Biochemical controls: the kidney (Introduction)
by David Turell 
, Monday, April 25, 2022, 20:47 (527 days ago)
The kidney does manythings at once to produce proper urine:
https://medicalxpress.com/news/2022-04-key-urinary-kidney.html
"Proper function of the kidney is critical for concentrating urine, regulating blood pressure, and for the tight control of electrolyte levels in the blood. The kidney achieves these important functions through many microscopic functional units, called nephrons. These nephrons consist of different segments with distinct functions. How these segments form during development and how their function is maintained in the adult is only partially understood.
***
"The distal nephron is particularly important for the ability of the kidney to concentrate urine, regulate blood pressure, and control calcium and magnesium blood levels. Parts of the distal nephron have specific salt transporters, which are the main targets of medicine's most effective diuretics, used in the treatment of hypertension and chronic kidney disease. Thus, understanding how their function is regulated has important implications for these common diseases.
***
"Previously, Marneros showed in work published in Developmental Cell in 2020 that AP-2β is required for the formation of the segment of the distal nephron that is targeted by thiazide diuretics: the distal convoluted tubule. This prompted him to ask whether the closely related protein AP-2α also has a function in the kidney. His team found that while AP-2β function in the kidney is required for survival by regulating the development and function of distal convoluted tubules, AP-2α is important for the proper function of a different segment of the distal nephron, called the collecting duct, which is involved in the kidney's ability to concentrate urine. Notably, loss of even only half of AP-2β levels causes progressive kidney disease, whereas complete loss of AP-2α resulted in less severe kidney abnormalities.
"'These findings show that AP-2α and AP-2β are important regulators of distinct segments of the distal nephron. These new observations in genetic mouse models are important contributions to our understanding of how specific segments of the kidney are regulated on a molecular level," says Marneros."
Comment: As in all these situations, everything must work together from the start, or it won't work. That is irreducible complexity as must be fully designed from the start to work properly. Mutating it bit by bit is impossible. This intact functkon had to first appear in the Cambrian explosion.
Biochemical controls: how enzymes work
by David Turell , Monday, April 25, 2022, 21:08 (527 days ago) @ David Turell
Picking their activity apart:
https://www.sciencedaily.com/releases/2022/04/220425104932.htm
"This concept is known as "electrostatic stress." For example, if the substrate (the substance upon which the enzyme acts) carries a negative charge, the enzyme could use a negative charge to "stress" the substrate and thus facilitate the reaction. However, a new study by the University of Göttingen and the Max Planck Institute for Multidisciplinary Sciences in Göttingen has now shown that, contrary to expectations, two equal charges do not necessarily lead to repulsion, but can cause attraction in enzymes. The results were published in the journal Nature Catalysis.
"The team investigated a well-known enzyme that has been studied extensively and is a textbook example of enzyme catalysis. Without the enzyme, the reaction is extremely slow: in fact, it would take 78 million years for half of the substrate to react. The enzyme accelerates this reaction by 1017 times, simply by positioning negative and positive charges in the active centre. Since the substrate contains a negatively charged group that is split off as carbon dioxide, it was assumed for decades that the negative charges of the enzyme serve to stress the substrate, which is also negatively charged, and accelerate the reaction. However, this hypothetical mechanism remained unproven because the structure of the reaction was too fast to be observed. (my bold)
***
"Unexpectedly, the negative charges of enzyme and substrate did not repel each other. Instead, they shared a proton, which acted like a kind of molecular glue in an attractive interaction. "The question of whether two equal charges are friends or foes in the context of enzyme catalysis has long been controversial in our field, and our study shows that the basic principles of how enzymes work are still a long way from being understood," says Tittmann. The crystallographic structures were analysed by quantum chemist Professor Ricardo Mata and his team from Göttingen University's Institute of Physical Chemistry. "The additional proton, which has a positive charge, between the two negative charges is not only used to attract the molecule involved in the reaction, but it triggers a cascade of proton transfer reactions that further accelerate the reaction," Mata explains.
"'We believe that these newly described principles of enzyme catalysis will help in the development of new chemical catalysts," says Tittmann. "Since the enzyme we studied releases carbon dioxide, the most important greenhouse gas produced by human activities, our results could help develop new chemical strategies for carbon dioxide fixation.'"
Comment: this shows how enzymes work, as if they knock two heads together, and demand cooperation. Enzymes force reactions to occur at the high-speed life's biology requires. Each giant enzyme molecule is precisely designed for each reaction it speeds up. Organic chemistry uses molecules that won't react quickly by themselves. Unfortunate, but those molecules are the only ones that will work. God knows what He is doing even if dhw has doubts with his second-guessing. It seems agnostics know better than God how to do things.
Biochemical controls: the kidney pumps blood
by David Turell , Wednesday, May 18, 2022, 15:24 (504 days ago) @ David Turell
The kidney doesn't just filter blood, it pumps it along:
https://medicalxpress.com/news/2022-05-reveals-kidney-cells-dont-filter.html
"Human kidneys are an intricate network of tubes that process roughly 190 quarts of blood every day. Lining these tubes are epithelial cells that transport blood through the kidneys and circulate it back into the body. How these immobile cells generate the mechanical force needed to do their job is not fully understood. To unlock the secrets of this fluid transport process, a Johns Hopkins mechanical engineer has created a device that measures mechanical forces generated by both healthy and diseased kidney cells.
"'Fundamental physical laws say that you need forces to move things. In this case, the cells are not moving, but they are moving fluid. The question then becomes how do they do this?" said Sean Sun, a professor in the Whiting School of Engineering's Department of Mechanical Engineering and a core member of the Institute for NanoBioTechnology.
***
"The researchers noticed that kidney epithelial cells behave like mechanical fluid pumps and actively generate a fluid pressure gradient. The fluid pumping behavior is characterized by a pump performance curve, which is very much like a water pump in a house. Most people believe that kidneys behave like a conventional filter, which needs external pressure to move fluid. However, Sun and his team showed that cells can actually generate the needed pressure themselves—an insight with important implications for understanding kidney physiological function.
"'Everyone hears that kidneys filter blood, but conceptually that is incorrect. What we showed is that kidney cells are pumps, not filters, and they are generating forces," Sun said."
Comment: kidney blood vessels are extremely tiny, and the arterial blood delivered to them under pressure must be reduced to almost zero for proper filtration. That an extra push is designed into kidney cells is not surprising, but is necessary. Such complexity is irreducibly complex as it must be designed all at once for the kidney system to work.
Biochemical controls: controlling cell protein output
by David Turell , Tuesday, May 31, 2022, 19:20 (491 days ago) @ David Turell
The body has control systems that drive production and slow production in a tight fashion:
https://phys.org/news/2022-05-decoding-protein-cells-healthy.html
"Cells produce proteins like little factories. But if they make too much at the wrong times it can lead to diseases like cancer, so they control production with a process called RNA interference (RNAi).
***
"They [a research group] recently discovered how RNAi's workhorse protein Argonaute (Ago) leverages limited resources to keep protein production on track.
"It's important to understand exactly how RNAi works because it's such a basic and heavily used process, Joshua-Tor said. It also offers a kind of safety net for therapeutics because it doesn't make permanent changes to cells and can be reversed.
***
"Ago helps cut off protein production by finding, binding, and destroying molecules called mRNA—which tell cells to make proteins. But the amount of Ago in the body pales in comparison to the amount of mRNA it must target. After destroying one MRNA molecule, the protein is still capable of finding another but it can't move on without help. Bibel discovered how cells use a process called phosphorylation to break Ago's grip on a mRNA target, allowing it to commute to the next.
"Bibel explains that their "theory is that having phosphorylation promote release is a way that you could free up Argonaute because when the target gets released, the guide's still there and it's super duper stable. So our thinking is that by phosphorylating it, you're going to free it to go repress other targets—because it's still totally capable of doing that work.'"
Comment: more evidence of purposeful design. Controlling production rates is vital, so start and stop controls must be designed together all at once.
Biochemical controls: intracellular electrical controls
by David Turell , Saturday, September 10, 2022, 15:54 (389 days ago) @ David Turell
Using very advanced techniques:
https://evolutionnews.org/2022/09/the-electric-cell-more-synergy-with-physics-found-in-...
"New findings reported in PNAS by Toyama et al. are uncovering a role for electrostatics in enzymatic activity. Simultaneously, the discovery may offer insight into the function of so-called “disordered proteins” that never fold into stable structures, and other proteins containing disordered regions that would seem to flail about like loose cables. But there is order in the disorder! How big is this discovery?
"Electrostatic interactions play important roles in regulating a plethora of different biochemical processes and in providing stability to biomolecules and their complexes (my bold)
"What the team from the University of Toronto found, discussed below, was only made possible by “solution NMR spectroscopy.” This technique allows them, for the first time, to measure the near-surface electrostatic potentials of individual atoms in proteins and follow changes in those potentials during an enzyme’s action.
"Our results collectively show that a subtle balance between electrostatic repulsion and interchain attractive interactions regulates CAPRIN1 phase separation and provides insight into how nucleotides, such as ATP, can induce formation of and subsequently dissolve protein condensates.
"CAPRIN1 (cell cycle associated protein 1) is an RNA-binding protein “localized to membraneless organelles playing an important role in messenger RNA (mRNA) storage and translation.” It may act as a negative regulator of translation, confining mRNAs in condensates at times to prevent overproduction of proteins. “CAPRIN1 is found in membraneless organelles, such as stress granules, P bodies, and messenger RNA (mRNA) transport granules, where, in concert with a variety of other RNA-binding proteins, it plays an important role in regulating RNA processing,” the paper explains.
"CAPRIN1 contains IDP tails at both ends which, it turns out, are the key to condensate formation. The Toronto team found, importantly, that ATP plays a dynamic role in the electrostatic changes of CAPRIN1, especially in its IDP regions. In brief, here is what happens (see Figure 5 in the paper). Specific amino acid residues in the IDP regions confer on them a net positive charge. This makes the tails repel each other, resisting condensate formation (and preventing self-association of the tails). When ATP attaches to the IDP regions, however, the net charge is reduced, permitting intermolecular interactions. As more ATP is added, the collection becomes neutral, and a condensate forms. Additional ATP inverts the electrical potential, making it negative. Electrostatic repulsion ensues again, causing breakup of the condensate, separating the contents and freeing them up for the next round.
"This implies that condensate formation has an electrical aspect to it. Since it relies on the sequence and position of specific amino acid residues, one might even call it an electric code.
***
"The information in the sequence of amino acids, and of the codons in the genes that encode them, appears to play critical roles in condensate formation and, simultaneously, in enzymatic behavior. Some amino acids they dub “stickers” promote phase separation. The specific electrostatic attractions and repulsions that give rise to the enzyme’s function during condensate formation and dissolution is dependent on the positions of these stickers.
"This remarkable revelation begins to give insight into the participation of cell coding with electrophysics. Get a charge out of that!
"CAPRIN1 coexists with negatively charged RNA molecules in cells and, along with FMRP and other proteins, is implicated in the regulation of RNA processing and translational activity. Thus, electrostatics play a central role in modulating the biological functions of this protein, and measurement of electrostatic potentials at each site along its backbone, as reported here, provides an opportunity to understand in more detail the important role of charge in this system. (my bold)
"The paper only investigated one enzyme, so caution is advised before generalizing. The authors feel, though, that this electrical code model will help explain many other processes that require molecules to come together, perform their work, and then separate. It’s the new Electric Cell."
Comment: electrostatic controls add another amazing layer to the complexity of the cell. Since all proteins contain charged areas the use of electrostatic charges to control molecular movements makes perfect sense.
Biochemical controls: reading DNA
by David Turell , Saturday, September 10, 2022, 16:16 (389 days ago) @ David Turell
At enormous speeds:
https://evolutionnews.org/2022/09/the-electric-cell-more-synergy-with-physics-found-in-...
"This team worked on a helicase enzyme named PcrA, which unwinds DNA for transcription. This enzyme works so fast (1000 bases per second!) it’s been like trying to describe the blur of a racecar speeding down a track. Using a new technique called “single-molecule picometer-resolution nanopore tweezers” (SPRNT), they were able to slow down the action and watch the racecar move with its “inchworm mechanism” one base at a time. This blends chemistry with another branch of physics, mechanics: “mechanochemistry.” (my bold)
"We recorded more than two million enzyme steps under various assisting and opposing forces in diverse adenosine tri- and diphosphate conditions to comprehensively explore the mechanochemistry of PcrA motion.…Our data reveal that the underlying DNA sequence passing through the helicase strongly influences the kinetics during translocation and unwinding. Surprisingly, unwinding kinetics are not solely dominated by the base pairs being unwound. Instead, the sequence of the single-stranded DNA on which the PcrA walks determines much of the kinetics of unwinding.
"The authors are not clear why this is. What is evolution up to? They figure that there must be a reason.
"Unlike protein filaments (e.g., actin), DNA is not a homogeneous track; sequence-dependent behavior may be the norm rather than the exception. Strong sequence-dependent enzyme kinetics such as those observed in our data likely affect PcrA’s role in vivo and could thereby exert selective pressure on both DNA and protein evolution. Therefore, sequence-dependent behavior should be carefully considered in future studies of any enzyme that walks along DNA or RNA, since the sequence-dependent kinetics may reveal essential features of an enzyme’s function. Such effects are almost certainly used by life to achieve various ends, and SPRNT is well suited to discovering how and why such sequence dependence occurs and opens the possibility of uncovering enzyme functions that were hereto unknown.
"Why are they giving the credit to blind evolution? If life uses “sequence-dependent kinetics…to achieve various ends,” that sounds like intelligent design, not evolution. Design advocates are accustomed to forgiving logical malapropisms like this. They look past the magical thinking and see the operation of a designing mind with foresight and purpose, intimately familiar with the laws of physics, able to write code to utilize those laws in precision operations. Now, it becomes clear that the precision goes deeper than previously known."
Comment: The final paragraph is pure ID thought. The unwinding speed of PcrA is amazing. What should be mentioned is all enzymes are giant molecules of thousands of amino acids. How did natural evolution find it?
Biochemical controls: an enzyme controls growth
by David Turell , Monday, October 31, 2022, 17:10 (338 days ago) @ David Turell
Its form is discovered:
https://phys.org/news/2022-10-three-dimensional-papp-a.html
"Danish researchers have determined the three-dimensional structure of the proteolytic enzyme PAPP-A. The results may allow us to better understand the basic biology that regulates linear growth of vertebrates. The same regulatory mechanisms are also involved in several age-related diseases, and thus, the research is an important step towards the development of novel types of drugs.
"The growth factor IGF plays a key role in human growth. In the absence of IGF signaling, we become dwarfs. Later in life, IGF is involved in age-related diseases, such as cancer and cardiovascular disease. In both cases, IGF must be converted from an inactive to an active form. This is what PAPP-A is able to do.
"'Seven years ago we discovered that the protein STC2 blocks the activity of PAPP-A, thus indirectly inhibiting the activity of the IGF growth factor. To block the activity, STC2 must form a complex with PAPP-A. We have studied this complex, and we now know its three-dimensional structure," Professor Claus Oxvig explains.
"'It is fascinating to see what a molecule, we know biochemically very well, actually looks like. PAPP-A is heart-shaped with an inner 'chamber'. But from a research point of view, the shape is not the most interesting feature. Rather, it is the interactions between the different elements of the molecule."
"There are still many unanswered questions about the molecular mechanisms, which regulate how much IGF is converted into the active form. It is likely that complex formation between PAPP-A and STC2 is highly regulated. Such a hypothesis is supported by earlier findings showing that natural human variants of STC2, in which just a single amino acid is substituted, form the complex with PAPP-A slightly slower. The consequence of this is that slightly more IGF can be activated by PAPP-A, resulting in an increase in height of up to 2.1 cm."
Comment: Same old point: this must be a designed mechanism because of the complexity of the enzyme molecule and the feed-back controls.
