Microevolution is better described as adaptation and is an engineered process, which does not happen by accident. The Cell receives macroscopic signals from the environment and responds by adaptive, nonrandom mutations. The capacity of Mammals and other multicellular organisms to adapt to changing environmental conditions is extraordinary. In order to effectively produce and secrete mature proteins, cellular mechanisms for monitoring the environment are essential. Exposure of cells to various environmental causes accumulation of unfolded proteins and results in the activation of a well-orchestrated set of pathways during a phenomenon known as the unfolded protein response (UPR). Cells have powerful quality control networks consisting of chaperones and proteases that cooperate to monitor the folding states of proteins and to remove misfolded conformers through either refolding or degradation. Free-living organisms, which are more directly exposed to environmental fluctuations, must often survive even harsher folding stresses. These stresses not only disrupt the folding of newly synthesized proteins but can also cause misfolding of already folded proteins. In living organisms, robustness is provided by homeostatic mechanisms. At least five epigenetic mechanisms are responsible for these life-essential processes :
- heat shock factors (HSFs)
- The unfolded protein response (UPR)
- nonhomologous end-joining and homologous recombination
- The DNA Damage Response
- The Response to Oxidative Stress
The cell modulates the signalling pathways at transcriptional, post-transcriptional and post-translational levels. Complex signalling pathways contribute to the maintenance of systemic homeostasis. Homeostasis is the mechanistic fundament of living organisms.
Homeostasis, from the Greek words for "same" and "steady," refers to any process that living things use to actively maintain fairly stable conditions necessary for survival. It is also synonymous with robustness and adaptability.
This essential characteristic of living cells, homeostasis, is the ability to maintain a steady and more-or-less constant chemical balance in a changing environment. Cell survival requires appropriate proportions of molecular oxygen and various antioxidants. Reactive products of oxygen, calles Reactive Oxygen Species ( ROS) are amongst the most potent and omnipresent threats faced by cells. Cells, damaged by ROS, irreversibly infected, functionless and/or potentially oncogenic cells are destined for persistent inactivation or elimination, respectively. If mechanisms that do not trigger controlled and programmed Cell death ( apoptosis) are not present at day 1, the organisms cannot survive and dies. Simply put, the principle is that all of a multicellular organism's cells are prepared to suicide when needed for the benefit of the organism as a whole. They eliminate themselves in a very carefully programmed way so as to minimize damage to the larger organism. On average, in human adults, it’s about 50-70 BILLION cells that die per day. We shed 30,000 to 50,000 skin cells every minute.
1. The control of metabolism is a fundamental requirement for all life, with perturbations of metabolic homeostasis underpinning numerous disease-associated pathologies.
2. Any incomplete Metabolic network without the control mechanisms in place to get homeostasis would mean disease and cell death.
3. A minimal metabolic network and the control mechanisms had to be in place from the beginning, which means, and gradualistic explanation of the origin of biological Cells, and life is unrealistic.
Life is an all or nothing business and points to a creative act of God.
Following molecules must stay in a finely tuned order and balance for life to survive:
- Halogens like chlorine, fluoride, iodine, and bromine. The body needs to maintain a delicate balance between all these elements.
- Molybdenum (Mo) and iron (Fe) are essential micronutrients required for crucial enzyme activities and mutually impact their homeostasis, which means, they are interdependent on each other to maintain homeostatic levels.
- Potassium plays a key role in maintaining cell function, and it is important in maintaining fluid and electrolyte balance. Potassium-40 is probably the most dangerous light radioactive isotope, yet the one most essential to life. Its abundance must be balanced on a razor’s edge.
- The ability of cells to maintain a large gradient of calcium across their outer membrane is universal. All biological cells have a low cytosolic (liquid found inside Cells ) calcium concentration, can and must keep this even when the free calcium outside is up to 20,000 times higher concentrated!
- Nutrient uptake and homeostasis must be adjusted to the needs of the organisms according to developmental stages and environmental conditions.
- Magnesium is the second most abundant cellular cation after potassium. The concentrations are essential to regulate numerous cellular functions and enzymes
- Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport
- Phosphate, as a cellular energy currency, essentially drives most biochemical reactions defining living organisms, and thus its homeostasis must be tightly regulated.
