless that product keeps going through all necessary steps, up to the point to be ready to be assembled in a larger system?  
A minimal amount of instructional complex information is required for a gene to produce useful proteins. A minimal size of a protein is necessary for it to be functional.   Thus, before a region of DNA contains the requisite information to make useful proteins, natural selection would not select for a positive trait and play no role in guiding its evolution.

The setup of hierarchical levels of organization, where the function and proper set up of the higher level depends on the lower level, has always been observed to be due to intelligent planning, setup, and design. The same is true for the setup of wiring diagrams in an electrical engineering blueprint or a schematic of an integrated circuit. The genomic program of development demonstrates a multilayered, hierarchical,network-like architecture based on nodes and modules, orchestrating a specific pattern of gene expression. The fundamental role of upper-level Gene regulatory networks is to set up in embryonic space a progressive series of regulatory states, which functionally define first the regions of the body with respect to its axes; then the location of the progenitor fields of the body parts; then the subparts of each body part. Each dGRN module is controlled to be expressed at the right time, and as such, little if no variation is possible. It constitutes an interlocked system. GRNs are logic maps that constrain, orient and direct in detail each module in the lower hierarchy level so that a given gene is expressed at a given time and place. The tight functional constraints under which these systems of dGRNs operate result in catastrophic consequences if altered by mutation and selection mechanisms.

The setup of distant specific goals is always something done by intelligence ( teleology ). Modern biological sciences try to avoid teleology at all cost ( Not an easy task - and often not successfully )

Molecules, basic building blocks of life, proteins, cell compartments, organelles, and organs have often ONLY and EXCLUSIVELY function when employed as a part and ingredient in a complex organizational biological system. But that functional complexity is only achieved by building up lower levels of complexity, which contributes to that higher overarching order and purpose. Therefore, their origin cannot be explained by gradual Darwinian evolution, which depends on slow improvement and positive functionality and fitness on each evolutionary step over a long period of time.

A few reasons and motivations why people try to deny Gods existence first to themselves, and in order to enforce/strengthen their own convictions, try to find others that confirm what they want to be true, is
- fear of the unknown of what might come when they die
- personal experience which made them feel angry at God
- rebellion against Gods moral codes and laws restricting their sins and immoral behaviour which they know is wrong, but they love, and do not want to give up
God-deniers want to find reasons which permit them to keep on fearlessly doing what they want despite knowing it is not right, and if they succeed to deny God, there is no reason to fear him, nor any consequences.
The problem with that is, that they cannot entirely annihilate their conscience, and there is always a cognitive dissonance between what they want to be true, and what they know is true because reason and emotions conspire against the No-God-hypothesis.

The transcription factor code - another epigenetic language comes to light 

https://reasonandscience.catsboard.com/t2061p125-my-articles#6271

Genes are like a book, which contains the instructions, blueprints, and manuals to make the workhorses of the Cell, proteins, amongst many other things. Proteins have to be produced at the right time, and that depends on the availability of food sources, environmental conditions, and ontology ( development of the organism )

Membrane proteins on the surface of cell membranes transmit the information received from the outside to signalling networks and signal transduction cascades, which are connected to the nucleus, and to chromatin. Cellular signalling cascades regulate the activity of transcription factors that convert extracellular information into gene regulation. The information received is interpreted and directs gene expression.

The right cell response relies upon the expression of the correct genes amongst 20 thousand genes in humans, and the cell machinery has to find the right ones. How does it achieve this feat? 

As an analogy, let's suppose someone has to find a book in a library, amongst 20 thousand books. Of course, we use the alphabet or numbers, to tag each book with a short code, and inform the library classification software. In an easy click, the book can be found. But if a functional library classification system had to be invented, and no alphabetical or numerical code would exist? How could a gradual evolutionary development come up with such informational system?   One simpler alternative ( nonetheless far beyond what natural mechanisms could do ) would be to tag each book with an individual sign. So we would require 20 thousand different signs, one for each book. Not very practical, indeed.

The cell faces the same problem. The selective expression of any one of the 20 thousand human genes is accomplished primarily through the interaction of proteins called transcription factors. The binding of a set of such factors ( TFs) acts as a molecular switch for the activation of RNA polymerase and other components of the transcriptional machinery.