Biochemical controls: dumping cell waste
by David Turell , Monday, October 31, 2022, 18:25 (338 days ago) @ David Turell
A new control found:
https://phys.org/news/2022-10-cellular-mechanism.html
"A vast number of biological reactions occur inside cells, generating various byproducts. Some of these can be highly reactive molecules, and if they build up inside cells they can cause stress and damage. One class of these molecules, reactive sulfur species (RSS), are known to play biological functions, but it was unknown how cells respond to an accumulation of RSS. Now, researchers have described a system by which excess RSS can be actively transported out of cells.
"Chemical reactions constantly occur in cells, including two opposing reactions known as oxidation and reduction, and so it is key that this balance, known as "redox homeostasis," is maintained for the health of cells. RSS have been shown to act as antioxidants to protect against oxidative stress and maintain redox homeostasis, but an excess of RSS can also lead to sulfur stress.
"By creating a strain of mice that generated excessive RSS, the team were able to show that the levels of RSS rose in the extracellular space but not inside the cells, suggesting an active mechanism to transport RSS out of cells. "The strict regulation of the cellular levels of RSS that we observed suggests the presence of an adaptive cellular mechanism controlling the RSS levels, which most likely exists to protect against sulfur stress," explains senior author Professor Yoshito Kumagai.
"Transporter proteins are responsible for moving molecules out of cells. The team found that an amino acid called cystine was key in the export of RSS, suggesting that a particular transporter called SLC7A11 is involved in the transport of RSS. SLC7A11 is known to bring cystine into the cell while pumping another amino acid called glutamate out. As cystine is a sulfur-containing molecule, it was a surprising finding that SLC7A11 both imports cystine and exports RSS.
"Sulfur stress caused by high levels of RSS can lead to cell death. This is thought to be involved in a variety of human health conditions, including diseases of the heart (cardiomyopathy) and muscles (muscular dystrophy). Therefore, the surprising and significant results of this study will open new and previously unconsidered avenues for research into sulfur stress and related diseases."
Comment: this new system fits the definition of irreducibly complex. It had to be designed all at once.
Biochemical controls: protein folding follows rules
by David Turell , Monday, October 31, 2022, 22:06 (338 days ago) @ David Turell
As shown by an AI program:
https://www.scientificamerican.com/article/one-of-the-biggest-problems-in-biology-has-f...
"There’s an age-old adage in biology: structure determines function. In order to understand the function of the myriad proteins that perform vital jobs in a healthy body—or malfunction in a diseased one—scientists have to first determine these proteins’ molecular structure. But this is no easy feat: protein molecules consist of long, twisty chains of up to thousands of amino acids, chemical compounds that can interact with one another in many ways to take on an enormous number of possible three-dimensional shapes. Figuring out a single protein’s structure, or solving the “protein-folding problem, can take years of finicky experiments.
"But earlier this year an artificial intelligence program called AlphaFold developed by the Google-owned company DeepMind, predicted the 3-D structures of almost every known protein—about 200 million in all.
***
"There are 32 different component algorithms, and each of them is needed. It’s a pretty complicated architecture, and it needed a lot of innovation. That’s why it took so long. It was really important to have all these different inputs from different backgrounds and disciplines. And I think something we do uniquely well at DeepMind is mix that together—not just machine learning and engineering.
***
"One of the things we built in was this understanding of chemical bond angles and also evolutionary history using a process called multisequence alignment. These bring in some constraints, which help to narrow the search space of possible protein structures. The search space is too huge to do by brute force. But obviously, real-world physics solves this somehow because proteins fold up in nanoseconds or milliseconds. Effectively, we’re trying to reverse engineer that process by learning from the output examples. I think AlphaFold has captured something quite deep about the physics and the chemistry of molecules."
Comment: the underlying principle is every atom has a charge which dictates its contribution
to the folding by the attraction of the different charges. The AI program understand this. So, in thinking about design folding is not much of a design problem. It is the sequence of atoms in the protein that is required to be designed with an anticipated understanding of the desired protein function to be expressed. Not by chance.
Biochemical controls: enzyme controls repair
by David Turell , Friday, December 02, 2022, 00:20 (307 days ago) @ David Turell
A huge enzyme molecule has newly found function:
https://phys.org/news/2022-12-well-known-enzyme-quality-membrane-proteins.html
"An interdisciplinary team of scientists from Cologne, Heidelberg and Munich have discovered a new function of a well-known enzyme. The signal peptidase complex in the endoplasmic reticulum cleaves faulty membrane proteins to initiate their degradation.
"In our cells, the endoplasmic reticulum is responsible for producing and controlling proteins that get secreted from the cell. The signal peptidase complex cuts these polypeptide chains to remove signal peptides that allow proteins to reach the endoplasmic reticulum in the first place, so that the mature proteins can fulfill their specific functions.
"A research team led by Matthias Feige,...has now discovered that the signal peptidase complex has a hitherto unknown function in another key process in cell biology: the quality control of membrane proteins.
***
"Each cell is surrounded by a lipid bilayer, which protects the interior of the cell, but also demands for regulated transport of molecules and signals across this insulating layer to enable a plethora of cellular functions. Membrane proteins are integrated into this lipid bilayer and perform these functions. They are essential for cell survival and serve as the most important drug targets.
"To function properly, membrane proteins need to adopt a well-defined three-dimensional structure at the atomic level. Failures in this process can result in faulty proteins, which in turn gives rise to numerous diseases, including cancer as well as metabolic and neurodegenerative disorders.
"The team explored several disease-associated membrane proteins of our nervous system in order to better understand how our cells avoid that those faulty proteins damage them an and cause disease. During the course of their research, they observed that a protease—an enzyme that cleaves other proteins—initiates the degradation of the faulty mutant proteins. This degradation is essential to maintaining cellular function. However, they were unable to identify the protease involved. "All known candidates and commonly used inhibitors did not help us in our quest for the underlying molecular mechanism," said Feige.
"The breakthrough came after the researchers identified potential cleavage sites for the signal peptidase complex. "According to established textbooks, the signal peptidase complex cleaves off signal peptides during the maturation of secretory proteins and so far, this was mostly believed to be its sole function," Lemberg added. However, the researchers identified the signal peptidase complex as the protease they were searching for, revealing that it plays an essential role in membrane protein quality control.
"Subsequently, the interdisciplinary team of researchers identified several additional proteins that get cleaved and how this unexpected function might be regulated by the signal peptidase subunit SPCS1. "Since this factor is not essential for the initially described role in protein maturation, we realized that we were dealing with a previously unrecognized function," Feige explained.
"'Interestingly, SPCS1 is one of the only three genes that are down-regulated in all brain regions of Alzheimer's disease patients, suggesting that our findings may have important implications for our understanding of human biology and age-associated disorders," Lemberg added.
"In Alzheimer's disease, faulty proteins accumulate, which is thought to impair neuronal function. Feige concluded, "Our findings will help us to better understand how cells control the molecular shape of their proteins and lays the foundation for many future studies to come.'"
Comment: When cells first appeared, they had to have these housekeeping functions or would not have survived; another irreducibly complex requirement requiring contemporaneous design.
Biochemical controls: evolution of protein folding
by David Turell , Tuesday, March 07, 2023, 19:27 (211 days ago) @ David Turell
A new investigation:
https://phys.org/news/2023-03-creative-destruction-probing-evolution-proteins.html
"Proteins have been around a lot longer than we have—as building blocks of biological evolution, our existence depends on them. And now, researchers at the Georgia Institute of Technology are applying a 20th-century theoretical concept to study how proteins evolve, and it might lead to the answer of one of humanity's oldest questions: How did we become us?
"Inside a typical human cell are tens of thousands of proteins. We need so many because proteins are the skilled laborers of the cell with each one performing a specific job. Some lend firmness to muscle cells or neurons. Others bind to specific, targeted molecules, ferrying them to new locations. And there are others that activate the process of cell division and growth.
"A protein's specific function depends on its shape, and to achieve its functional shape—it's native state—a protein folds. A protein begins its life as a long chain of amino acids, called a polypeptide. The sequence of amino acids determines how the protein chain will fold and form a complex, 3D structure that allow the protein to perform an intended task.
***
"'"They discovered that once a protein can fold and achieve its 3D structure, when it is combined with another protein which has folded into a different 3D structure, that combination can easily become a new structure. "So maybe it's not as difficult as we thought to go from one structure to another," said Williams, professor in the School of Chemistry and Biochemistry. "And maybe this can explain the diversity of protein structures that we see today."
***
"Ever since the simplest and most ancient protein folds emerged on Earth billions of years ago, the number of folds has expanded to form the universe of protein function we see in modern biology.
"But the origins of protein folds and the evolutionary mechanisms at play pose central questions in biology that Williams and his team considered. For instance, how did protein folds arise, and what led to the diverse set of protein folds in contemporary biological systems, and why did nearly four billion years of fold evolution produce fewer than 2,000 distinct folds?
***
"In creative destruction, they explain, one open reading frame—the span of DNA sequence that encodes a protein —merges with another to produce a fused polypeptide. The merger forces these two ancestors into a new structure. The resulting polypeptide can achieve a form that was inaccessible to either of the independent ancestors, before the merger. But these new folds are not totally independent of the old. That is, a daughter fold inherits some things from the ancestral fold."
Comment: Some folding is automatic based on ion charges, but the overall controls are still a mystery. Design is required.
Biochemical controls: cell division DNA replication
by David Turell , Wednesday, May 31, 2023, 17:43 (126 days ago) @ David Turell
A major cell machine described:
https://phys.org/news/2023-05-understudied-cell-division-nanomachine-revealed.html
"Researchers have revealed, at high-resolution, the structure of a human protein complex named SIN3B, which is a 'nanomachine' involved in regulating cell division. Cell division is a fundamental process for life which, if it becomes uncontrolled, can lead to cancer.
"The team also discovered several interaction sites within these proteins, which can be mutated in people with cancer.
"This is the first time the high-resolution structure of a human protein complex of this kind has been determined.
***
"The DNA is packaged up inside each cell in a structure known as chromatin, where it is wrapped around proteins called histones forming nucleosomes, which are like beads on a string.
***
"The histones have linear structures coming off them—these histone tails can undergo a process known as lysine acetylation, performed by histone acetyl transferase enzymes (HATs), which helps ensure the chromatin is ready for DNA replication, DNA repair and gene transcription. Other enzymes called histone deacetylases (HDACs) counteract the role of HATs—making the chromatin more compact thereby shutting down gene transcription.
***
"...in collaboration with Professor Jyoti Choudhary's group, at the ICR were able to determine the structure of SIN3B, which surrounds the HDAC enzyme—activating it and allowing it to recognize and deacetylate nucleosomes.
"The findings, published in the journal Nature Communications, show that SIN3B helps to recruit other proteins, called PHF12 and MORF4L1, which allow the nanomachine to bind to the histone tail so it can inhibit transcription.
"Beyond discovering how the nanomachine assembles and does its job in regulating cell division, the researchers also showed where mutations in the proteins can occur in cancer patients—these faults stop healthy processes that suppress uncontrolled cell division and cancer.
***
"'We've known about HDAC enzymes for 50 years, but we didn't know how they specifically target the histones involved in wrapping up the DNA in our cells into a compact package in the nucleus. It's hugely exciting to be able to see something for the first time that no one else has ever seen before.'"
Comment: the article has a picture of the giant structure. There are so many steps in cell reproduction, the mechanisms are irreducibly complex and must have been designed all at once. A giant enzyme is designed with exact amino acids in exact positions for proper function.
Biochemical controls: specialized retinal ganglion cells
by David Turell , Sunday, January 29, 2023, 17:10 (248 days ago) @ David Turell
In macaque retina:
https://www.sciencemagazinedigital.org/sciencemagazine/library/item/27_january_2023/407...
"Tiny pulses of electrochemical energy known as “spikes” underlie brain function, from sensation and cognition to engendering vigorous action or quiet reflection. But exactly what kind of messages do spikes transmit to, through, and from the brain? On page 376 of this issue, Liu et al. (1) show how spiking activity in a small set of neurons in the macaque monkey eye can inform the brain about the huge range of environmental illumination encountered across every 24-hour day-night cycle. Light detection by the eye can synchronize the body’s biological (or circadian) rhythms to this cycle, regulating essential functions such as sleep, attention, and energy expenditure. The authors found that unlike conventional photoreceptors (rods and cones, which show stereotyped responses across a limited range of background intensities), each time-of-day–detecting neuron signals a different range of photon flux, so that together the population can encode the vast intensity range from starlight to bright sunlight.
***
"Nerve signals serving the sense of sight are carried along the optic nerve to the brain on the extended processes of retinal output cells called ganglion cells. An important clue to understanding time-of-day coding came when a new ganglion cell type was identified in 2002 (6, 7). These ganglion cells, known as melanopsin cells, show intrinsic photosensitivity based on a melanopsin-initiated phototransduction cascade, and innervate brain centers that control circadian rhythms (6-10). Melanopsin belongs to a large family of light-sensitive opsins. In the eye, the best known are in rod and cone photoreceptors. By contrast, the melanopsin cells have many features in common with the rhabdomeric photoreceptors expressed in the eyes of invertebrates...They found that the monkey melanopsin cells have idiosyncratic irradiance response functions, with distinct cells showing activity peaks at different levels of absolute photon flux (called population-radiance encoding). Thus, the population of melanopsin cells work together to signal a larger range of intensity than can be covered by a single neuron rate code.
"Axonal recordings were previously used to show a similar population-coding mechanism in mouse retina (11). But the live immunotagging method developed by Liu et al. goes much further, allowing observations of phenomena such as multistable photoswitching in melanopsin cells. When rod and cone opsins absorb a photon, they fall into an inactive state, and the chromophore (light-absorbing molecule) 11-cis-retinal must pass through a multistep reactivation cascade involving transport out of, then back into, the photoreceptor. By contrast, the chromophore in melanopsin cells can be reversibly knocked into or out of active states by successive photon absorption. This and other features of melanopsin-based phototransduction extend the range of light intensity encoded by individual melanopsin cells.
***
"It is important to emphasize that the study by Liu et al. goes beyond simply reproducing in monkeys what has been previously found in mice. Mice and monkeys occupy distinct ecological and behavioral niches and, crucially, mice are primarily nocturnal whereas monkeys (and most humans) are primarily active during the day. This means that a common proximate mechanism (population-radiance encoding) drives distinct circadian behaviors, sending mice to hide and sleep at illumination levels where monkeys start to rise and begin their daily activity. Every physiological process in animal bodies undergoes circadian rhythms (13). The presence of common mechanisms for irradiance encoding across more than 70 million years of independent evolution indicates strong evolutionary pressure for tight control of circadian rhythms by accurate reporting of environmental illumination to the brain."
From the original article:
"Light regulates physiology, mood, and behavior through signals sent to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs). How primate ipRGCs sense light is unclear, as they are rare and challenging to target for electrophysiological recording. We developed a method of acute identification within the live, ex vivo retina. Using it, we found that ipRGCs of the macaque monkey are highly specialized to encode irradiance (the overall intensity of illumination) by blurring spatial, temporal, and chromatic features of the visual scene. We describe mechanisms at the molecular, cellular, and population scales that support irradiance encoding across orders-of-magnitude changes in light intensity. These mechanisms are conserved quantitatively across the ∼70 million years of evolution that separate macaques from mice."
Comment: time of day changes ambient light and affects our biological diurnal rhythms. These are specially designed neurons to fit a specific necessary function of adaptation.
Biochemical controls: potassium regulation
by David Turell , Monday, January 30, 2023, 23:58 (247 days ago) @ David Turell
Both too low and too high can kill:
https://www.sciencedaily.com/releases/2023/01/230130090355.htm
"Potassium, a common mineral abundant in food like bananas and leafy greens, is essential to normal cellular function. It helps the cardiac muscle work correctly and aids in the transmission of electrical signals within cells.
