#] #] ********************* #] "$d_web"'Neural nets/MindCode/0_MindGene notes.txt' - mRNA [codon, program, mechanism, etc] # www.BillHowell.ca 04Nov2023 initial # view in text editor, using constant-width font (eg courier), tabWidth = 3 see : "$d_web"'Neural nets/MindCode/0_MindCode & callerID-SNNs.links.txt' #48************************************************48 #24************************24 # Table of Contents, generate with : # $ grep "^#]" "$d_web"'Neural nets/MindCode/0_MindGene notes.txt' | sed "s/^#\]/ /" # ********************* "$d_web"'Neural nets/MindCode/0_MindGene notes.txt' - mRNA [codon, program, mechanism, etc] Setup, ToDos, 07Nov2023 update process : +-----+ 10Nov2023 cat digiVoice, file-away 08Nov2023 emrep Juyang Weng 08Nov2023 emrep Juyang Weng - link didn't work 08Nov2023 add [Proteomic, Neuroinformatic]s * [voice, section] 07Nov2023 search "Corona virus mRNA vaccine and Shapiro and Benenson" >> nothing 07Nov2023 search "Corona virus mRNA vaccine and Israeli scientists" 07Nov2023 MindCode: online upload [addition, change]s 07Nov2023 split voice recording 05Nov2023 Shapiro & Benenson 02Nov2023 search "DNA transcription software" 02Nov2023 DNA, RNA, mRNA 07Mar2018 DNA storage for real computers 23Sep2019 HOX genes (architecture) 11Aug2019 Architectures & Function 10Aug2019 mRNA circulation - soma to synapse 25Jul2019 Alice Parker. Spiking Neural Networks & DNA. USC. Los Angeles 07Mar2018 DNA storage for real computers #24************************24 #] Setup, ToDos, #] 07Nov2023 update process : new webPages: TableOfContents each new webPage : bash "$d_bin"'fileops run webSite.sh' manually add to pHtmlPathAll_L.txt use auto update and checks from time-to-time "$d_PROJECTS"'bin - secure/lftp update entire webSite.sh' # onLine update dWebAll_upload_online pWebPageL_upload_online 14:50$ bash "$d_PROJECTS"'bin - secure/lftp update entire webSite.sh' dWebAll_upload_online... >> 08Nov2023 : dWebAll : 21min, 2 voice files webPageL : 2m07s, one WebPage, 2 pMenuTops #] +-----+ #24************************24 #08********08 #] ??Dec2023 #08********08 #] 18Dec2023 Gerald Pollock - mechanism tat "walks" along micro-tubules #08********08 #] ??Dec2023 #08********08 #] ??Dec2023 #08********08 #] ??Dec2023 #08********08 #] ??Dec2023 #08********08 #] ??Dec2023 #08********08 #] 19Dec2023 search "biochemical, physical RNA mechanisms" key previous comment below 19Dec2023 : >> shows path to DNA: "... YAP/TAZ is translocated into the nucleus to promote the transcription of downstream genes, collagen synthesis, and cell differentiation ..." +-----+ RNA Polymerase and Transcription Mechanisms: The Forefront of Physicochemical Studies of Chemical Reactions 29Dec2020 Nobuo Shimamoto, Masahiko Imashimizu; Biomolecules. 2021 Jan; 11(1): 32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823607/ >> IMPORTANT! re-read this!!! >> also - Peter Erdi's non-equilibrium checistry, or something like that... Abstract The study of transcription and its regulation is an interdisciplinary field that is closely connected with genetics, structural biology, and reaction theory. Among these, although less attention has been paid to reaction theory, it is becoming increasingly useful for research on transcription. Rate equations are commonly used to describe reactions involved in transcription, but they tend to be used unaware of the timescales of relevant physical processes. In this review, we discuss the limitation of rate equation for describing three-dimensional diffusion and one-dimensional diffusion along DNA. We then introduce the chemical ratchet mechanism recently proposed for explaining the antenna effect, an enhancement of the binding affinity to a specific site on longer DNA, which deviates from a thermodynamic rule. We show that chemical ratchet cannot be described with a single set of rate equations but alternative sets of rate equations that temporally switch no faster than the binding reaction. Keywords: transcriptional regulation, reaction theory, prediction of promoters, one-dimensional diffusion, rate equation, detailed balance, antenna effect, physicochemical techniques >> Cool - like the mis-direction of statistical models!!!???!!! Another historical event in the study of transcription was the early discovery of an initiation factor, the E. coli sigma-70 subunit. Sigma-70 is able to activate the synthesis of most native transcripts, contributing to reconstitution with purified factors and the identification of promoters. The construction of a fully active reconstitution system was initially expected to deductively interpret