Gene expression is controlled by binding of a TF to a regulatory region in DNA, or promoter. TFs that bind to promoter DNA sequences are responsible for either positively or negatively influencing the transcription of specific genes, essentially determining whether a particular gene will be turned "on" or "off" in an organism. ( Equivalent of either picking a book in the shelf of the library, or remain it there )  Much of the complexity in differentiation in animal and plant cells can be attributed to elaborate systems made up of short (6 to 8 base pair) cis-regulatory DNA sequences or motifs, as well as the TFs that bind to the motifs, interact with each other to form complexes and recruit RNA polymerase II. ( That would be equivalent of an autonomous library book retrieval systems, able to recognize the tag on each book, read it, and take the right book out of the shelf ).   TFs generally bind to these specific DNA sequences. Their affinity for these target sequences is roughly one million times higher than their affinity for any other DNA sequence.

In order for an automated library book retrieval and classification system to work, there must be 

1. All books in the library tagged 
2. All books stored at the right place in the library section and shelf 
3. An operational library classification system and software, and the information where to find each book 
4. Automated, programmed robots with recognition software, able to direct themselves to the right place and retrieve the book, and make it ready to be read. 

inside Cells, the same organization has to be fully setup

1. All genes with promoter regions and stop signs
2. All genes organized in the right order
3. An operational gene regulatory network, able to respond to external stimuli, food resources, and development 
4. Signal transduction cascades, Chromatin, Transcription factors with binding sites that are able to recognize promoter regions in the genome, and bind to them, and activate the transcription machinery. 

If one of these parts is missing, nothing goes. 

If each TF protein would have to be coded for by the expression of another gene, which would, in turn, require another protein transcription factor and so on, that would lead to an infinite regress.
However, if a set of proteins is involved, then different combinations can be used for different genes. Thus a smaller number of regulatory proteins can control a large number of genes.

The transcription factor Code
Usually, a combination of several (as many as six) transcription factors is necessary to form a transcription complex which can harness and activate the RNA polymerase to initiate transcription at the right starting point. If a set of proteins is involved, then different combinations can be used for different genes. Thus a smaller number of regulatory proteins can control a large number of genes.

In addition, this provides the means for multiple control at the level of the gene, which has the advantage that transcription may be regulated in a quantitative rather than in an all-or-none manner, and also for producing a network of interacting genes, since the protein product of one gene can affect the expression of another. So one has a combinatorial principle at work here operating at the level of a combination of proteins. In the case of zinc finger proteins, the principle also operates within individual proteins, where different subdomains can be combined to give greater variety or precision of recognition-a microcosm, as it were, of the macroscopic picture. 

Multiple TFs can accumulate, creating a bulk the size of a ribosome. Once bound together, changes to the functional domains of a TF and/or covalent interactions with other factors can turn transcription on or off, depending on whether they allow or prohibit the recruitment of RNA polymerase. Two TFs bound at sites near one another on the DNA strand can combine to form a dimer and bend the DNA in what is believed to be part of the activation process.  Some TFs are believed to act as tethering elements between distant enhancers and promoters by forming connections with other proteins.

Combinatorial interactions among transcription factors (TFs) are critical for integrating diverse intrinsic and extrinsic signals, fine-tuning regulatory output and increasing the robustness and plasticity of regulatory systems. In higher eukaryotes, transcription factors (TFs) rarely operate by themselves, but rather directly or indirectly interact with specific partner TFs or chromatin regulators when binding to enhancers. It has been estimated that roughly 75% of all metazoan TFs heterodimerize with other factors 

A group of Broad scientists has found that TFs' binding sites within enhancers cluster in distinct patterns reflecting the factors' roles in gene expression control. These patterns may constitute a position-based code. The TF clusters may constitute a general regulatory code, with different cell types substituting specific TFs to activate different sets of enhancers. 

There is more. 

Post-translational modification code for transcription factors
Post-translational modification PTMs can involve covalently linking chemical groups, lipids, carbohydrates or (poly)peptide chains to amino acids of the target protein during or after its translation. Cellular responses to environmental or physiological cues rely on transduction pathways that must ensure discrimination between different signals. These cascades ‘crosstalk’ and lead to a combinatorial regulation. This often results in different combinations of posttranslational modifications (PTMs) on target proteins, which might act as a molecular barcode. A PTM code is necessary in the context of transcription factors regulating multiple processes. Thus, the coding potential of PTM combinations should both provide a further layer of information integration from several transduction pathways and warrant highly specific cellular outputs.


This is pretty amazing. Evolution, or design? You decide.  