"Using existing biological data, researchers at the University of Waterloo built a mathematical model that simulates how an average person's body regulates potassium, both in times of potassium depletion and during potassium intake. Because so many foods contain abundant potassium, our bodies constantly store, deploy, and dispose of potassium to maintain healthy levels -- a process known as maintaining potassium homeostasis. Understanding potassium homeostasis is essential in helping diagnose the source of the problem when something goes wrong -- for example, when kidney disease or medication leads to dysregulation.
***
"The model could be used for a virtual patient trial, allowing researchers to generate dozens of patients and then predict which ones would have hyper- or hypokalemia based on different controls.
"'A lot of our models are pieces of a bigger picture," said Anita Layton, professor of applied mathematics and Canada 150 Research Chair in mathematical biology and medicine. "This model is one new and exciting piece in helping us understand how our incredibly complex internal systems work."
"The model is especially exciting because it allows scientists to test something called the muscle-kidney cross-talk signal hypothesis. Scientists have hypothesized that skeletal muscles, which are responsible for most of the potassium storage in the body, can directly signal to the kidneys that it's time to excrete excess when too much potassium is stored, and vice versa. When the math researchers tested the hypothesis in their model, it more accurately reflected existing biological data regarding potassium homeostasis, suggesting that muscle-kidney cross talk might be an essential piece in the puzzle of potassium regulation."
Comment: potassium is a key intracellular constituent while sodium is in higher concentration outside cells. Potassium is stored largely in muscle cells as the article
notes. Feedback loops manage the controls both at the cellular and renal levels. These controls cannot be evolved stepwise, but must be designed because they are irreducibly complex.
Biochemical controls: photosynthesis in algae
by David Turell , Wednesday, February 01, 2023, 16:03 (245 days ago) @ David Turell
Irreducibly complex:
https://phys.org/news/2023-02-elucidate-enigmatic-chloroplast-protein-machinery.html
"Chloroplasts of algae and plants are the cellular engines that convert solar energy into chemical energy through photosynthesis. These organelles, bounded by an envelope with two membranes, contain their own genome whose expression is tightly coordinated with that of the nuclear genome. The majority of chloroplast proteins are encoded by nuclear genes, translated in the cytosol as precursor proteins containing a transit sequence at their amino terminus that serves as the entry ticket into chloroplasts.
"Protein import into chloroplasts is mediated by two membrane protein complexes called TOC and TIC in the outer and inner envelope membrane, respectively. These complexes play a key role in chloroplast biogenesis, in the assembly of the photosynthetic apparatuses and in various metabolic pathways. The different protein subunits of TOC and TIC have been identified and characterized, and TOC and TIC have been revealed to form a supercomplex together. However, how different proteins of TOC and TIC assemble together to form the channels for protein translocation across the chloroplast envelope membranes is unclear, and the protein translocation pathways within TOC and TIC remain elusive.
***
"The researchers elucidated the supramolecular architecture of the TOC-TIC supercomplex through cryo-electron microscopy.
"Thirteen different protein subunits in this supercomplex were discovered. With the exception of Tic214 encoded by the chloroplast genome, all the other subunits are nuclear encoded. They are assembled into the TOC complex in the outer membrane, the intermembrane space complex (ISC) and the TIC complex in the inner membrane. Remarkably, it was found that the largest membrane protein Tic214 spans the inner membrane, the intermembrane space and the outer membrane, linking the other protein subunits like a bridge and most likely also acting as a scaffold.
"The TOC complex in the outer membrane is mainly composed of Toc34, Toc90 and Toc75, flanked on the Toc90 side by the Ctap4-Ctap3 complex. A hybrid barrel-shaped channel is formed by Toc90 and Toc75 on the outer membrane. The channel contains an entrance on the cytosolic side and two exits opening toward the intermembrane space, as well as a lateral gate facing the lipid bilayer. A phytic acid (also known as inositol hexaphosphate/InsP6) molecule intercalates at the interface between Toc90 and Tic214, stabilizing their assembly like a wedge.
"The intermembrane-space domain of Tic214, Tic100, Tic56, Ctap3 and Ctap5 intertwine with each other to form a tower-like structure connecting TOC with TIC. In the inner membrane, the membrane-embedded domains of Tic214, Tic20, Ctap5 and three small subunits (named Simp1, Simp2 and Simp3) form the TIC complex. Four lipid molecules serve to stabilize the assembly of a funnel-like channel located at the interface between Tic214 and Tic20 and prevent the channel from leaking.
"Based on the structural data, the researchers analyzed in detail the features of the pores inside the TOC and TIC channels. They were able to predict the interactions between the transit peptide and the TIC complex through molecular dynamics simulation."
Comment: in a natural form of evolution all of these proteins must be formed and then put together in a combination that produces photosynthesis. Each early step must be functional in some accepted way to survive. This is irreducible complexity and must appear all at once so It must be designed.
Biochemical controls: photosynthesis in phytoplankton
by David Turell , Friday, June 02, 2023, 19:13 (124 days ago) @ David Turell
New discoveries:
https://www.sciencedaily.com/releases/2023/05/230531150117.htm
"Described as "groundbreaking" by a team of researchers at UC San Diego's Scripps Institution of Oceanography, this previously unknown process accounts for between 7% to 25% of all the oxygen produced and carbon fixed in the ocean. When also considering photosynthesis occuring on land, researchers estimated that this mechanism could be responsible for generating up to 12% of the oxygen on the entire planet.
***
"The new study, published May 31 in the journal Current Biology, identifies how a proton pumping enzyme (known as VHA) aids in global oxygen production and carbon fixation from phytoplankton.
***
"'Over millions of years of evolution, these small cells in the ocean carry out minute chemical reactions, in particular to produce this mechanism that enhances photosynthesis, that shaped the trajectory of life on this planet."
***
"Previous research in the Tresguerres Lab has worked to identify how VHA is used by a variety of organisms in processes critical to life in the oceans. This enzyme is found in nearly all forms of life, from humans to single-celled algae, and its basic role is to modify the pH level of the surrounding environment.
***
"Looking at this previous research, Yee wondered how the VHA enzyme was being used in phytoplankton. He set out to answer this question by combining high-tech microscopy techniques in the Tresguerres Lab and genetic tools developed in the lab of the late Scripps scientist Mark Hildebrand, who was a leading expert on diatoms and one of Yee's co-advisors.
"Using these tools, he was able to label the proton pump with a fluorescent green tag and precisely locate it around chloroplasts, which are known as "organelles" or specialized structures within diatom cells. The chloroplasts of diatoms are surrounded by an additional membrane compared to other algae, enveloping the space where carbon dioxide and light energy are converted into organic compounds and released as oxygen.
"We were able to generate these images that are showing the protein of interest and where it is inside of a cell with many membranes," said Yee. "In combination with detailed experiments to quantify photosynthesis, we found that this protein is actually promoting photosynthesis by delivering more carbon dioxide, which is what the chloroplast uses to produce more complex carbon molecules, like sugars, while also producing more oxygen as a by-product."
"Once the underlying mechanism was established, the team was able to connect it to multiple aspects of evolution. Diatoms were derived from a symbiotic event between a protozoan and an algae around 250 million years ago that culminated into the fusing of the two organisms into one, known as symbiogenesis. The authors highlight that the process of one cell consuming another, known as phagocytosis, is widespread in nature. Phagocytosis relies on the proton pump to digest the cell that acts as the food source. However, in the case of diatoms, something special occurred in which the cell that was eaten didn't get fully digested.
"'Instead of one cell digesting the other, the acidification driven by the proton pump of the predator ended up promoting photosynthesis by the ingested prey," said Tresguerres. "Over evolutionary time, these two separate organisms fused into one, for what we now call diatoms.'"
Not all algae have this mechanism, so the authors think that this proton pump has given diatoms an advantage in photosynthesis. They also note that when diatoms originated 250 million years ago, there was a big increase in oxygen in the atmosphere, and the newly discovered mechanism in algae might have played a role in that.
The majority of fossil fuels extracted from the ground are believed to have originated from the transformation of biomass that sank to the ocean floor, including diatoms, over millions of years, resulting in the formation of oil reserves. The researchers are hopeful that their study can provide inspiration for biotechnological approaches to improve photosynthesis, carbon sequestration, and biodiesel production.
Comment: Photosynthesis is a magical process converting light into oxygen as a byproduct. It's appearance is not through chance, is it?
Biochemical controls: controls of cell death (apoptosis)
by David Turell , Friday, June 02, 2023, 21:04 (124 days ago) @ David Turell
Cancer can happen during this process. It has a control:
https://medicalxpress.com/news/2023-06-scientists-reveal-cellular-cancer.html
"Apoptosis is essential for human life, and its disruption can cause cancerous cells to grow and not respond to cancer treatment. In healthy cells, it is regulated by two proteins with opposing roles known as Bax and Bcl-2.
"The soluble Bax protein is responsible for the clearance of old or diseased cells, and when activated, it perforates the cell mitochondrial membrane to form pores that trigger programmed cell death. This can be offset by Bcl-2, which is embedded within the mitochondrial membrane, where it acts to prevent untimely cell death by capturing and sequestering Bax proteins.
"In cancerous cells, the survival protein Bcl-2 is overproduced, leading to uninhibited cell proliferation. While this process has long since been understood to be important to the development of cancer however, the precise role of Bax and the mitochondrial membrane in apoptosis has been unclear until now.
***
"By using time-resolved neutron reflectometry in combination with surface infrared spectroscopy in the ISIS biolab, they were able to see that this pore creation occurred in two stages. Initial fast adsorption of Bax onto the mitochondrial membrane surface was followed by a slower formation of membrane-destroying pores and Bax-lipid clusters, which occurred simultaneously. This slower perforation process occurred on timescales of several hours, comparable to cell death in vivo.
"This is the first time that scientists have found direct evidence of the involvement of mitochondrial lipids during membrane perturbing in cell death initiated by Bax proteins.
"Dr. Luke Clifton continues, "As far as we can tell, this mechanism by which Bax initiates cell death is previously unseen. Once we know more about the interplay between Bax and Bcl-2 and how it relates to this mechanism, we'll have a more complete picture of a process that is fundamental to human life. This work really shows the capabilities of neutron reflectometry in structural studies on membrane biochemistry."
"The finding builds on previous studies by the team on the molecular mechanism of membrane-bound Bcl-2 to inform a more complete understanding of the early stages of apoptosis.
"Professor Gerhard Gröbner, University of Umeå scientist and and co-lead author says, "The unique findings here will not only have a significant impact in the field of apoptosis research but will also open gateways for exploring Bax and its relatives as interesting targets in cancer therapy such as by tuning up their cell-killing potential."
"Future research is planned at ISIS to further elucidate the molecular mechanism of apoptosis and in particular, to characterize the interplay between Bax and Bcl-2. It is hoped that this will yield insights which will open new avenues of research to continue to develop our understanding of the cellular processes necessary for human life."
Comment: raid precise action by Bax and Bc1-2 closes any loophole for cancer changes to sneak in. This mechanism shows God appreciated the chances for cancer. dhw's no-nothing God would not know this could happen and wouldn't have developed this blocking mechanisms.
Biochemical controls: photosynthesis from one photon
by David Turell , Wednesday, June 14, 2023, 17:26 (112 days ago) @ David Turell
Finally proven:
https://www.sciencenews.org/article/one-photon-photosynthesis-light
"For photosynthesis, one photon is all it takes.
"Only a single particle of light is required to spark the first steps of the biological process that converts light into chemical energy, scientists report June 14 in Nature.
"'While scientists have long assumed that the reactions of photosynthesis begin upon the absorption of just one photon, that hadn’t yet been demonstrated, says physical chemist Graham Fleming, of the University of California, Berkeley. He and colleagues decided “we would just look to see was it really true that one photon was enough to start the whole thing off.”
***
"Many laboratory experiments on photosynthesis use lasers, much more powerful light sources, to kick off the reactions. Instead, Graham and colleagues used a source of light that produces just two photons at a time. One photon served as a herald, going off to a detector to let researchers know when two photons were released. The other photon went into a solution containing photon-absorbing structures from the photosynthetic bacterium Rhodobacter sphaeroides. These structures, called light-harvesting 2 complexes, or LH2, are made up of two rings of bacteriochlorophyll and other molecules.
"In a normal photosynthesis reaction, LH2 absorbs a photon and passes its energy to another LH2 complex, and then another, like a game of hot potato. Eventually the energy reaches another type of ring, called the light-harvesting 1 complex, or LH1, which then passes it to the reaction center where the energy is finally converted into a form that the bacterium can use.
"In the experiment, there was no LH1, so the LH2 instead emitted a photon of a different wavelength than the first, a sign that energy had been transferred from the first ring of LH2 to the second, a first step of photosynthesis. The researchers detected that second photon, and by comparing the detection times to those of the initial herald photons, confirmed that the LH2 needed to absorb only one photon to kick things off.
"Plants and bacteria use different processes for photosynthesis, but the initial steps are similar enough that in plants, too, a single photon would set off the initial steps, Fleming says. However, in plants, multiple independently absorbed photons are needed in order to complete the reaction."
Comment: this basic process has such intricate parts in the stepwise way it works, it is irreducibly complex and must have been designed. dhw's experimenting God would never have produced this result.
Biochemical controls: photosynthesis from one photon
by David Turell , Monday, July 03, 2023, 22:49 (93 days ago) @ David Turell
Another study of photon usage:
https://phys.org/news/2023-07-chemists-photosynthetic-light-harvesting-efficient.html
"When photosynthetic cells absorb light from the sun, packets of energy called photons leap between a series of light-harvesting proteins until they reach the photosynthetic reaction center. There, cells convert the energy into electrons, which eventually power the production of sugar molecules.
"This transfer of energy through the light-harvesting complex occurs with extremely high efficiency: Nearly every photon of light absorbed generates an electron, a phenomenon known as near-unity quantum efficiency.
"A new study from MIT chemists offers a potential explanation for how proteins of the light-harvesting complex, also called the antenna, achieve that high efficiency. For the first time, the researchers were able to measure the energy transfer between light-harvesting proteins, allowing them to discover that the disorganized arrangement of these proteins boosts the efficiency of the energy transduction.
"'In order for that antenna to work, you need long-distance energy transduction. Our key finding is that the disordered organization of the light-harvesting proteins enhances the efficiency of that long-distance energy transduction," says Gabriela Schlau-Cohen, an associate professor of chemistry at MIT and the senior author of the new study.
***
"For this study, the researchers embedded two versions of the primary light-harvesting protein found in purple bacteria, known as LH2 and LH3, into their nanodiscs. LH2 is the protein that is present during normal light conditions, and LH3 is a variant that is usually expressed only during low light conditions.
***
"Because LH2 and LH3 absorb slightly different wavelengths of light, it is possible to use ultrafast spectroscopy to observe the energy transfer between them. For proteins spaced closely together, the researchers found that it takes about 6 picoseconds for a photon of energy to travel between them. For proteins farther apart, the transfer takes up to 15 picoseconds.
"Faster travel translates to more efficient energy transfer, because the longer the journey takes, the more energy is lost during the transfer.
"'When a photon gets absorbed, you only have so long before that energy gets lost through unwanted processes such as nonradiative decay, so the faster it can get converted, the more efficient it will be," Schlau-Cohen says.
"The researchers also found that proteins arranged in a lattice structure showed less efficient energy transfer than proteins that were arranged in randomly organized structures, as they usually are in living cells.
"'Ordered organization is actually less efficient than the disordered organization of biology, which we think is really interesting because biology tends to be disordered. This finding tells us that that may not just be an inevitable downside of biology, but organisms may have evolved to take advantage of it," Schlau-Cohen says."
Comment: this degree of efficiency is amazing, and could not have developed by chance.
Biochemical controls: photosynthesis from one photon
by David Turell , Wednesday, July 05, 2023, 16:10 (91 days ago) @ David Turell
Another view:
https://www.quantamagazine.org/microbes-gained-photosynthesis-superpowers-from-a-proton...