physiological phenomena in chemical and physical terms, thereby unifying the basic principles of biology, chemistry, and physics. Contrary to this expectation, mechanistic studies have been inductive rather than deductive. ... As in other biological processes, transcription is composed of chemical reactions. Notably, there are several basic requirements for a chemical reaction to be described with a rate equation [9]. As will be discussed below in detail, a bimolecular association process mediated by diffusion can be described with rate equations in some cases. However, the transfer itself is beyond the description with rate equations. Furthermore, consideration of the timescales of reactions is critical since timescale matching is essential for the functions of regulators to be expressed, as will be discussed later. Until recently, the mechanism of the chemical ratchet had been overlooked because of the lack of these notions. However, understanding the foundation of scientific tools is essential to promote soundness and clarity in science. +-----+ https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(OpenStax)/10%3A_Biochemistry_of_the_Genome/10.03%3A_Structure_and_Function_of_RNA >> One of best descriptions I';ve seen yet - very astute comments!!! Figure 10.3.1 10.3. 1: (a) Ribonucleotides contain the pentose sugar ribose instead of the deoxyribose found in deoxyribonucleotides. (b) RNA contains the pyrimidine uracil in place of thymine found in DNA. The RNA-specific pyrimidine uracil forms a complementary base pair with adenine and is used instead Structurally speaking, ribonucleic acid (RNA) , is quite similar to DNA . However, whereas DNA molecules are typically long and double stranded, RNA molecules are much shorter and are typically single stranded. RNA molecules perform a variety of roles in the cell but are mainly involved in the process of protein synthesis (translation) and its regulation. RNA Structure RNA is typically single stranded and is made of ribonucleotides that are linked by phosphodiester bonds . A ribonucleotide in the RNA chain contains ribose (the pentose sugar), one of the four nitrogenous bases (A, U, G, and C), and a phosphate group. The subtle structural difference between the sugars gives DNA added stability, making DNA more suitable for storage of genetic information, whereas the relative instability of RNA makes it more suitable for its more short-term functions. /home/bill/web/Neural nets/MindCode/images/RNA [pentose sugar ribose, uracil], DNA [deoxyribose sugar, thymine] dateUnknown libretexts biology.png The RNA-specific pyrimidine uracil forms a complementary base pair with adenine and is used instead of the thymine used in DNA . Even though RNA is single stranded, most types of RNA molecules show extensive intramolecular base pairing between complementary sequences within the RNA strand, creating a predictable three-dimensional structure essential for their function (Figure 10.3.1 and Figure 10.3.2). /home/bill/web/Neural nets/MindCode/images/RNA single strand predictable three-dimensional structure essential for function, DNA double strand dateUnknown libretexts biology.png In 1961, French scientists François Jacob and Jacques Monod hypothesized the existence of an intermediary between DNA and its protein products, which they called messenger RNA.1 Evidence supporting their hypothesis was gathered soon afterwards showing that information from DNA is transmitted to the ribosome for protein synthesis using mRNA . If DNA serves as the complete library of cellular information, mRNA serves as a photocopy of specific information needed at a particular point in time that serves as the instructions to make a protein. The mRNA carries the message from the DNA , which controls all of the cellular activities in a cell. If a cell requires a certain protein to be synthesized, the gene for this product is “turned on” and the mRNA is synthesized through the process of transcription (see RNA Transcription ). The mRNA then interacts with ribosomes and other cellular machinery (Figure 10.3.3 ) to direct the synthesis of the protein it encodes during the process of translation (see Protein Synthesis). mRNA is relatively unstable and short-lived in the cell, especially in prokaryotic cells, ensuring that proteins are only made when needed. /home/bill/web/Neural nets/MindCode/images/[mRNA, tRNA] are used in protein synthesis dateUnknown libretexts biology.png /home/bill/web/Neural nets/MindCode/images/tRNA is a single-stranded molecule with significant intracellular base pairing, characteristic three-dimensional shape dateUnknown libretexts biology.png /home/bill/web/Neural nets/MindCode/z_Archive/231219 15h15m tble: Structure and Function of RNA.html