More:
Transcription factors (TF)
https://reasonandscience.catsboard.com/t2738-transcription-factors-tf

Homeobox and Hox Genes

This is pretty creepy: the gene order on the chromosome of unrelated species is identical to the Anterior -> Posterior order of their gene expression in the developing embryo. How to explain this - if not by design?

To understand the major trends in animal diversity and if the various kinds of morphology are due to evolution, we must first understand how animal form is generated.

It is interesting, that despite of several decades of intensive studies and scientific investigation, one of the key issues remains unsolved.

Homeobox and Hox Genes

Sections of genes codify Transcription factors, which are used by the cell to turn other genes on or off. There is a class of proteins, containing a region of about sixty amino acids called “homeobox.” This class of proteins is called Hox proteins. In subsequent years homeotic proteins and other classes of control proteins have proven to be master regulators of developmental programs in animals. In animals, a master switch sets in train a whole cascade of lesser switches, where the initial regulatory protein turns on the genes for other regulatory proteins, which turn on other regulatory proteins, and so on. Eventually, after a pyramid of control switches, a regulatory protein activates a gene that actually does some of the construction work to build an animal’s body. But there’s another complication. A gene in an animal cell might be regulated not by just one or a few proteins, but by more than ten. What’s more, there may be dozens of sites near the gene at which the regulatory proteins might bind, with multiple separate sites for some regulatory proteins. 1

Animal bodies contain many different kinds of cells that have to be positioned in definite relationships to other cells, in order to be formed into organs and to connect to other parts of the body.

Cal Tech biologist Eric Davidson emphasizes what the task of building an animal demands:
The most cursory consideration of the developmental process produces the realization that the program must have remarkable capacities, for development imposes extreme regulatory demands…Metaphors often have undesirable lives of their own, but a useful one here is to consider the regulatory demands of building a large and complex edifice, the way this is done by modern construction firms. All of the structural characters of the edifice, from its overall form to minute aspects that determine its local functionalities such as placement of wiring and windows, must be specified in the architect’s blueprints. The blueprints determine the activities of the construction crews from beginning to end.

Homeobox Genes and the Vertebrate Body Plan
This family of related genes determines the shape of the body. It subdivides the embryo along the head-to-tail axis into fields of cells that eventually become limbs and other structures.  Starting as a fertilized egg with a homogeneous appearance, an embryo made of skin, muscles, nerves and other tissues gradually arises through the division of cells. Long before most cells in the emerging body begin to specialize, however, a plan that designates major regions of the body-the head, the trunk, the tail and so on is established. This plan helps seemingly identical combinations of tissues arrange themselves into distinctly different anatomical structures, such as arms and legs. Individual genes mediate some of the developmental decisions involved in establishing the embryonic body plan.

The make of plans and blueprints prior something is made, and making decisions, is ALWAYS the result of intelligence.

Key is a family of genes, known as homeobox genes, that subdivides the early embryo into fields of cells with the potential to become specific tissues and organs.

Hox genes encode a group of transcription factors, responsible for developmental processes and the establishment of the body plan. All Hox genes and many other developmental transcription factors contain the homeobox, a DNA sequence encoding the functional DNA-binding domain. Hox genes are known for their colinearity: conserved arrangement on chromosomes that is the same as their order of activation along the body axis. The regulation is very precise, for example, the regions of activity of Hox genes are tightly confined to specific rhombomeres ( see picture below ) or to segments of the vertebrate anteroposterior body axis

The vertebrate Hox genes are synchronized: the expression domains of paralogs ( either of a pair of genes that derive from the same ancestral gene )  from the A, B, C and D clusters are virtually identical

The mechanisms responsible for the synchronous regulation of Hox genes and the molecular function of their colinearity remain unknown. Despite 35 years of active research, the mechanisms of Hox gene regulation have remained elusive. It has been argued that chromatin structure and histone demethylation play important roles in activation of Hox genes, but the mechanism precisely directing chromatin modifications to specific loci at the right time remains mysterious. Ultraconserved regions and regulatory elements have been found within the coding sequences of Hox genes, but the key questions remain unanswered. It is unknown what mechanism could be responsible for the exceptional synchronous colinearity of Hox gene clusters and the conserved synteny of other pairs of groups of homeobox-containing genes, however, the topology of chromatin has been proposed to play a role in the regulation of these genes. 2

1. Behe, Edge of evolution, page 116
2. https://www.nature.com/articles/srep35415#ref32