"Researchers knew that certain classes of phytoplankton — diatoms, dinoflagellates and coccolithophores — stand out for their exceptional photosynthetic abilities. Those cells are extremely proficient at absorbing carbon dioxide from their environment and directing it to their chloroplasts for photosynthesis, but the details of why they are so good at it haven’t been very clear. A feature unique to those three groups of phytoplankton, however, is that they have an extra membrane around their chloroplasts.
"Daniel Yee, the lead author on the new study, was studying diatoms for his doctorate at the Scripps Institution of Oceanography at the University of California, San Diego. Photosynthesis wasn’t his focus; he sought to understand how diatoms regulate their internal acidity to help with nutrient storage and to build their tough silica cell wall. But he kept noticing the unique additional membrane around their chloroplasts.
"He learned that the extra membrane was widely regarded by researchers as a remnant of an ancient, failed act of digestion. Scientists hypothesized that about 200 million years ago, a predatory protozoan tried to feast on a single-celled photosynthetic alga. It enveloped the resilient alga in a membrane structure called a food vacuole to digest it, but for unknown reasons, digestion did not occur. Instead, the alga survived and became a symbiotic partner to the protozoan, feeding it the fruits of its photosynthesis. This partnership deepened over the generations until the new two-in-one organism evolved into the diatoms we know today. But the extra layer of membrane that had been a food vacuole never disappeared.
***
"Using a combination of molecular biology techniques, Yee and his team confirmed that the extra membrane around the phytoplankton chloroplast does contain an active, functional proton pump — one called VHA that often serves a digestive role in food vacuoles. They even fused the proton pump to a fluorescent protein so that they could watch it work in real time. Their observations supported the endosymbiotic theory of how the diatoms acquired the extra membrane around their chloroplasts.
***
"Further work helped them understand that the pump enhanced photosynthesis by concentrating carbon near chloroplasts. The pump transferred protons from the cytoplasm to the compartment between the extra membrane and the chloroplast. The increased acidity in the compartment caused more carbon (in the form of bicarbonate ions) to diffuse into the compartment to neutralize it. Enzymes converted the bicarbonate back into carbon dioxide, which was then conveniently near the chloroplast’s carbon-fixing enzymes.
"Using statistics on the distribution of the diatoms and other phytoplankton with the extra membrane throughout the global ocean, the researchers extrapolated that this boost in efficiency from the VHA membrane protein accounts for almost 12% of Earth’s atmospheric oxygen. It also contributes between 7% and 25% of all the oceanic carbon fixed each year. That’s at least 3.5 billion tons of carbon — almost four times as much as the global aviation industry emits annually. At the high end of the researchers’ estimate, VHA could be responsible for tying up as much as 13.5 billion tons of carbon a year."
Comment: without this amazingly complex process we would not be here.
Biochemical controls: plant root growth factors
by David Turell , Saturday, July 08, 2023, 18:23 (88 days ago) @ David Turell
Specific gene controls studied:
https://phys.org/news/2023-07-uncovers-secrets-regeneration.html
"Plants have the unique ability to regenerate entirely from a somatic cell, i.e., an ordinary cell that does not typically participate in reproduction. This process involves the de novo (or new) formation of a shoot apical meristem (SAM) that gives rise to lateral organs, which are key for the plant's reconstruction.
"At the cellular level, SAM formation is tightly regulated by either positive or negative regulators (genes/protein molecules) that may induce or restrict shoot regeneration, respectively. But which molecules are involved? Are there other regulatory layers that are yet to be uncovered?
***
"They demonstrated how the WUSCHEL-RELATED HOMEOBOX 13 (WOX13) gene and its protein can promote the non-meristematic (non-dividing) function of callus cells by acting as a transcriptional (RNA-level) repressor, thereby impacting regeneration efficiency.
***
"Previous studies from the team had already established the role of WOX13 in tissue repair and organ adhesion after grafting. Hence, they first tested the potential role of this gene in the control of shoot regeneration in a wox13 Arabidopsis mutant (plant with dysfunctional WOX13) using a two-step tissue culture system.
"Phenotypic and imaging analysis revealed that shoot regeneration was accelerated (three days faster) in plants lacking WOX13, and slower when WOX13 expression was induced. Moreover, in normal plants, WOX13 showed locally reduced expression levels in SAM. These findings suggest that WOX13 can negatively regulate shoot regeneration.
"To validate their findings, the researchers compared the wox13 mutants and wild-type (normal) plants using RNA-sequencing at multiple time points. The absence of WOX13 did not considerably alter Arabidopsis gene expression under callus-inducing conditions. However, shoot-inducing conditions significantly enhanced the alterations induced by the wox13 mutation, leading to an upregulation of shoot meristem regulator genes.
"Interestingly, these genes were suppressed within 24 hours of WOX13 overexpression in mutant plants. Overall, they found that WOX13 inhibits a subset of shoot meristem regulators while directly activating cell wall modifier genes involved in cell expansion and cellular differentiation. Subsequent Quartz-Seq2-based single cell RNA sequencing (scRNA-seq) confirmed the key role of WOX13 in specifying the fate of pluripotent callus cells.
"This study highlights that unlike other known negative regulators of shoot regeneration, which only prevent the shift from callus toward SAM, WOX13 inhibits SAM specification by promoting the acquisition of alternative fates. It achieves this inhibition through a mutually repressive regulatory circuit with the regulator WUS, promoting the non-meristematic cell fate by transcriptionally inhibiting WUS and other SAM regulators and inducing cell wall modifiers.
"In this way, WOX13 acts as a major regulator of regeneration efficiency. "Our findings show that knocking out WOX13 can promote the acquisition of shoot fate and enhance shoot regulation efficiency. This means that WOX13 knockout can serve as a tool in agriculture and horticulture and boost the tissue culture-mediated de novo shoot regeneration of crops," concludes Ikeuchi."
Comment: I wonder why this set of controls slowed growth of root tips. There may be a missing factor in this mix. The final result in purposeful evolution is always the correct one, and we will interfere with it. Designed, obviously, not by chance.
Biochemical controls: immune memory
by David Turell , Wednesday, July 12, 2023, 20:30 (84 days ago) @ David Turell
Requires a fast response:
https://www.sciencedaily.com/releases/2023/07/230711133218.htm
"The immune system is one of the most complex parts of our body. It keeps us healthy by getting rid of parasites, viruses or bacteria, and by destroying damaged or cancer cells. One of its most intriguing abilities is its memory: upon first contact with a foreign component (called "antigens" in scientific jargon) our adaptive immune system takes around two weeks to respond, but responses afterwards are much faster, as if the cells "remembered" the antigen. But how is this memory attained? In a recent publication, a team of researchers...provides new clues on immune memory using state-of-the-art methodologies.
***
"...first-author Anne Onrust-van Schoonhoven and colleagues compared the response of immune cells that had never been in contact with an antigen (called naïve cells) with cells previously exposed to antigen (memory cells) and sort of knew it. They focused on the differences in the epigenetic control of the cellular machinery and the nuclear architecture of the cells, two mechanisms that could explain the quick activation pattern of memory cells.
***
"The results of the research team revealed a particular epigenetic signature in memory cells, resulting in the rapid activation of a crucial set of genes compared to naive cells. These genes were much more accessible to the cellular machinery, in particular to a family of transcription factors called AP-1. To put it into a racing context: these genes have been warming-up ever since the cell's first contact with the antigen.
"However, this epigenetic signature was just the tip of the iceberg. It is known that the position of the DNA in the nucleus is not random and reflects the cell's activation state. The researchers found that, indeed, the 3D distribution of DNA in the nucleus is different between naïve and memory immune cells. Key genes for the early immune response are grouped together and under the influence of the same regulatory regions, called enhancers. Keeping with the racing metaphor, the genes are not only warmed-up, but also gathered together at the starting line.
"Although most of the research has focused on healthy cells, the scientific team wondered whether any of the mechanisms found could, when altered, explain actual diseases in which the immune system plays an important role. To address this question, they analyzed immune cells from chronic asthma patients and found that the circuits identified as key for an early and strong immune response were overactivated."
Comment: the library of antibody responses is built slowly, but expressed rapidly when a challenge is met. A great design
Biochemical controls:photosynthesis roughly 100% efficient
by David Turell , Sunday, July 16, 2023, 00:58 (81 days ago) @ David Turell
At a quantum level from disordered biology:
https://bigthink.com/starts-with-a-bang/photosynthesis-100-efficient-quantum-physics/?u...
"In terms of energy, the “holy grail” of any physical system is 100% efficiency. It’s a near-impossible goal under most conditions, as from the moment any form of energy first gets transferred into a system, it inevitably gets lost to a variety of factors — heat, collisions, chemical reactions, etc. — before finally accomplishing the ultimate task it was designed for.
***
"But nature has provided us with a very surprising exception to that rule: plants. The humble plant, along with other, more primitive photosynthetic organisms, absorbs a fraction of sunlight at specific (blue and red) wavelengths to convert that light (photon) energy into sugars via the complex process of photosynthesis. Yet somehow, despite obeying none of the above physical conditions, nearly 100% of that absorbed energy gets converted into electron energy, which then creates those sugars via photosynthesis. For as long as we’ve known about the underlying chemical pathway of photosynthesis, this has been an unsolved problem. But thanks to the interface of quantum physics, chemistry, and biology, we may finally have the answer, and biological disorder is the key.
***
"The chlorophyll found in plants is only capable of absorbing and using sunlight over two particular narrow wavelength ranges: blue light that peaks at around 430 nanometers in wavelength and red light that peaks around 662 nanometers in wavelength. Chlorophyll a is the molecule that makes photosynthesis possible, and is found in all photosynthetic organisms: plants, algae, and cyanobacteria among them. (Chlorophyll b, another light-absorbing and photosynthesizing molecule found only in some photosynthetic organisms, has a different set of wavelength peaks.)
***
"if we restrict ourselves to looking at only the individual photons that can excite the chlorophyll a molecule — photons at or near the two absorption peaks of chlorophyll a — the red-wavelength photons are around 80% efficient, while the blue-wavelength photons are over 95% efficient: close to that perfect, 100% efficiency after all.
***
"The puzzle in all of this is why, for every photon that gets absorbed in that very first step, approximately 100% of those photons wind up producing excited electrons at the end of the last step? In terms of efficiency, there are really no known naturally occurring physical systems that behave in this manner. Yet somehow, photosynthesis does.
"Under most laboratory circumstances, if you want to make an energy transfer 100% efficient, you have to specially prepare a quantum system in a very particular way... And you need to impose as close to “lossless” conditions as possible, where no energy gets lost due to the internal vibrations or rotations of particles, such as propagating excitations known as phonons.
"But in the process of photosynthesis, absolutely zero of these conditions are present. The light that comes in is plain old white sunlight: composed of a wide variety of wavelengths, where no two photons have exactly the same energy and momentum. The absorptive system isn’t ordered in any way, as the distances between the various molecules isn’t fixed in a lattice but rather varies tremendously: on scales of several nanometers between even adjacent molecules. And these molecules are all free to both vibrate and rotate; there are no special conditions that prevent these motions from occurring.
***
"It’s important to remember that, unlike in most physical laboratory systems, there isn’t an “organization” to the protein network in biological systems; they’re located and spaced irregularly from one another in what’s known as a heterogeneous fashion, where each protein-protein distance is different from the last.
***
"A key finding of this research is that these light-harvesting proteins can only very efficiently transfer this energy over long distances because of the irregular and disordered spacing of proteins within the purple bacteria themselves. If the arrangement was regular, periodic, or organized in a conventional way, this long-distance, high-efficiency energy transport could not occur.
***
"And this is what the researchers actually found in their studies. If the proteins were arranged in a periodic lattice structure, the energy transfer was less efficient than if the proteins were arranged in a “randomly organized” pattern, the latter of which is far more representative of how protein arrangements normally occur within living cells.
***
"In other words, what we normally consider a “bug” of biology, that biological systems are inherently disordered by many metrics, may actually be the key to how photosynthesis occurs at all in nature.
***
"We normally think of quantum physics as only being relevant for the simplest of systems. In truth, however, it’s the underlying explanation behind every non-gravitational phenomenon in our macroscopic world: from how particles bind together to form atoms to how atoms join to make molecules to the chemical reactions that occur between atoms and molecules to how photons are absorbed and emitted by those atoms and molecules."
Comment: an amazing deigned system, not by chance. Al the complex methodology omitted.
Biochemical controls: oxygen without photosynthesis
by David Turell , Monday, July 17, 2023, 16:52 (79 days ago) @ David Turell
By a different system deep underground:
https://www.quantamagazine.org/underground-cells-make-dark-oxygen-without-light-20230717/
"In groundwater reservoirs 200 meters below the fossil fuel fields of Alberta, Canada, they discovered abundant microbes that produce unexpectedly large amounts of oxygen even in the absence of light. The microbes generate and release so much of what the researchers call “dark oxygen” that it’s like discovering “the scale of oxygen coming from the photosynthesis in the Amazon rainforest,” said Karen Lloyd, a subsurface microbiologist at the University of Tennessee who was not part of the study. The quantity of the gas diffusing out of the cells is so great that it seems to create conditions favorable for oxygen-dependent life in the surrounding groundwater and strata.
“It is a landmark study,” said Barbara Sherwood Lollar, a geochemist at the University of Toronto who was not involved in the work. Past research has often looked at mechanisms that could produce hydrogen and some other vital molecules for underground life, but the generation of oxygen-containing molecules has been largely overlooked because oxygen seems so wedded to photosynthesis and the presence of light. Until now, “no study has pulled it all together quite like this one,” she said.
"The new study looked at deep aquifers in the Canadian province of Alberta, which has such rich deposits of underground tar, oil sands and hydrocarbon that it has been dubbed “the Texas of Canada.”
***
"The researchers started identifying the microbes in the samples, using molecular tools to spot their telltale marker genes. A lot of them were methanogenic archaea — simple, single-celled microbes that produce methane after consuming hydrogen and carbon oozing out of rocks or in decaying organic matter. Also present were many bacteria that feed on the methane or on minerals in the water. (my bold)
"What didn’t make sense, however, was that many of the bacteria were aerobes — microbes that require oxygen to digest methane and other compounds. How could aerobes thrive in groundwaters that should have no oxygen, since photosynthesis is impossible? But chemical analyses found a lot of dissolved oxygen in the 200-meter-deep groundwater samples too.
***
"While working in a lab in the Netherlands in the late 2000s, Strous noticed that a type of methane-feeding bacteria often found in lake sediments and wastewater sludges had a strange way of life. Instead of taking in oxygen from its surroundings like other aerobes, the bacteria created its own oxygen by using enzymes to break down the soluble compounds called nitrites (which contain a chemical group made of nitrogen and three oxygen atoms). The bacteria used the self-generated oxygen to split methane for energy.
"When microbes break down compounds this way, it’s called dismutation. Until now, it was thought to be rare in nature as a method for generating oxygen. Recent laboratory experiments involving artificial microbe communities, however, revealed that the oxygen produced by dismutation can leak out of the cells and into the surrounding medium to the benefit of other oxygen-dependent organisms, in a kind of symbiotic process. Ruff thinks that this could be what’s enabling entire communities of aerobic microbes to thrive in the groundwater, and potentially in the surrounding soils as well.
"The finding fills a crucial gap in our understanding of how the huge subterranean biosphere has evolved, and how dismutation contributes to the cycle of compounds moving through the global environment. The mere possibility that oxygen is present in groundwater “changes our understanding about the past, present and future of subsurface,” said Ruff, who is now an assistant scientist at the Marine Biological Laboratory in Woods Hole, Massachusetts.
***
"Regardless of how important dismutation turns out to be elsewhere in the universe, Lloyd is astonished by how much the new findings defy preconceived notions about life’s needs, and by the scientific cluelessness they reveal about one of the planet’s biggest biospheres. “It’s as if we have had egg on our face all along,” she said."
Comment: life is everywhere, as amazing as it seems. Note my bold. Ancient Archaea from the start of life showed the way to make oxygen.