Table 10.3.1: Structure and Function of RNA
mRNA rRNA tRNA
Structure Short, unstable, single-stranded
RNA corresponding to a gene encoded within DNA 		Longer, stable RNA molecules composing 60% of ribosome’s mass Short (70-90 nucleotides)
stable RNA with extensive intramolecular base pairing;
contains [amino acid, mRNA] binding sites
Function Serves as intermediary between DNA and protein;
used by ribosome to direct synthesis of protein it encodes 		Ensures the proper alignment of mRNA, tRNA, and ribosome during protein synthesis;
catalyzes peptide bond formation between amino acids 		Carries the correct amino acid to the site of protein synthesis in the ribosome
#08********08 #] 19Dec2023 search "biochemical signaling mechanisms" +-----+ Molecular insights into the biochemical functions and signalling mechanisms of plant NLRs 30Mar2022 Xiaoxiao Liu, Li Wan; Mol Plant Pathol. 2022 Jun; 23(6): 772–780; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104254/ Abstract Plant intracellular immune receptors known as NLR (nucleotide-binding leucine-rich repeat) proteins confer immunity and cause cell death. Plant NLR proteins that directly or indirectly recognize pathogen effector proteins to initiate immune signalling are regarded as sensor NLRs. Some NLR protein families function downstream of sensor NLRs to transduce immune signalling and are known as helper NLRs. Recent break- through studies on plant NLR protein structures and biochemical functions greatly advanced our understanding of NLR biology. Comprehensive and detailed knowledge on NLR biology requires future efforts to solve more NLR protein structures and in- vestigate the signalling events between sensor and helper NLRs, and downstream of helper NLRs. >> great article!! apparantly started excitement for NLRs? /home/bill/web/References/Neural Nets/MindCode/Molecular insights into the biochemical functions and signalling mechanisms of plant NLRs 30Mar2022 Liu, Wan.pdf +-----+ Xingpeng Di, Xiaoshuai Gao, Liao Peng, Jianzhong Ai, Xi Jin, Shiqian Qi, Hong Li, Kunjie Wang, Deyi Luo 11May2023 Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets, Signal Transduction and Targeted Therapy volume 8, Article number: 282 (2023) https://www.nature.com/articles/s41392-023-01501-9 Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism. Typical mechanical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, and extracellular fluid viscosity. Mechanotransduction has been expected to trigger multiple biological processes, such as embryonic development, tissue repair and regeneration. However, prolonged excessive mechanical stimulation can result in pathological processes, such as multi-organ fibrosis, tumorigenesis, and cancer immunotherapy resistance. Although the associations between mechanical cues and normal tissue homeostasis or diseases have been identified, the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated, and no effective therapies are currently available targeting mechanical cue-related signaling. This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence. The key effectors responding to mechanical stimulations are listed, such as Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator with PDZ-binding motif (TAZ), and transient receptor potential vanilloid 4 (TRPV4). We also reviewed the key signaling pathways, therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues. /home/bill/web/References/Neural Nets/MindCode/Di, Gao, etal 11May2023 Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets.pdf /home/bill/web/Neural nets/MindCode/images/Di, Gao, etal 11May2023 Fig3 Regulatory mechanisms of tensile force, hydrostatic pressure, and shear stress on different cell types.jpg /home/bill/web/Neural nets/MindCode/images/Di, Gao, etal 11May2023 Fig4 Cellular mechanotransduction of ECM stiffness.png >> shows path to DNA: "... YAP/TAZ is translocated into the nucleus to promote the transcription of downstream genes, collagen synthesis, and cell differentiation ..." /home/bill/web/Neural nets/MindCode/images/Di, Gao, etal 11May2023 Fig5 Mechanisms of integrins responding to mechanical stimulation.png +------+ https://www.sciencedirect.com/science/article/pii/S1097276521005980 Molecular mechanisms of early plant pattern-triggered immune signaling Molecular Cell, Volume 81, Issue 17, 2021, pp. 3449-3467 Thomas A. DeFalco, Cyril Zipfel >> cool!! >> Gerald Pollack: ion channels