- Zinc (Zn) is an essential heavy metal that is incorporated into a number of human Zn metalloproteins. Zn plays important roles in nucleic acid metabolism, cell replication, and tissue repair and growth. Zn contributes to intracellular metal homeostasis.
- Selenium homeostasis and antioxidant selenoproteins in the brain: lack of finetuned balance has implications for disorders in the central nervous system
- Copper ion homeostasis is maintained through regulated expression of genes involved in copper ion uptake.
In the early 1960s, Ernest Nagel and Carl Hempel showed that self-regulated systems are teleological.
In his book: THE TINKERER’S ACCOMPLICE, How Design Emerges from Life Itself J . SCOTT. TURNER, writes at page 12 :
Although I touch upon ID obliquely from time to time, I do so not because I endorse it, but because it is mostly unavoidable. ID theory is essentially warmed-over natural theology, but there is, at its core, a serious point that deserves serious attention. ID theory would like us to believe that some overarching intelligence guides the evolutionary process: to say the least, that is unlikely. Nevertheless, how design arises remains a very real problem in biology. My thesis is quite simple: organisms are designed not so much because natural selection of particular genes has made them that way, but because agents of homeostasis build them that way. These agents’ modus operandi is to construct environments upon which the precarious and dynamic stability that is homeostasis can be imposed, and design is the result.
The author does not identify these agents, but Wiki describes agents as CONSCIOUS beings, which act with specific goals in mind. In the case of life, this agent made it possible for biological cells to actively maintain fairly stable levels of various metabolites and molecules, necessary for survival. We are once more, upon careful examination of the evidence in nature, justified to infer an intelligent designer as most case-adequate explanation of the origin of homeostasis and the ability of adaptation, commonly called evolution, of all living organisms.
Signaling pathways and regulators of PRRs.
Pattern-recognition receptors (PRRs) share intracellular pathways that lead to the production of pro-inflammatory cytokines and type I interferons (IFNs).
a | All the Toll-like receptors (TLRs), except for TLR3, interact with MYD88 to induce the activation of nuclear factor-κB (NF‑κB) and mitogen-activated protein kinases (MAPKs), which induce the transcription factor activator protein 1 (AP-1), for the induction of pro-inflammatory cytokine expression. The TIR domain-containing adaptor protein inducing IFNβ (TRIF) pathway is shared by TLR4 and TLR3, and induces the activation of interferon regulatory factors IRF3–IRF7 for the production of type I IFNs.
b | Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) first interact with mitochondrial antiviral signaling protein (MAVS) and then activate signaling cascades through stimulator of interferon genes (STING) and TANK-binding kinase 1 (TBK1), leading to the expression of type I IFNs. MAVS also signals through receptor-interacting serine/threonine protein kinase 1 (RIPK1) for AP‑1 activation.
c | Many cytosolic DNA and RNA sensors, including cyclic GMP–AMP synthase (cGAS), double-strand break repair protein MRE11, IFNγ-inducible protein 16 (IFI16), DNA-dependent protein kinase (DNA‑PK), the probable ATP-dependent RNA helicases DDX41 and DDX60, leucine-rich repeat flightless interacting protein 2 (LRRFIP2) and protein kinase RNA-activated (PKR), recognize intracellular DNA or RNA and converge on STING to drive type I IFNs and cytokine production. The ATP-dependent RNA helicases DHX9 and DHX36 recognize CpG-containing DNA and induce the MYD88‑dependent signalling pathway.
d | NOD-like receptors (NLRs) are activated upon cellular infection or stress, and engage innate immune responses via RIPK2–NF‑κB signalling activation. Some NLRs, such as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), ICE protease-activating factor (IPAF) and NLR apoptosis inhibitory protein 5 (NAIP5), form inflammasomes that contain the apoptosis-associated speck-like protein containing a CARD (ASC) and caspase 1, and trigger the maturation of interleukin-1β (IL-1β). 4
Last edited by Otangelo on Thu Dec 10, 2020 9:13 am; edited 3 times in total