Biochemical controls: expanding bacterial walls
by David Turell , Thursday, July 20, 2023, 17:43 (76 days ago) @ David Turell
Crack open and fill up:
https://phys.org/news/2023-07-achilles-heel-bacterial-cell-wall.html
"The bacterial cell wall must be constantly remodeled in order to grow and divide. This involves the close coordination of lytic enzymes and peptidoglycan synthesis. In their study published in Nature Communications, researchers led by Martin Thanbichler have now found that a central regulator can control completely different classes of autolysins.
***
"Most bacterial species synthesize a semi-rigid cell wall surrounding the cytoplasmic membrane, whose main component, peptidoglycan, forms a dense meshwork that encases the cell. In addition to its protective role, the cell wall also serves as a means to generate specific cell shapes, such as spheres, rods, or spirals, thus facilitating motility, surface colonization, and pathogenicity.
"The presence of a cell wall presents its own challenges: cells must constantly remodel it in order to grow and divide. To do this, they must very carefully make tears in the wall to allow it to expand and change, while quickly mending the gaps with new material to prevent it from collapsing.
"This cell wall remodeling process involves the cleavage of bonds by lytic enzymes, also known as autolysins, and the subsequent insertion of new cell wall material by peptidoglycan synthases. The activities of these two antagonistic groups of proteins must be closely coordinated to prevent weak spots in the peptidoglycan layer that lead to cell lysis and death.
***
"Analysis of potential autolysin regulators by co-immunoprecipitation screening and in vitro protein-protein interaction assays has revealed that a factor called DipM plays a pivotal role in bacterial cell wall remodeling. This key regulator, a soluble periplasmic protein, surprisingly interacts with several classes of autolysins as well as a cell division factor, showing a promiscuity that was previously unknown for this type of regulator.
"DipM was able to stimulate the activity of two peptidoglycan-cleaving enzymes with completely different activities and folding, making it the first identified regulator that can control two classes of autolysins. Notably, the results also indicate that DipM uses a single interface to interact with its various targets.
"'Disruption of DipM leads to the loss of regulation at various points of the cell wall remodeling and division process and ultimately kills the cell," says doctoral student Adrian Izquierdo Martinez, first author of the study. "Its proper function as a coordinator of autolysin activity is thus critical for proper cell shape maintenance and cell division in C. crescentus."
"The comprehensive characterization of DipM revealed a novel interaction network, including a self-reinforcing loop that connects lytic transglycosylases and possibly other autolysins to the core of the cell division apparatus of C. crescentus, and very likely also other bacteria. Thus, DipM coordinates a complex autolysin network whose topology greatly differs from that of previously studied autolysin systems.
"Martin Thanbichler points out, "The study of such multi-enzyme regulators, whose malfunction affects several cell wall-related processes at the same time, not only helps us to understand how the cell wall responds to changes in the cell or the environment. It can also contribute to the development of new therapeutic strategies that combat bacteria by disrupting several autolytic pathways simultaneously.' "
Comment: the earliest bacterial forms had to have had this mechanism to expand its cell wall and divide or the species would not have reproduced and survive. This degree of complexity is ancient and must have been designed when the first bacteria were formed.
Biochemical controls: parasites control hosts
by David Turell , Thursday, July 20, 2023, 18:05 (76 days ago) @ David Turell
while losing unneeded genes:
https://www.sciencedaily.com/releases/2023/07/230718164256.htm
"Parasitic hairworms manipulate the behavior of their hosts in what's sometimes called 'mind control.' A new study reveals another strange trait shared by different hairworm species: they're missing about 30% of the genes that researchers expected them to have. What's more, the missing genes are responsible for the development of cilia, the hair-like structures present in at least some of the cells of every other animal known.
***
"Hairworms are found all over the world, and they look like skinny strands of spaghetti, a couple inches long. Their simple bodies hint at their parasitic lifestyle -- they have no excretory, respiratory, or circulatory systems, and they spend almost their entire lives inside the bodies of other animals. "One of the coolest things, maybe the thing that they are most known for, is that they can affect the behavior of their hosts and make them do things that they wouldn't do otherwise," says Tauana Cunha, a postdoctoral researcher at Chicago's Field Museum.
"There are a few hundred species of freshwater hairworms. Their eggs hatch in water, and the hairworm larvae get eaten by tiny water-dwelling predators like mayfly larvae, which in turn get eaten by bigger, land-dwelling predators like crickets. After growing into adulthood inside of their new hosts' bodies, the hairworms manipulate the hosts' behavior, causing them to jump into water. There, the worms swim out of their hosts' butts and seek out mates, knotting themselves together, to begin the cycle anew. (There are also five species of hairworms that live in marine environments and parasitize water-dwelling creatures like lobsters, but it's not clear if those ones also have host manipulation capabilities -- there's no pressure for the worms to get back to the water, since the hosts already live there.)
***
"'What we found, which was very surprising, was that both hairworm genomes were missing about 30% of a set of genes that are expected to be present across basically all groups of animals," says Cunha.
"Results like that often make scientists wonder if they've made a mistake. But there was a connection between the missing genes in the two worm species. "The large majority of the missing genes were exactly the same between the two species. This was just implausible by chance," says Cunha.
***
"'Based on previous observations, it didn't seem like hairworms had any cilia, but we didn't really know for sure," says Cunha. "Now with the genomes, we saw that they actually lack the genes that produce cilia in other animals -- they don't have the machinery to make cilia in the first place."
"What's more, the fact that both the freshwater and marine hairworm species had lost the genes for cilia indicates that this evolutionary change happened in the deep past to the two species' common ancestor.
***
"Hairworms aren't the only parasites capable of "mind control" -- it's a behavior that's cropped up in protozoans like the organism responsible for toxoplasmosis, which reduces rodents' fear of cats, and in the fungus Ophiocordyceps, which manipulates ants into spreading the fungus's spores. While these organisms are only distantly related to hairworms, Cunha says that the new study could help scientists find common threads for how this behavior works. "By doing this comparative analysis across organisms in the future, we might be able to look for similarities. Or maybe these organisms evolved similar behaviors in completely different ways from each other," says Cunha."
Comment: no question parasites lose genes whose functions are handled by the host organism. The last paragraph above reviews all the previous articles presented here about parasitism and mind control.
Biochemical controls: making insulin
by David Turell , Tuesday, July 25, 2023, 18:02 (71 days ago) @ David Turell
A study in flies:
https://www.sciencedaily.com/releases/2023/07/230724122634.htm
"Studying insulin production in humans or mammals is difficult. In humans, the pancreas is situated behind the liver. It doesn't regenerate well, and it can't be sampled in live subjects. But in flies, their insulin cells are actually in their brains, function like neurons, and are physically accessible to researchers. In fruit flies, the researchers looked at a tag called RNA N-6 adenosine methylation, or m6A.
"To study the m6A tag, the researchers first identified the RNAs that have the tag. Then they labeled insulin cells with a fluorescent molecule, and used confocal microscopy to visualize how much insulin is produced by the insulin cell. They did this under two conditions: first, they knocked out the m6A enzyme, responsible for decorating the mRNA with m6A tags, in insulin cells. Second, they removed the m6A tags by using CRISPR, a technology used to edit DNA, to mutate the modified As.
In both cases, the flies' ability to produce insulin was greatly reduced.
"'We found that this photocopy of the DNA for insulin, this mRNA, had a specific tag that, when it is present, a ton of the insulin hormone is made," said Dus, associate professor of molecular, cellular and developmental biology. "But without the signal, flies had much less insulin and developed hallmarks of diabetes."
"This chemical tag is conserved -- or unchanged -- in fish, mice and humans.
"'So it's likely that insulin production is also regulated through this kind of mechanism in humans," Wilinski said. "There is an obesity and diabetes epidemic not just in the United States, but across the world. Our finding is another bit of evidence about how this disease happens."
"Dus says the discovery fleshes out the understanding of the biology of insulin and the physiology of diseases of energy homeostasis. Low levels of chemical tags have been observed in people with Type 2 diabetes. Restoring the levels of these tags may also help with combating diabetes and metabolic disease, she says."
Comment: every process in living cells depends upon specific biochemicals. We can identify them but we still do not know how the molecule achieves its purpose. Sucj specificity is not possible with any form of chance evolution.
Biochemical controls: molecular movements
by David Turell , Thursday, August 10, 2023, 18:52 (55 days ago) @ David Turell
The latest technique:
https://phys.org/news/2023-08-ultrafast-physics-biology-reveals-molecular.html
"Crystallography is a powerful technique in structural biology for taking 'snapshots' of how molecules are arranged. Over several large-scale experiments and years of theory work, the team behind the new study integrated this with another technique that maps vibrations in the electronic and nuclear configuration of molecules, called spectroscopy.
"Demonstrating the new technique at powerful X-ray laser facilities around the world, the team showed that when molecules within the protein that they studied are optically excited, their very first movements are the result of 'coherence.' This shows a vibrational effect, rather than motion for the functional part of the biological reaction that follows.
"This is important distinction, shown experimentally for the first time, highlights how the physics of spectroscopy can bring new insights to the classical crystallography methods of structural biology.
"Professor van Thor said, "Every process that sustains life is carried out by proteins, but understanding how these complex molecules do their jobs depends on learning the arrangement of their atoms—and how this structure changes—as they react.
***
"Members of the team have been working since 2009 at XFELs to use and understand the motions of reacting proteins on the femtosecond (one millionth of one billionth of a second) timescale, known as femtochemistry. Following excitation by a laser pulse, 'snapshots' of the structure are taken using X-rays. (my bold)
"Early success with this technique in 2016 resulted in a detailed picture of the light-induced change in a biological protein. However, researchers still needed to address a key question: what is the origin of the tiny molecular 'motions' on the femtosecond time scale directly after the first laser light pulse?
***
"The conclusion was that the ultrafast motions measured with exquisite accuracy on the picometer scale and femtosecond time scale do not belong to the biological reaction, but instead to vibrational coherence in the remaining ground state.
"This means that the molecules that are 'left behind' after the femtosecond laser pulse has passed dominate the motions that are subsequently measured, but only within the so-called vibrational coherence time.
'Professor van Thor said, "We concluded that for our experiment, also if coherent control was not included, the conventional time resolved measurement was in fact dominated by motions from the dark 'reactant' ground state, which are unrelated to the biological reactions that are triggered by the light. Instead, the motions correspond to what is traditionally measured by vibrational spectroscopy and have a very different, but equally important, significance." (my bold)
Comment: note my bolds. The movement of free-floating molecules is affected by the liquid environment in which they exist. dhw wants them completely controlled, but by 'what' or 'how' is totally unclear. Another answer to the theodicy problem.
Biochemical controls: FUBI's role
by David Turell , Saturday, August 12, 2023, 00:19 (54 days ago) @ David Turell
The first insights:
https://phys.org/news/2023-08-protein-factories-runhow-deubiquitinating-enzymes.html
"Scientists around Malte Gersch, research group leader has now gained first molecular insights into the machinery facilitating the Fubi-controlled maturation of a key protein of the ribosome, the cell's protein factory. With the help of a newly developed chemical tool kit, the researchers characterized how two deubiquitinating enzymes provide specific Fubi hydrolase activity and thereby moonlight as Fubi proteases in a two-tier manner.
"Fubi is produced by cells as a fusion protein with the ribosomal protein S30, and must be separated from S30 by proteases for functioning ribosomes. In immune cells, this by-product of ribosome production is utilized as a secreted signaling molecule, for example to locally reduce the activity of the maternal immune system in the uterus and to thus enable embryos to implant. How Fubi is specifically recognized by proteases and how they distinguish it from ubiquitin was previously unknown.
"Our team revealed how two deubiquitinating enzymes can also act as proteases of the ubiquitin-like protein Fubi and gained molecular insights into how this is possible in specific manner. This is noteworthy because, despite similarity between Ubiquitin and Ubiquitin-like proteins, the enzymes regulating them in humans are usually not the same.
"We show that this dual activity is specific to the two enzymes USP16 and USP36 and our crystallography studies mechanistically explain how this rare cross-reactivity is achieved. Surprisingly, unlike what is observed in cross-reactive enzymes from bacteria or viruses, we did not find any additional structural elements that facilitate the additional Fubi activity of these well characterized Ubiquitin proteases.
"Instead, Fubi recognition is mediated through a small cryptic motif on a complementary binding surface.
***
"Our work provides new molecular insights into how enzymes can have activities spanning multiple modification systems. Explaining how USP16 and USP36 play a role in ribosomal protein maturation expands our understanding of mechanisms regulating this critical cellular process.
"Fubi has primarily been studied by scientists from the immunology field, and more recently of the ribosome field, and our work approaching the topic with the Ubiquitin background complements these other works. Together all data converges into a two-tier model for Fubi processing.
"Owed to their rapid and reversible nature posttranslational modifications such as Ubiquitin and Ubiquitin-like proteins are critical regulators of virtually all cellular processes.
"Fubi has been linked to immunomodulatory functions and has been shown to modify proteins during immune stimulation responses. Understanding the exact role of Fubi in this process will expand our understanding of the how cells respond to immune signaling.
"Our insights into Fubi recognition allow for tuneable Fubi protease activity in cells and are thus paving the way for better understanding the cellular role of this enigmatic protein as a post-translational modification.
"In addition, we are using the probes to facilitate investigation into the molecular mechanism by which other proteins interact with Fubi. But first we will celebrate."
Comment: as usual, the new research provides increased knowledge of how complex the biology of life is in the interlocking molecular relationships. This is from an interview and I have simply given the answers. Such complexity is not by chance.
Biochemical controls: plant controls for gravity
by David Turell , Sunday, August 13, 2023, 23:08 (52 days ago) @ David Turell
Plant bodies up, roots down:
https://www.sciencedaily.com/releases/2023/08/230810141032.htm
"Plants orient their organs in response to the gravity vector, with roots growing towards gravity and shoots growing in the opposite direction. The movement of statoliths responding to the inclination relative to the gravity vector is employed for gravity sensing in both plants and animals. However, in plants, the statolith takes the form of a high-density organelle, known as an amyloplast, which settles toward gravity within the gravity sensing cell. Despite the significance of this gravity sensing mechanism, the exact process behind it has eluded scientists for over a century.
***
"In their earlier work, the team discovered that Arabidopsis LAZY1-LIKE (LZY) proteins play a crucial role in gravity signal transduction, with polar localization at the plasma membrane on the side of gravity. Nevertheless, the exact mechanism establishing this remarkable localization remained unknown.
"Through sophisticated live cell imaging techniques, including vertical stage microscopy and optical tweezers, the research team made a significant breakthrough. They found that LZYs not only localize at the plasma membrane near amyloplasts but also at the amyloplasts themselves. "The plasma membrane localization of LZYs surprised us, as it is generated by the close proximity of amyloplasts to the membrane," explained Takeshi Nishimura, Assistant Professor at NIBB and the first author of the study.
"'We demonstrated that localization on both the plasma membrane and amyloplasts is necessary for gravity signaling in roots, indicating its fundamental role in this process," added Hiromasa Shikata, Assistant Professor at NIBB and the co-first author.
"Professor Miyo Terao Morita further emphasized, "LZYs act as signal molecules, transmitting positional information from amyloplasts to the plasma membrane, where the regulation of auxin transport occurs." This revelation provides compelling support for the "position sensor hypothesis," explaining gravity sensing in plants through the proximity or the contact between statoliths and the plasma membrane."
Comment: another complex mechanism that cannot have been discovered by chance. Upright plants had to have this mechanism at the beginning of their existence.
Biochemical controls: cell division atomic level
by David Turell , Monday, August 14, 2023, 17:40 (51 days ago) @ David Turell
Latest technique:
https://www.sciencealert.com/we-just-got-an-unprecedented-look-at-the-details-of-cell-d...
"The innovative tweak will allow scientists to directly observe molecular behavior over a much longer period, opening a window onto pivotal biological processes like cell division.