don't maintain electrochemical potential gaps across cell membrane. Is this an illustration of real reason for Ca2+ ion channels? /home/bill/web/References/Neural Nets/MindCode/DeFalco, Zipfel ddmmm2021 Molecular mechanisms of early plant pattern-triggered immune signaling.pdf +-----+ https://www.sciencedirect.com/science/article/pii/S1674205222004117 Molecular Plant, Volume 16, Issue 1, 2 January 2023, Pages 75-95 Review article Structure, biochemical function, and signaling mechanism of plant NLRs Jizong Wong, Wen Song, Jijie Chai /home/bill/web/Neural nets/MindCode/images/Wong, Song, Chai 02Jan2023 Fig 1 plant immune system and signalling network 99kb.jpg /home/bill/web/Neural nets/MindCode/images/Wong, Song, Chai 02Jan2023 Fig 1 plant immune system and signalling network 739kb.jpg /home/bill/web/References/Neural Nets/MindCode/Wong, Song, Chai 02Jan2023 Structure, biochemical function, and signaling mechanism of plant NLRs.pdf >> AWESOME biochem diagrams, explanations Abstract To counter pathogen invasion, plants have evolved a large number of immune receptors, including membrane-resident pattern recognition receptors (PRRs) and intracellular nucleotide-binding and leucine-rich repeat receptors (NLRs). Our knowledge about PRR and NLR signaling mechanisms has expanded significantly over the past few years. Plant NLRs form multi-protein complexes called resistosomes in response to pathogen effectors, and the signaling mediated by NLR resistosomes converges on Ca2+-permeable channels. Ca2+-permeable channels important for PRR signaling have also been identified. These findings highlight a crucial role of Ca2+ in triggering plant immune signaling. In this review, we first discuss the structural and biochemical mechanisms of non-canonical NLR Ca2+ channels and then summarize our knowledge about immune-related Ca2+-permeable channels and their roles in PRR and NLR signaling. We also discuss the potential role of Ca2+ in the intricate interaction between PRR and NLR signaling. Introduction The plant immune system mainly relies on two types of receptors to mediate immune responses. One type is cell-surface-located pattern recognition receptors (PRRs) sensing the conserved signatures of invading pathogens, called pathogen-associated molecular patterns (PAMPs) or host-derived damage-associated molecular patterns (DAMPs), to initiate pattern-triggered immunity (PTI) (Yu et al., 2017; DeFalco and Zipfel, 2021). The other type is intracellular nucleotide-binding (NB), leucine-rich repeat (LRR) receptors (NLRs). Plant NLRs mediate direct or indirect recognition of race-specific pathogen effectors delivered into plant cells, initiating effector-triggered immunity (ETI) (Cui et al., 2015; Jones et al., 2016; Zhou and Zhang, 2020). Despite their different structures and subcellular localizations, PRRs and NLRs share a suite of downstream defense responses, including Ca2+ influx; bursts of reactive oxygen species (ROS); activation of mitogen-activated protein kinase (MAPK) cascades; production of phytocytokines and defense hormones, including salicylic acid (SA) and ethylene; and massive transcriptional reprogramming (Ngou et al., 2022; Figure 1). Probably because of their similarity, PTI and ETI are tightly connected and mutually potentiate (Ngou et al., 2021; Yuan et al., 2021). However, PTI and ETI differ in timing, amplitude, and duration of defense. Compared with PTI, ETI involves prolonged and more robust immune responses and is frequently accompanied by a hypersensitive response (HR), a form of localized programmed cell death associated with pathogen restriction or killing. The pathogen resistance and cell death activity of the plant HR can be physiologically, genetically and temporally uncoupled (Künstler et al., 2016). +-----+ https://www.khanacademy.org/science/ap-biology/cell-communication-and-cell-cycle/cell-communication/a/introduction-to-cell-signaling Overview of cell signaling Cells typically communicate using chemical signals. These chemical signals, which are proteins or other molecules produced by a sending cell, are often secreted from the cell and released into the extracellular space. There, they can float – like messages in a bottle – over to neighboring cells. Sending cell: this cell secretes a ligand. Target cell: this cell has a receptor that can bind the ligand. The ligand binds to the receptor and triggers a signaling cascade inside the cell, leading to a response. Nontarget cell: this cell does not have a receptor for the ligand (though it may have other kinds of receptors). The cell does not perceive