"'The living cell is a busy place with proteins bustling here and there," explains University of Michigan biomedical engineer Guangjie Cui. "Our superresolution is very attractive for viewing these dynamic activities." (my bold)
"Superresolution is a process for observing incredibly small biological structures. It uses a series of snapshots taken of constellations of fluorescing molecules that highlight select areas of the targeted tissue, eliminating the blurring effect of a flood of diffracted light.
***
"The resulting system allows a staggering 250 hours of continued observations at a resolution of just 100 atoms.
"Cui and colleagues then examined the entire process of cellular division with their new PINE nanoscopy, revealing a never-before-seen behavior of actin molecules, down to the individual molecule level.
"Actin, the major component of a cell's cytoskeleton, provides cells with structural support and helps facilitate movement within a cell. So these branching filament shaped molecules play a massive role in dividing a cell before pulling it apart into two daughter cells.
***
"Observing 904 actin filaments during the cell division process, Cui and his team could see how individual molecules behaved with each other. They found that when actin molecules are less bound to one another they will expand in search of more links. As each actin reaches its neighbors, it draws other actin molecules close, increasing its network further.
"The researchers saw how these small scale movements translated across a larger scale cellular view. Unexpectedly, when actin expands the cell at large actually contracts, whereas it expands when actin contracts. This seems contradictory so the researchers are keen to explore how this opposing motion is occurring."
Comment: the Actin molecules act as if they had minds of their own, but something must control them but yet discovered. (note my bold) This complexity demonstrates it must have been designed.
Biochemical controls: nucleolus formation
by David Turell , Tuesday, August 15, 2023, 17:10 (50 days ago) @ David Turell
Controlled in part by one molecule:
https://phys.org/news/2023-08-nucleolus-evolved.html
"MIT biologists have now discovered that a single scaffolding protein is responsible for the formation of one of these condensates, which forms within a cell organelle called the nucleolus. Without this protein, known as TCOF1, this condensate cannot form.
"The findings could help to explain a major evolutionary shift, which took place around 300 million years ago, in how the nucleolus is organized. Until that point, the nucleolus, whose role is to help build ribosomes, was divided into two compartments. However, in amniotes (which include reptiles, birds, and mammals), the nucleolus developed a condensate that acts as a third compartment. Biologists do not yet fully understand why this shift happened.
***
"Now that the researchers know how this condensate, known as the fibrillar center, forms, they may be able to more easily study its function in cells. The findings also offer insight into how other condensates may have originally evolved in cells, the researchers say.
***
"'Almost every cellular process that is essential for the functioning of the cell has been associated somehow with condensate formation and activity," Calo says. "However, it's not very well sorted out how these condensates form."
"In a 2022 study, Calo and his colleagues identified a protein region that seemed to be involved in forming condensates. In that study, the researchers used computational methods to identify and compare stretches of proteins known as low-complexity regions (LCRs), from many different species. LCRs are sequences of a single amino acid repeated many times, with a few other amino acids sprinkled in.
"That work also revealed that a nucleolar protein known as TCOF1 contains many glutamate-rich LCRs that can help scaffold biomolecular assemblies.
"In the new study, the researchers found that whenever TCOF1 is expressed in cells, condensates form. These condensates always include proteins usually found within a particular condensate known as the fibrillar center (FC) of the nucleolus. The FC is known to be involved in the production of ribosomal RNA, a key component of ribosomes, the cell complex responsible for building all cellular proteins.
"However, despite its importance in assembling ribosomes, the fibrillar center appeared only around 300 million years ago; single-celled organisms, invertebrates, and the earliest vertebrates (fish) do not have it.
The new study suggests that TCOF1 was essential for this transition from a "bipartite" to "tripartite" nucleolus.
***
"The researchers also found that the essential region of TCOF1 that helps it form scaffolds is the glutamate-rich low-complexity regions. These LCRs appear to interact with other glutamate-rich regions of neighboring TCOF1 molecules, helping the proteins assemble into a scaffold that can then attract other proteins and biomolecules that help form the fibrillar center.
"'What's really exciting about this work is that it gives us a molecular handle to control a condensate, introduce it into a species that doesn't have it, and also get rid of it in a species that does have it. That could really help us unlock the structure-to-function relationship and figure out what is the role of the third compartment," Jaberi-Lashkari says.
"Based on the findings of this study, the researchers hypothesize that cellular condensates that emerged earlier in evolutionary history may have originally been scaffolded by a single protein, as TCOF1 scaffolds the fibrillar center, but gradually evolved to become more complex.
"'Our hypothesis, which is supported by the data in the paper, is that these condensates might originate from one scaffold protein that behaves as a single component, and over time, they become multicomponent," Calo says."
Comment: bit by bit the entire complexity of the single cell is being unraveled. Designs like this are not results of chance mutations.
Biochemical controls: molecular language
by David Turell , Thursday, August 17, 2023, 17:19 (48 days ago) @ David Turell
How molecules talk/communicate with each other:
https://www.sciencedaily.com/releases/2023/08/230815151131.htm
"Two molecular languages at the origin of life have been successfully recreated and mathematically validated, thanks to pioneering work by Canadian scientists at Université de Montréal.
***
"Living organisms are made up of billions of nanomachines and nanostructures that communicate to create higher-order entities able to do many essential things, such as moving, thinking, surviving and reproducing.
"'The key to life's emergence relies on the development of molecular languages -- also called signalling mechanisms -- which ensure that all molecules in living organisms are working together to achieve specific tasks," said the study's principal investigator, UdeM bioengineering professor Alexis Vallée-Bélisle.
***
"One well-known molecular language is allostery. The mechanism of this language is "lock-and-key": a molecule binds and modifies the structure of another molecule, directing it to trigger or inhibit an activity.
'Another, lesser-known molecular language is multivalency, also known as the chelate effect. It works like a puzzle: as one molecule binds to another, it facilitates (or not) the binding of a third molecule by simply increasing its binding interface.
"Although these two languages are observed in all molecular systems of all living organisms, it is only recently that scientists have started to understand their rules and principles -- and so use these languages to design and program novel artificial nanotechnologies.
"'Given the complexity of natural nanosystems, before now nobody was able to compare the basic rules, advantage or limitations of these two languages on the same system," said Vallée-Bélisle.
"To do so, his doctoral student Dominic Lauzon, first author of the study, had the idea of creating a DNA-based molecular system that could function using both languages. "DNA is like Lego bricks for nanoengineers," said Lauzon. "It's a remarkable molecule that offers simple, programmable and easy-to-use chemistry."
***
"For example, while the multivalent language enabled control of both the sensitivity and cooperativity of the activation or deactivation of the molecules, the corresponding allosteric translation only enabled control of the sensitivity of the response.
"With this new understanding at hand, the researchers used the language of multivalency to design and engineer a programmable antibody sensor that allows the detection of antibodies over different ranges of concentration.
"'As shown with the recent pandemic, our ability to precisely monitor the concentration of antibodies in the general population is a powerful tool to determine the people's individual and collective immunity," said Vallée-Bélisle.
"In addition to expanding the synthetic toolbox to create the next generation of nanotechnology, the scientist's discovery also shines a light on why some natural nanosystems may have selected one language over another to communicate chemical information."
Comment: I presented this to make point that organic chemistry is highly complex in how molecules interact. Inorganic chemistry is simple. Sodium and chlorine simply quickly join into water. Assuming God started life, organic chemistry is an unnatural development, and we are slowly unraveling its mysteries. It requires enzymes, huge molecules, to make things happen. Alone they are quite an invention. So is all the rest.
Biochemical controls: gut stem cell development
by David Turell , Saturday, August 19, 2023, 16:15 (46 days ago) @ David Turell
Type established first then migration:
https://phys.org/news/2023-08-stem-cells-identity.html
"These discoveries were made using intestinal organoids and the new TypeTracker technique, which can now be used to understand other organs at the cellular level and the effects of mutations and medications.
***
"Our intestines contain different types of cells, each of which has a specific task. Just like in many other places in our body, the cells in the intestines are constantly renewed: stem cells develop into specialized cells that perform a function, for example, to secrete substances that protect the intestine or to absorb nutrients from food.
"'From previous research we know that stem cells reside in the valleys of the intestinal wall (the 'crypts'), while most specialized and functional cells are located at the top of the mountains (the 'villi')," say Sander Tans and Jeroen van Zon, who directed the research jointly at AMOLF.
"'The cells in the intestinal wall are renewed about every week, using the stem cells in the crypts that grow, divide and migrate to the villi. We used to think that by moving upwards to the villus, the stem cells are instructed to become a functional cell. This has been a very appealing model, as it naturally explains how these functional cells are positioned at the right location. However, our data shows a different picture."
***
"This new type of data showed that stem cells adopted their functional identity much earlier than previously thought. They did so when still deep inside the crypt, before migrating towards the villus region that was thought to provide the trigger to start the specialization process.
***
"'Various medical conditions are thought to be caused by an imbalance between cell types. For instance those that secrete hormones, which has been linked to intestinal bowel syndrome (IBS), the sensation of fullness, but also the so-called gut-brain axis.
"'Understanding how cells choose their identity is key to uncovering the regulation of this balance, and to controlling it through medical interventions. Furthermore, if we want to better understand which molecular signals underpin the fate choices, we need to look into the earlier stages, when cells still have a strong stem identity and other known molecular signals, such as the WNT pathway that plays a role in cell specialization, are still high."
"The equipment and procedure for the TypeTracker method is relatively simple. Therefore, it is also promising for all types of other research on organoids. "Cell identity is central to all organ functions, and was previously only known in static pictures. This method allows one to look at the dynamics at the cellular level. One can for instance investigate whether the same commit-then-sort principle holds for other organs with a completely different three-dimensional structure, such as breast tissue that consists of channels," says Zheng."
comment: I wonder if this principal applies to all aspects of stem cells in embryology.
Biochemical controls: building cilia
by David Turell , Friday, August 25, 2023, 20:33 (40 days ago) @ David Turell
Important in many organs:
https://phys.org/news/2023-08-secrets-cilia-nsl-complex-intraciliary.html
"Cilia are thin, eyelash-like extensions on the surface of cells. They perform a wide variety of functions, acting as mechanosensors or chemosensors, and play a crucial role in many signaling pathways.
***
"The proper assembly, maintenance, and function of cilia rely on a process called "intraciliary transport." Components of the intraciliary transport system "walk" on the microtubule to deliver cargo between the cell body and the ciliary tip to ensure a constant supply of materials.
***
"The NSL complex is a potent epigenetic modifier that regulates thousands of genes in fruit flies, mice, and humans. However, most of the functions of the NSL complex remain mysterious and have only recently begun to be elucidated. "Previous research from our lab indicates that the NSL complex controls many pathways critical for organismal development and cellular homeostasis," says Akhtar, Director at the MPI of Immunobiology and Epigenetics in Freiburg.
"The complex comprises several proteins and is a histone acetyltransferase (HAT) complex that prepares the genes for activation. "Think of gene regulation as a team effort with different players. One important player is the NSL complex. It puts special marks on the histone proteins on which the DNA is wrapped around in the nucleus, like putting up green flags. These flags tell other regulators to switch on specific genes. We now found that the NSL complex does exactly this for a group of genes linked to moving materials within cilia," says Tsz Hong Tsang, the first author of the study.
"'The intraciliary transport system is essential because it is needed to build a functional cilium. The cell uses the intraciliary transport system to move material from the cilium base to the growing tip—similar to building a tower. In the study, the researchers used mouse cells to determine the functional consequences of the loss of the NSL complex in the cells.
They found that fibroblast cells lacking the NSL complex protein KANSL2 could not activate the transport genes nor assemble cilia. "As cilia are the sensory and signaling hubs for cells, loss of KANSL2 leads to the inability of cells to activate the sonic hedgehog signaling pathway, which plays important roles in the regulation of embryonic development, cell differentiation, and maintenance of adult tissues as well as cancer," says Akhtar.
"Although tiny protrusions, these sensory organelles are incredibly important to cells. Ciliopathies, which affect organs as diverse as the kidney, liver, eye, ear, and central nervous system, remain challenging for biological and clinical studies. The researchers at the Max Planck Institute in Freiburg hope that their analysis of the role of the NSL complex has provided important insights into the regulation of these organelles and the genes associated with them, thus contributing to human health."
Comment: cilia are vital components of many organs. their construction process is irreducibly complex and must be designed all at once. Teh NSL complex is also irreducibly complex and must be designed all at once:
https://www.science.org/doi/10.1126/sciadv.adh5598
Not by chance.
Biochemical controls: cell control of mRNA
by David Turell , Friday, August 25, 2023, 20:42 (40 days ago) @ David Turell
More intracellular complexity:
https://phys.org/news/2023-08-modification-mrna-cellular-protein-synthesis.html
"RNA has a central role in the cell's protein production. New research shows that RNA can be changed through various chemical modifications, the function of which is unknown to most.
***
"'Our findings show that already from the production of an mRNA (during transcription), the cell can put on chemical modifications that can control how that mRNA is translated into protein," says Chiara Pederiva, postdoc at the Department of Cell and Molecular Biology, Karolinska Institutet and the study's first author.
"'Our findings reveal that an RNA modification called pseudouridylation controls how quickly mRNA is translated into protein. We show which enzyme performs this modification (dyskerin), when it occurs in the cell (already during transcription) and what happens if this modification does not occur (abnormal protein production).
***
"This provides important information about one of the cell's most central processes—protein production—and how the cell can control protein production in the cytoplasm right from the transcription of mRNA, which takes place in the cell nucleus.
***
"The importance of RNA modifications for cellular processes and disease development is a research field in its infancy. These new findings raise the knowledge to a new level and can help in the development of new therapies."
Comment: we still do not know the full extent of intracellular complexity which must be seen as requiring design.
Biochemical controls: treadmilling for cell division
by David Turell , Friday, August 25, 2023, 20:54 (40 days ago) @ David Turell
New finding:
https://www.sciencedaily.com/releases/2023/08/230824111805.htm
"Researchers at the Centre for Genomic Regulation (CRG) have discovered how proteins work in tandem to regulate 'treadmilling', a mechanism used by the network of microtubules inside cells to ensure proper cell division.
***
"Microtubules are long tubes made of proteins that serve as infrastructure to connect different regions inside of a cell. Microtubules are also critical for cell division, where they are key components of the spindle, the structure which attaches itself to chromosomes and pulls them apart into each new cell.
"For the spindle to function properly, cells rely on microtubules to 'treadmill'. This involves one end of the microtubule (known as the minus end) to lose components while the other (the plus end) adds components. The effect is like that of a treadmill conveyor belt, where the microtubules appear to be moving continuously without changing their overall length.
***
"Despite the central role of treadmilling in cell biology, how the process is regulated has remained a mystery -- till now. The authors of the study used various isolated proteins known to play a central role in microtubule biology, putting them together in a test tube and visualizing them using a microscope.
"Three proteins were found to be critical for regulating treadmilling: KIF2A, a protein belonging to a larger family of proteins that dismantles microtubules, the γ-tubulin ring complex (γ-TuRC), a scaffold for microtubules to grow from, and spastin, an enzyme that acts like a scissor cutting microtubules.
"'The family of proteins that dismantle microtubules usually nibble on microtubules at both ends. We were surprised to find that one member of this family -- KIF2A -- has a strong preference for minus ends. This specialization is exactly what researchers have been looking for to explain why microtubules treadmill in the spindle," explains Dr. Thomas Surrey, senior author of the study and researcher at the Centre for Genomic Regulation.
"Before KIF2A can nibble a minus end, it needs to overcome yTuRC, which acts like a safety cap. "The enzyme spastin is required to free microtubules from the safety cap so that KIF2A can do its job once microtubule plus ends have grown long enough," explains Dr. Cláudia Brito, co-first author of the study. The researchers found that the correct control of treadmilling requires the coordinated action of all three proteins. While the study does not directly translate into therapeutic avenues, it adds another piece to the intricate puzzle of cellular function and division. "Humans start as a single cell which must develop into many trillions of cells, all containing good copies of the genome. It's amazing and important that this process works extremely reliably, so we have added a small piece of the puzzle in understanding the overall mechanism," concludes Dr. Henkin." (my bold)
Comment: My bolded statement above is not hyperbole but obviously a vital point. Very tight feedback controls must be in place. Again, an example of irreducible complexity.
Biochemical controls: garbage disposal
by David Turell , Saturday, August 26, 2023, 20:33 (39 days ago) @ David Turell
Getting rid of old proteins:
https://www.sciencedaily.com/releases/2023/08/230824150719.htm
"Short-lived proteins control gene expression in cells to carry out a number of vital tasks, from helping the brain form connections to helping the body mount an immune defense. These proteins are made in the nucleus and are quickly destroyed once they've done their job.
***
"...the researchers homed in on midnolin as a protein that helps break down both transcription factors. Follow-up experiments revealed that in addition to Fos and EGR1, midnolin may also be involved in breaking down hundreds of other transcription factors in the nucleus.
***
"They established that midnolin has a "Catch domain" -- a region of the protein that grabs other proteins and feeds them directly into the proteasome, where they are broken down. This Catch domain is composed of two separate regions linked by amino acids (think mittens on a string) that grab a relatively unstructured region of a protein, thus allowing midnolin to capture many different types of proteins. (my bold)
"Of note are proteins like Fos that are responsible for turning on genes that prompt neurons in the brain to wire and rewire themselves in response to stimuli. Other proteins like IRF4 activate genes that support the immune system by ensuring that cells can make functional B and T cells.
"'The most exciting aspect of this study is that we now understand a new general, ubiquitination-independent mechanism that degrades proteins," Elledge said.
"In the short term, the researchers want to delve deeper into the mechanism they discovered. They are planning structural studies to better understand the fine-scale details of how midnolin captures and degrades proteins. They are also making mice that lack midnolin to understand the protein's role in different cells and stages of development.
"The scientists say their finding has tantalizing translational potential. It may offer a pathway that researchers can harness to control levels of transcription factors, thus modulating gene expression, and in turn, associated processes in the body.
"'Protein degradation is a critical process and its deregulation underlies many disorders and diseases," including certain neurological and psychiatric conditions, as well as some cancers, Greenberg said."
Comment: These short-lived proteins know what to grab. We do not know how they know what to do. Designed automatic ionic attraction is one way, but another is the 'Catch domain' which acts as a lock and key connection. All automatic.
Biochemical controls: cells form cilia
by David Turell , Sunday, August 27, 2023, 18:00 (38 days ago) @ David Turell
To communicate and for other functions:
https://www.sciencedaily.com/releases/2023/08/230825140357.htm
"The NSL (non-specific lethal) complex regulates thousands of genes in fruit flies and mammals. Silencing the NSL genes leads to the death of the organism, which gave the complex its curious name. Researchers have now discovered that the genes regulated by the NSL complex also include genes of the intraciliary transport system. This enables different cell types to form cilia on their surface, which are important for cell communication. The study shows that these genes are 'switched on' by the NSL complex, regardless of whether a particular cell has cilia or not. The researchers found that this class of cilia-associated genes is crucial for the function of podocytes. This is a highly specialized cell type of the kidney that, paradoxically, does not have cilia. These findings have important implications for ciliopathies and kidney disease.
***
"The proper assembly, maintenance, and function of cilia rely on a process called "intraciliary transport." Components of the intraciliary transport system "walk" on the microtubule to deliver cargo between the cell body and the ciliary tip to ensure a constant supply of materials...In their recent study in the journal Science Advances, the lab of Asifa Akhtar identified the NSL complex as a transcriptional regulator of genes known for their roles in the intraciliary transport system of cilia across multiple cell types.
***
"The complex comprises several proteins and is a histone acetyltransferase (HAT) complex that prepares the genes for activation. "Think of gene regulation as a team effort with different players. One important player is the NSL complex. It puts special marks on the histone proteins on which the DNA is wrapped around in the nucleus, like putting up green flags. These flags tell other regulators to switch on specific genes. We now found that the NSL complex does exactly this for a group of genes linked to moving materials within cilia," says Tsz Hong Tsang, the first author of the study.
***
"The intraciliary transport system is essential because it is needed to build a functional cilium. The cell uses the intraciliary transport system to move material from the cilium base to the growing tip -- similar to building a tower.
***
"They found that fibroblast cells lacking the NSL complex protein KANSL2 could not activate the transport genes nor assemble cilia. "As cilia are the sensory and signaling hubs for cells, loss of KANSL2 leads to the inability of cells to activate the sonic hedgehog signaling pathway, which plays important roles in the regulation of embryonic development, cell differentiation, and maintenance of adult tissues as well as cancer," says Asifa Akhtar."
Comment: my usual view is that this degree of complexity requires a designing mind.
Biochemical controls: intercellular transport
by David Turell , Friday, September 01, 2023, 20:50 (33 days ago) @ David Turell
Now described as Maxwell's demon:
https://www.sciencealert.com/hypothesized-physics-demon-may-have-been-found-lurking-ins...
"Back in 1867, in an effort to test his thoughts on the emerging science of thermodynamics, physicist James Clerk Maxwell imagined an intelligent 'demon' sorting molecules between two containers based on their energy.
"In 2023, a less diabolical version of Maxwell's fictitious demon may have been found.
"According to a new study from researchers at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, proteins embedded in cell membranes called ATP-Binding Cassette (ABC) transporters have features that echo Maxwell's demon, allowing them to sort substrates.
"In fact, these ABC transporters have been around for billions of years and can be found in almost every living organism. What's more, they fit within natural thermodynamic laws.
"It turns out that Maxwell was unknowingly describing a fundamental aspect of life's very building blocks. (my bold)
***
"As a part of the system (and, magical little devil, unreliant on energy himself), the demon would create energy from the resulting temperature difference from absolutely nothing.
***
"Scientists have previously suspected something like Maxwell's demons might be involved with the energy intensive process of transporting molecules against their natural concentration gradient flow. But this is the first time the information framework of such a system has been described and modeled in a way that harkens back to Maxwell's famous thought experiment.
"What the researchers propose is that the ABC transporters on cell membranes control molecule flow in the same way as Maxwell demons, using energy from ATP (adenosine triphosphate) molecules to power the process. (my bold)
"The biochemical structure of the transporters then do the measuring, feedback and resetting, depending on the position of the molecule being transported as seen in the diagram above.
"It's an important discovery, because it teaches us more about how cells are able to regulate their environments and function as they need to, by managing molecule import and export, much like a tiny demon at a cell's door.
"While the researchers did make some simplifications in order for their calculations to work, they're confident that what they've outlined in their study paper can be applied to more complex systems – systems which are widespread in nature."
Comment: a beautiful automatic system for intracellular communication.
Biochemical controls: intracellular garbage removal
by David Turell , Wednesday, September 27, 2023, 18:28 (7 days ago) @ David Turell
Cell organelles known as 'peroxisomes' dispose toxic substances and fats:
https://www.sciencedaily.com/releases/2023/09/230927003432.htm
"'We can imagine peroxisomes being like miniature factories which specialise in different tasks," Gatsogiannis explains. "First of all, they are known for 'detoxifying' the cell. They act as cellular waste disposal units in our cells." This waste can be excess fatty acids, for example, or toxic substances from the environment: at least 50 different processes of this kind are attended to by cell organelles only 0.5 micrometres in size (1 micrometre = 1 millionth of a millimetre).
"Something that is particularly important for the system is the role played by peroxisomes in fat metabolism. This is because they not only dismantle the fats, they also convert them into usable energy which itself is indispensable for a variety of processes in the body. Without peroxisomes, dangerous quantities of certain fats can accumulate, which would give rise to serious health problems.
***
"Each of these processes requires a series of specific enzymes. The peroxisomes, however, are surrounded by a biological membrane which the proteins cannot readily permeate, which means that they have to be imported. This importing mechanism needs energy and a further group of proteins -- the Pex group. "Just like a truck, which transports products from one place to another, the transportation of enzymes requires a transportation protein, energy and well-thought out logistics in order to work efficiently," is the comparison drawn by PhD student Maximilian Rüttermann, a member of the team. "And, again just like a truck, the protein is used again or recycled until ultimately it falls apart or disintegrates."
"This recycling mechanism is the only energy-intensive step in the entire importing process. The main role is played by the perixisomal AAA-ATPase complex Pex1/Pex6: this "biological nanomachine" unpacks and unfolds the spent proteins so that they can be recycled or disposed of. AAA-ATPases are basically a kind of cellular cleaning crew which keeps the inner surroundings of the cell clean, functional and ready for the demands of life.
***
"The high-resolution structures show how the Pex1 and Pex6 proteins work together synchronically. They pull out of the membrane a substrate similar to the import receptors used in order to enable them to be recycled -- a unique mechanism, comparable to a row of arms which, step by step, pull a thick rope in pairs and, in the process, untie its knots. "The atomic structures and an understanding of the mechanism of this complex nanomachine now enable us to understand important steps in peroxisome physiology in health and disease," says Gatsogiannis in conclusion."
Comment: this is a vital irreducibly complex mechanism without which cells would die. From teh article: "most of the malfunctions in peroxisomal biogenesis are associated with mutations in Pex1 or Pex6, with up to 60 percent of all cases being attributable to a rare genetic disorder in which the patient's cells are not able to form peroxisomes. This is something which the general public is not aware of, as patients affected die as a rule just a few days or weeks after their birth -- and there is no known cure as yet." Only a designer could create this necessary mechanism.
Biochemical controls: appetite controls
by David Turell , Monday, October 02, 2023, 18:15 (2 days ago) @ David Turell
In very early evolution:
https://www.the-scientist.com/ts-digest/issue/designer-peptoids-pop-viral-membranes-20-...
"A neuropeptide suppressed feeding in two evolutionarily distant species, suggesting that hunger regulation may go back to the roots of the tree of life.
"Neuropeptides, small proteins released by the nervous system, regulate how much food animals eat. To find out how long these molecules have been playing this role, Vladimiros Thoma, an assistant professor at Tohoku University, turned his attention to jellyfish. “Jellyfish and also other animals called comb jellies are studied as candidates for the origins of neurons,” Thoma explained, making them perfect models for investigating that question.
"Using the jellyfish Cladonema pacificum, Thoma and his colleagues discovered a peptide that controls feeding both in jellyfish and fruit flies, animals that shared a common ancestor millions of years ago. Their findings suggest deep evolution roots for the role of neuropeptides in appetite regulation.
"The team starved jellyfish for about 50 hours and compared the gene expression profiles of starved and recently fed jellyfish. They found that feeding changed the expression of several genes, including those encoding neuropeptides. After screening the ability of these molecules to control food intake, they found five feeding suppressors, among which was the peptide GLWamide.
“'These Wamide peptides were originally discovered in insects,” said Meet Zandawala, a neuropeptide researcher at the University of Nevada, Reno, who was not involved in the study. “It is quite interesting to find these peptides in such [simple] animals.”
"The team also showed that GLWamide is expressed in neurons in jellyfish tentacles, and that it inhibited the tentacle contraction movement to suppress feeding.
"Next, the researchers tested whether GLWamide worked similar to myoinhibitory peptide (MIP), a known appetite regulator in fruit flies. They bathed jellyfish with MIP and generated transgenic flies that expressed GLWamide but lacked MIP. They found that MIP reduced the jellyfish’s shrimp intake, while GLWamide decreased the number of times flies stuck out their proboscises to ingest a drop of sugary water.
“'This signal is evolutionarily conserved. It is also in the flies, and it seems to work the same way,” Thoma explained. “It is kind of striking that over millions of years, you still have a very similar system.'”
Comment: more evidence of convergence. The issue raised is simple: in a chance discovery system like Darwin's theory of evolution why should the same chemicals appear in basically unrelated species? A designer would logically use the same set of chemicals over and over. Convergence argues for design.
Biochemical controls: strange strings on proteins function
by David Turell , Monday, October 02, 2023, 23:08 (2 days ago) @ David Turell
They are called intrinsically disordered regions (IDRs):
https://phys.org/news/2023-10-reveals-overlooked-proteins-critical-fundamental.html
"Around half of all proteins have stringy, unstructured bits hanging off them, dubbed intrinsically disordered regions, or IDRs. Because IDRs have more dynamic, "shape-shifting" geometries, biologists have generally thought that they cannot have as precise of a fit with other biomolecules as their folded counterparts, and as such, assumed these thread-like entities may contribute less significantly to overall protein function.
"Now, a multi-institutional collaboration has uncovered how a key aspect of cell biology is controlled by IDRs. Their study, published in the journal Cell, reveals that IDRs have specific and important interactions that play a central role in chromatin regulation and gene expression, essential processes across every living cell.
"The researchers focused on disordered regions of the human cBAF complex, a multi-component group of proteins in the nucleus that works to open up the densely coiled-up DNA inside cells called chromatin, enabling genes along DNA to be expressed and turned into proteins. Mutations in the IDRs of one family of cBAF subunits, ARID1A and ARID1B, which are highly frequent in cancer and neurodevelopmental disorders, throw chromatin remodeling and gene expression out of whack, suggesting IDRs are anything but trivial extras. (my bold)
"In particular, the study revealed that the IDRs form little droplets called condensates that separate out from surrounding cellular fluid, just like drops of oil in water. The specific interactions that happen in these condensates allow proteins and other biomolecules to congregate in particular locations to carry out cellular activities. While scientists have shown that condensates perform a myriad of tasks, it was not known if these special liquid droplets had any role in chromatin remodeling, nor whether their specific amino acid sequences served specific functions.
"Researchers from Princeton, the Dana-Farber Cancer Institute and Washington University in St. Louis teamed up to study the effects of different mutations in the ARID1A/B IDRs on the ability of the cBAF protein complex to form condensates and recruit partner proteins needed for gene expression.
***
"'For the first time, we've shown that intrinsically disordered regions are fundamentally important for operation of a key chromatin remodeling complex, the cBAF complex" said Amy Strom, co-lead author of the study. "Our findings should be applicable to IDRs in general and could have significant implications for how cells do everything they do."
***
"Brangwynne, whose lab has studied disordered sequences and their role in forming condensates for years, said "Intrinsically disordered regions are everywhere in the vast catalog of human and other organisms' proteins, and they're playing central roles in physiology and disease in ways we're just starting to understand.'"
Comment: an important new finding telling us that all proteins, like all DNA are there for a purpose. Human invented 'junk DNA' and now it is gone. Ignoring IDR's (note my bold) is simply humans thinking they are smarter than the designer.
Biochemical controls: intracellular quantum actions
by David Turell , Saturday, September 09, 2023, 21:25 (25 days ago) @ David Turell
Molecules have quantum reactions:
https://www.newscientist.com/article/2390076-why-nature-is-the-ultimate-quantum-engineer/
"I started haphazardly reading about a protein that senses magnetic fields in a way I thought was only possible with high-tech quantum experiments. But there was no doubt: This was bona fide “quantum sensing”.
***
"In biology, researchers historically took for granted that quantum effects must disappear, washed out in what Erwin Schrödinger called the “warm, wet environment of the cell”. Most scientists still believe biology can be adequately described by classical physics: No funky barrier crossings, no being in multiple locations simultaneously. (my bold)
"However, there is increasing evidence that biology uses quantum properties to function and optimally respond to external stimuli, as is the case with the protein that senses magnetic fields.
"The protein in question, like many, many others, senses magnetic fields because of something called a spin-dependent chemical reaction, involving both my favourite quantum object – the electron – and my favourite quantum property – spin.
***
"Spin is distinctly quantum in nature, with particular magnetic fields being able to put a particle’s spin in a quantum state that encompasses both up and down simultaneously. This phenomenon is known as superposition.
"Some chemical reactions are influenced by the superposition states of specific electron spins. Since magnetic fields can affect these states, they can also impact the macroscopic outcomes of these reactions. And this is exactly how the protein works: It interacts with, or “senses”, very tiny magnetic fields using electron spin as a quantum detector. And it can do this all at room temperature, in a messy solution with millions of molecules; in other words, within an environment where quantumness is not expected to survive for long, let alone to be used as a resource.