the ligand and thus does not respond to it. Sending cell: this cell secretes a ligand. Target cell: this cell has a receptor that can bind the ligand. The ligand binds to the receptor and triggers a signaling cascade inside the cell, leading to a response. Nontarget cell: this cell does not have a receptor for the ligand (though it may have other kinds of receptors). The cell does not perceive the ligand and thus does not respond to it. Not all cells can “hear” a particular chemical message. In order to detect a signal (that is, to be a target cell), a neighbor cell must have the right receptor for that signal. When a signaling molecule binds to its receptor, it alters the shape or activity of the receptor, triggering a change inside of the cell. Signaling molecules are often called ligands, a general term for molecules that bind specifically to other molecules (such as receptors). The message carried by a ligand is often relayed through a chain of chemical messengers inside the cell. Ultimately, it leads to a change in the cell, such as alteration in the activity of a gene or even the induction of a whole process, such as cell division. Thus, the original intercellular (between-cells) signal is converted into an intracellular (within-cell) signal that triggers a response. #08********08 #] 18Dec2023 search "Endocrine signals via hormones" +-----+ https://www.healthline.com/health/the-endocrine-system#function Endocrine System Overview Medically reviewed by Marina Basina, M.D. By Jill Seladi-Schulman, Ph.D. — Updated on March 12, 2022 What does the endocrine system do? The endocrine system is responsible for regulating a range of bodily functions through the release of hormones. Hormones are secreted by the glands of the endocrine system, traveling through the bloodstream to various organs and tissues in the body. The hormones then tell these organs and tissues what to do or how to function. Some examples of bodily functions that are controlled by the endocrine system include: metabolism growth and development sexual function and reproduction heart rate blood pressure appetite sleeping and waking cycles body temperature What is a gland? A gland is an organ that creates and releases substances that the body needs to function. There are two types of glands: endocrine glands, which release hormones directly into the bloodstream exocrine glands, like lymph nodes and sweat glands, which are not part of the endocrine system Organs in the endocrine system The glands of the endocrine system are where hormones are produced, stored, and released. Each gland produces one or more hormones, which go on to target specific organs and tissues in the body. The glands of the endocrine system include the: Hypothalamus. While some people don’t consider it a gland, the hypothalamus produces multiple hormones that control the pituitary gland. It’s also involved in regulating many functions, including sleep-wake cycles, body temperature, and appetite. It can also regulate the function of other endocrine glands. Pituitary. The pituitary gland is located below the hypothalamus. The hormones it produces affect growth and reproduction. They can also control the function of other endocrine glands. Pineal. This gland is found in the middle of your brain. It’s important for your sleep-wake cycles. Thyroid. The thyroid gland is located in the front part of your neck. It’s very important for metabolism. Parathyroid. Also located in the front of your neck, the parathyroid gland is important for maintaining control of calcium levels in your bones and blood. Thymus. Located in the upper torso, the thymus is active until puberty and produces hormones that are important for the development of a type of white blood cell called a T cell. Adrenal. One adrenal gland can be found on top of each kidney. These glands produce hormones that are important for regulating functions such as blood pressure, heart rate, and stress response. Pancreas. The pancreas is located in your abdomen behind your stomach. Its endocrine function involves controlling blood sugar levels. Some endocrine glands also have non-endocrine functions. For example, the ovaries and testes produce hormones, but they also have the non-endocrine function of producing eggs and sperm, respectively. Endocrine system hormones Hormones are the chemicals the endocrine system uses to send messages to organs and tissue throughout the body. Once released into the bloodstream, hormones travel to their target organ or tissue, which has receptors that recognize and react to the hormone. Below are some examples of hormones that are produced by the endocrine system. Hormone Secreting gland(s) Function adrenaline adrenal increases blood pressure, heart rate, and metabolism in reaction to stress aldosterone adrenal controls the body’s salt and water balance cortisol adrenal plays a role in stress response dehydroepiandrosterone sulfate (DHEA-S) adrenal aids in production of body odor and growth of body hair during puberty estrogen ovary works to regulate the menstrual cycle, maintain pregnancy, and develop female sex characteristics; aids in sperm production follicle-stimulating hormone (FSH) pituitary controls the production of eggs and sperm glucagon pancreas helps increase levels of blood glucose (blood sugar) insulin pancreas helps reduce your blood glucose levels luteinizing hormone (LH) pituitary controls estrogen and testosterone production as well as ovulation melatonin pineal controls sleep-wake cycles oxytocin pituitary helps with lactation, childbirth, and mother-child bonding parathyroid hormone parathyroid controls calcium levels in bones and blood progesterone ovary helps prepare the body for pregnancy when an egg is fertilized prolactin pituitary promotes breast-milk production testosterone ovary, teste, adrenal contributes to sex drive and body density in males and females as well as development of male sex characteristics thyroid hormone thyroid helps control several body functions, including the rate of metabolism and energy levels Endocrine system diagram Explore the interactive 3-D diagram below to learn more about the endocrine system. #08********08 #] 18Dec2023 biochemical [signaling, cascades] +-----+ https://en.wikipedia.org/wiki/Biochemical_cascade Biochemical cascade A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that is transduced to the cell interior through second messengers which amplify the signal and transfer it to effector molecules, causing the cell to respond to the initial stimulus.[1] Most biochemical cascades are series of events, in which one event triggers the next, in a linear fashion. At each step of the signaling cascade, various controlling factors are involved to regulate cellular actions, in order to respond effectively to cues about their changing internal and external environments.[1] Transductors and effectors Signal transduction is realized by activation of specific receptors and consequent production/delivery of second messengers, such as Ca2+ or cAMP. These molecules operate as signal transducers, triggering intracellular cascades and in turn amplifying the initial signal.[4] Two main signal transduction mechanisms have been identified, via nuclear receptors, or via transmembrane receptors. In the first one, first messenger cross through the cell membrane, binding and activating intracellular receptors localized at nucleus or cytosol, which then act as transcriptional factors regulating directly gene expression. This is possible due to the lipophilic nature of those ligands, mainly hormones. In the signal transduction via transmembrane receptors, the first messenger binds to the extracellular domain of transmembrane receptor, activating it. These receptors may have intrinsic catalytic activity or may be coupled to effector enzymes, or may also be associated to ionic channels. Therefore, there are four main transmembrane receptor types: G protein coupled receptors (GPCRs), tyrosine kinase receptors (RTKs), serine/threonine kinase receptors (RSTKs), and ligand-gated ion channels (LGICs).[1][4] Second messengers can be classified into three classes: 1. Hydrophilic/cytosolic – are soluble in water and are localized at the cytosol, including cAMP, cGMP, IP3, Ca2+, cADPR and S1P. Their main targets are protein kinases as PKA and PKG, being then involved in phosphorylation mediated responses.[4] 2. Hydrophobic/membrane-associated – are insoluble in water and membrane-associated, being localized at intermembrane spaces, where they can bind to membrane-associated effector proteins. Examples: PIP3, DAG, phosphatidic acid, arachidonic acid and ceramide. They are involved in regulation of kinases and phosphatases, G protein associated factors and transcriptional factors.[4] 3. Gaseous – can be widespread through cell membrane and cytosol, including nitric oxide and carbon monoxide. Both of them can activate cGMP and, besides of being capable of mediating independent activities, they also can operate in a coordinated mode.