***
"Still, even though there is not yet a smoking gun proving that cells work this way, there is correlative evidence that electron spin-dependent chemical reactions do alter the function of living cells. Birds can sense Earth’s tiny magnetic field as a migratory cue. They seem to do so via a magnetosensitive protein called a cryptochrome – the very same protein that caught my attention all those years ago.
"There is also evidence that weak magnetic fields lead to physiological responses across the tree of life, in vertebrates, invertebrates, plants and bacteria. These effects range from changes in DNA repair rates and the production of cellular oxidants to neurological function and cell metabolism, to name a few. So much of the machinery of how cells work appears to be tweakable by weak magnetic fields in a quantum manner.
***
"What is currently missing is a comprehensive understanding of exactly how different electron spin superposition states correspond to different physiological outcomes within a cell or tissue. But if we develop a quantum biology “codebook”, it could give us deterministic control over many of our physiological responses.
"In my lab, we are working on this codebook. We hope that it will eventually lead to simple electronic devices that could produce electromagnetic interventions for disease prevention and more.
"Humankind is only at the start of its journey to understand quantum mechanics. Over billions of years, nature has already become the ultimate quantum engineer."
Comment: the key to her article is that it tells us protein folding and reactions are accomplished by guidance from electromagnetic field influences. Biochemicals in cell fluids are not really free-floating but tightly controlled by these influences. And all of this is under direct genetic control monitoring automatic activity.
Biochemical controls: how RNA is supplied and delivered
by David Turell , Monday, March 06, 2023, 19:09 (212 days ago) @ David Turell
Like American mail ZIP codes, there is a very definite system:
https://phys.org/news/2023-03-rna-city-cell-cellular-codes.html
"RNA is a chemical cousin of DNA. It plays many roles in the cell, but perhaps it's most well-known as the relay messenger of genetic information. RNA takes a copy of the information in DNA from its storehouse in the nucleus to sites in the cell where this information is decoded to create the building blocks—proteins—that make cells what they are. This transport process is critical for animal development, and its dysfunction is linked to a variety of genetic diseases in people.
"In some ways, cells are like cities, with proteins carrying out specific functions in the "districts" they occupy. Having the right components at the right time and place is essential.
***
"The instructions for making a given protein are contained within RNA. One way to ensure proteins are where they are supposed to be is to transport their RNA blueprint to where their specific functions are needed. But how does RNA get where it needs to be?
***
"For a handful of mRNAs—or RNA sequences coding for specific proteins—researchers have an idea about how they're transported. They often contain a particular string of nucleotides, the chemical building blocks that make up RNA, that tell cells about their desired destination. These sequences of nucleotides, or what scientists refer to as RNA "ZIP codes," are recognized by proteins that act like mail carriers and deliver the RNAs to where they are supposed to go.
***
"We found that one protein that regulates neurite production, named Unkempt, repeatedly appeared with ZIP code-containing RNAs. When we depleted cells of Unkempt, the ZIP codes were no longer able to direct RNA transport to neurites, implicating Unkempt as the "mail carrier" that delivered these RNAs.
"With this work, we identified ZIP codes that sent RNAs to neurites (in our analogy, the bank). But where would an RNA containing one of these ZIP codes end up if it were in a cell that didn't have neurites (a city that didn't have a bank)?
"To answer this, we looked at where RNAs were in a completely different cell type, epithelial cells that line the body's organs. Interestingly, the same ZIP codes that sent RNAs to neurites sent them to the bottom of epithelial cells. This time we identified another mail carrier, a protein called LARP1, responsible for the transport of RNAs containing a particular ZIP code to both neurites and the bottom end of epithelial cells.
"How could one ZIP code and mail carrier transport an RNA to two different locations in two very different cells? It turns out that both of these cell types contain structures called microtubules that are oriented in a very particular way. Microtubules can be thought of as cellular streets that serve as tracks to transport a variety of cargo in the cell. Importantly, these microtubules are polarized, meaning they have ingrained "plus" and "minus" ends. Cargo can therefore be transported in specific directions by targeting to one of these ends.
***
"We could compare this process to a mailing address. While the top line ("The Bank") tells us the name of the building, it's really the address and street name ("150 Maple Street") that contains actionable information for the mail carrier. These RNA ZIP codes send RNAs to specific places along microtubule streets, not to specific structures in the cell. This allows for a more flexible yet uniform code, as not all cells share the same structures."
Comment: the bits and pieces of this complex system cannot be evolved bit by bit. It must be designed to all be together from the beginning.
Biochemical controls: sight from initial molecule's actions
by David Turell , Wednesday, March 22, 2023, 20:26 (196 days ago) @ David Turell
Very first biochemistry for sight:
https://phys.org/news/2023-03-molecular-eye-retina.html
"It only involves a microscopic change of a protein in our retina, and this change occurs within an incredibly small time frame: it is the very first step in our light perception and ability to see. It is also the only light-dependent step. PSI researchers have established exactly what happens after the first trillionth of a second in the process of visual perception, with the help of the SwissFEL X-ray free-electron laser of the PSI.
"At the heart of the action is our light receptor, the protein rhodopsin. In the human eye it is produced by sensory cells, the rod cells, which specialize in the perception of light. Fixed in the middle of the rhodopsin is a small kinked molecule: retinal, a derivative of vitamin A. When light hits the protein, retinal absorbs part of the energy. With lightning speed, it then changes its three-dimensional form so the switch in the eye is changed from "off" to "on." This triggers a cascade of reactions whose overall effect is the perception of a flash of light.
***
"During this "breathing in" stage, the protein temporarily loses most of its contact with the retinal that sits in its middle. "Although the retinal is still connected to the protein at its ends through chemical bonds, it now has room to rotate." At that moment, the molecule resembles a dog on a loose leash that is free to give a jerk.
"Shortly afterwards the protein contracts again and has the retinal firmly back in its grasp, except now in a different more elongated form. "In this way the retinal manages to turn itself, unimpaired by the protein in which it is held."
"The transformation of the retinal from 11-cis kinked form into the all-trans elongated form only takes a picosecond, or one trillionth (10-12) of a second, making it one of the fastest processes in all of nature."
Comment: what taught the molecule to react that way? Darwinian trial and error? Laughable. Only design fits.
Biochemical controls: specialized retinal synapses
by David Turell , Monday, June 19, 2023, 15:56 (107 days ago) @ David Turell
In specialized retinal cells:
https://medicalxpress.com/news/2023-06-uncovers-synaptic-intricacies-retina.html
"Cone synapses inside the eye's retina help the brain process changes in light. It's a unique synapse because it is has evolved to signal changes in light intensity, said Steven DeVries, MD, Ph.D., the David Shoch, MD, Ph.D., Professor of Ophthalmology.
"'Counterintuitively, cone neurotransmitter release is high in the dark and reduced by light. When the light's brighter, the reduction is larger. When the lights are dimmer, it's smaller; it operates differently from most synapses which use an increase in transmitter release to signal all-or-nothing, digital action potentials," DeVries said.
"Unlike most other synapses in the brain, each individual cone synapse is connected to more than a dozen different types of post-synaptic neurons, the bipolar cells, which relay information in parallel to the inner retina. In the inner retina, these parallel streams not only contribute to conscious vision but also to subconscious processes like gaze stabilization.
***
"Using these techniques, the investigators showed that certain bipolar cell types respond to individual fusion events and total quanta while other types respond to degrees of locally coincident events, creating a nonlinear summation. These differences are caused by a combination of factors specific to each bipolar cell type, including diffusion distance, contact number, receptor affinity, and proximity to transporters.
"'The outer retina uses the same toolbox as elsewhere in the central nervous system, like vesicles, synaptic release zones and postsynaptic receptors, but organizes these elements in novel ways to accomplish a different, very localized type of processing. Analog processing is also found in the dendritic tree of central nervous system neurons, where the bulk of calculation, both linear and nonlinear, occurs," DeVries said.
"According to DeVries, one next step for his team includes using a new, more powerful type of super-resolution microscopy to determine the protein components that make up cone synapses.
"'One of the ways that the different bipolar cells divide the cone signal up is that some of them are very sensitive to small signals and others require strong signals to respond; the 'strong signal' or high threshold bipolar cell has a unique type of insensitive post-synaptic receptor. We would also like to identify this receptor," DeVries said."
comment: We know eyes evolved from light sensing spots of cells, but how this degree of intricate design developed implies a designer was necessary,
Biochemical controls: cell conversion controls
by David Turell , Thursday, June 29, 2023, 17:19 (97 days ago) @ David Turell
A study of biochemical steps:
https://www.sciencedaily.com/releases/2023/06/230627225200.htm
"Central to the study is C/EBPα (CCAAT/enhancer-binding protein alpha), a protein that orchestrates the conversion of B lymphocytes to macrophages, another type of immune cell. C/EBPα is a transcription factor, a type of protein which binds to specific DNA sequences in the regulatory regions of genes to influence the rate of transcription, the first step that leads to the activation or silencing of protein expression. Transcription factors play a vital role in the transformation of one cell type to another during differentiation and development, as well as in the growth and function of cells.
"Like many other proteins, C/EBPα is modified by enzymes, for example through the addition of a methyl group to specific amino acids. These modifications can have significant effects on interactions of the protein. The researchers found that when one specific arginine residue of C/EBPα is left unmethylated, it greatly accelerates the conversion process of B lymphocytes to macrophages.
"The study also found that the methylation of this specific arginine residue is mediated by the enzyme Carm1. Previous research has shown that Carm1-deficient mice are resistant to induced forms of acute myeloid leukaemia. The researchers hypothesise that the mechanisms they uncover in the present study can explain why: the unmethylated version of C/EBPα is a stronger inducer of macrophage differentiation compared to its methylated counterpart. As macrophages are a non-dividing cell type, this could prevent the formation of cancer cells.
***
"To induce a cell conversion, C/EBPα works by interacting with another transcription factor called PU.1, which itself is essential for the development of immune cells and is already expressed in B cells. C/EBPαR35A had a much higher interaction affinity with PU.1, increasing the speed by which the combination of the two proteins silence the genes associated with B cells and activate the genes associated with macrophages.
"The methylation of C/EBPα is an example of an epigenetic mechanism. These are mechanisms which modify how the genome -- the instruction manual inside every cell of the human body -- is read. "Drugs that affect epigenetic mechanisms as described in the present study may indeed alter the function of transcription factors and correct cells that went astray, such as seen in cancer and leukaemia," says Dr. Achim Leutz, senior author from the Max-Delbrück-Center.
"'In this novel mechanism PU.1 is triggered by C/EBPα to switch from a B cell regulator into a macrophage regulator, an elegant 'on-off' mechanism that ensures the faithful formation of a mature cell type, avoiding the formation of 'confused' cells often seen in blood cancers. Therefore, drugs might be found that target this mechanism to correct such defects" adds Dr. Leutz."
Comment: this is a look into how cells convert themselves biochemically. This is what stem cells do as a source for all cell types. It requires specific enzyme activity. Enzymes are giant specifically designed molecules to force reactions to occur. A cell conversion in form requires all these exact steps working together. It must appear through evolution in complete form. Stepwise formation is impossible by chance innovation. It is evidence of a design by a designer.
Biochemical controls: cell life or death controls
by David Turell , Friday, June 30, 2023, 15:13 (97 days ago) @ David Turell
AMP plays a major role:
https://www.sciencemagazinedigital.org/sciencemagazine/library/item/30_june_2023/411229...
"Maintenance of size and shape of organs in multicellular organisms is determined by the balance between cell proliferation and cell death. It was thought that apoptosis, a mechanism driven by cleavage of intracellular proteins by caspases, was the only genetically programmed cell death pathway. However, it became apparent that necrosis, once regarded merely as an accidental form of cell death, can be a regulated process, with necroptosis being the major subtype. A key player in both apoptosis and necroptosis is receptor-interacting protein kinase 1 (RIPK1). Zhang et al. report that the cellular energy sensor adenosine monophosphate (AMP)–activated protein kinase (AMPK) phosphorylates and inactivates RIPK1, opposing necroptosis and thus promoting cell survival.
"During apoptosis, cell fragments are removed by phagocytic cells in an immunologically silent manner, whereas during necroptosis, cells burst, triggering inflammation. The latter might seem deleterious—indeed, necroptosis is implicated in several inflammatory disorders in humans. However, it has been suggested that necroptosis may have arisen as a backup pathway to kill virus-infected cells, in which viral proteins sometimes inhibit apoptosis.
***
"AMPK is expressed in nearly all eukaryotic cells and is switched on by cellular energy stress that it normally senses by detecting increases in AMP relative to ATP (see the figure), although glucose starvation can also be sensed by an AMP-independent mechanism (6). AMPK then phosphorylates numerous downstream target proteins (7), switching on catabolic pathways that generate ATP from adenosine diphosphate (ADP) while switching off ATP-consuming processes, thus preserving cellular energy status and promoting survival.
***
"It is becoming apparent that a major function of AMPK is to maintain cellular mitochondrial networks, which are the main source of ATP. When a mitochondrial network becomes damaged, it must first be cleaved into segments small enough to be removed by mitophagy, which AMPK achieves by promoting fission and inhibiting fusion of mitochondria through the phosphorylation of mitochondrial fission factor (MFF) and mitochondrial fission regulator 1 like (MTFR1L), respectively. Next, AMPK activates mitophagy by phosphorylating unc-51–like autophagy-activating kinase (ULK1). Finally, by phosphorylating folliculin-interacting protein 1 (FNIP1), AMPK stimulates both lysosomal and mitochondrial biogenesis—the former to ensure an adequate supply of lysosomes to support mitophagy, and the latter to replace damaged mitochondrial components that had been recycled by mitophagy. How does this fit in with the findings of Zhang et al.? In the longer term, maintenance of the mitochondrial network by AMPK would help to ensure cellular energy homeostasis, thus making it less likely that necroptosis would be promoted by ATP depletion. However, if necroptosis was triggered, the phosphorylation of RIPK1 by AMPK might delay the process to allow time for repair of the mitochondrial network and stave off cell death."
Comment: I've left out the major biochemical discussions of molecular reaction pathways. This yes or no monitoring of cell survival or death is very precise and very complex. It cannot be developed stepwise, so it must be designed all at once, as it is irreducibly complex.
Biochemical controls: plant wound signals
by David Turell , Saturday, October 22, 2022, 16:57 (347 days ago) @ David Turell
How plants signal damage:
https://phys.org/news/2022-10-science-register-trauma-precursor-calcium.html
"John Innes Center researchers have shown that calcium waves are not a primary response, but rather they are a secondary response to a wave of amino acids released from the wound.
***
"It has been observed for many years that wounding, and other trauma, initiates calcium waves that travel both short distances from cell to cell, and longer distances from leaf to leaf.
"These calcium waves are reminiscent of signaling seen in the nerves in mammals, but since plants do not have nerve cells, the mechanism by which this happens has been in question.
The new findings, which appear in Science Advances, suggest that when a cell is wounded, it releases a wave of glutamate, an amino acid. As this wave travels through plant tissues, it activates calcium channels in the membranes of the cells it passes. This activation appears like a calcium wave but is a passive response, or "readout'' of the moving glutamate signal.
***
"Dr. Faulkner's group specializes in the study of plasmodesmata, the channels or bridges that connect cells and the team speculated that a wound signal would travel from cell to cell through plasmodesmata. However, using quantitative imaging techniques, data modeling and genetics they found that the mobile signal is a glutamate wave that travels outside of cells, along the cell walls.
""The glutamate and calcium waves are connected—glutamate triggers the calcium response. You could imagine it with an analogy of a corridor. The glutamate rushes down the corridor and as it passes a door it kicks it open. The calcium response is the door opening. Up to now the assumption has been that what moved down the corridor was hydraulic pressure or a series of propagating chemical reactions, but our study shows that this is not the case," said Dr. Faulkner."
Comment: a different way to spread information without nerves.