[4] +-----+ https://link.springer.com/referenceworkentry/10.1007/978-1-0716-1006-0_769#citeas Blackwell, K.T. 12Jun2022 Biochemical Signaling Pathways and Diffusion: Overview. In: Jaeger, D., Jung, R. (eds) Encyclopedia of Computational Neuroscience. Springer, New York, NY. https://doi.org/10.1007/978-1-0716-1006-0_769 Print ISBN 978-1-0716-1004-6 Online ISBN 978-1-0716-1006-0 Signaling pathways modulate the function of neurons and neuronal networks through diverse processes. The most well-known function of signaling pathways is synaptic plasticity, which controls neuronal networks via modulation of the strength of synaptic connections. Signaling pathways also are critical for neuronal development, axon guidance, and regulation of transcription and translation. Signaling pathways are activated by the G protein-coupled transmembrane receptors, such as metabotropic glutamate receptors or noradrenergic receptors; by the receptor tyrosine kinases; and by calcium influx through NMDA receptors or voltage-dependent calcium channels. +-----+ https://medicine.umich.edu/dept/biochem/research/biochemical-signaling Biochemical Signaling The research of faculty in the Biochemical Signaling area probes the molecular mechanisms accounting for changes in cell metabolism that mediate the physiological adaptation of living cells in response to alterations in their environment. Often these cellular responses involve sequential biochemical reactions that form signaling cascades to coordinately regulate multiple cell functions. Some of the biochemical mechanisms studied in these signaling cascades include post-translational modifications of proteins such as phosphorylation, methylation, lipidation, and ubiquitination. Other mechanisms involve allosteric regulation of molecular function, including protein-protein and protein-DNA interactions. The goal of all of these studies is to understand the principles of coordinated molecular regulation at a biochemical level and to demonstrate the importance of these biochemical regulatory mechanisms in a cellular context. Home About Us Research Biochemical Signaling Macromolecular Structure and Mechanism Protein Processing and Folding Regulation of Gene Expression All Research Areas Education People News Events Career Development /home/bill/web/Neural nets/MindCode/images/UMich: Weidmann lab transcriptome-proteome interaction networks that underlie cellular transformations.jpg The Weidmann lab seeks to illuminate transcriptome-proteome interaction networks that underlie cellular transformations, particularly networks that promote cancer metastasis. /home/bill/web/Neural nets/MindCode/images/UMich: Vojtek lab roles of prenyl-binding proteins in trafficking and membrane localization of KRAS4b.jpg The Vojtek lab explores the roles of prenyl-binding proteins in trafficking and membrane localization of KRAS4b. /home/bill/web/Neural nets/MindCode/images/UMich: Seasholtz lab Corticotropin-Releasing Hormone Binding-Protein (CRH-BP) in the mammalian stress response.jpg Potential roles for Corticotropin-Releasing Hormone Binding-Protein (CRH-BP) in the mammalian stress response are under investigation in the Seasholtz lab. /home/bill/web/Neural nets/MindCode/images/UMich: Goldman lab signaling pathways that drive central nervous system regeneration (eg retina).jpg The Goldman lab studies signaling pathways that drive central nervous system regeneration using the retina as a model system. +-----+ https://medicine.umich.edu/dept/biochem/research/regulation-gene-expression Regulation of Gene Expression The control of gene expression is regulated in a highly organized fashion to ensure specific genes are expressed at the appropriate times and levels in response to various genetic and environmental stimuli. In eukaryotes, gene expression is controlled at multiple levels from transcription factor-mediated recruitment of the basal transcription machinery at specific gene promoters to processing and maturation of the RNA transcript. Disruption of these events in humans contributes to many pathologies including cancer, metabolic syndromes, and developmental disorders. Faculty who are investigating the regulation of gene expression are interested in numerous topics including transcriptional regulatory pathways in pro- and eukaryotes, DNA and RNA interactions with proteins, RNA processing and the functions of catalytic RNA, chromatin modification and remodeling, and three-dimensional organization of genes in the nucleus. Research employs a variety of model organisms and utilizes an array of modern techniques in biochemistry and molecular, cellular, and structural biology to elucidate the mechanisms that govern gene expression in pro- and eukaryotes. /home/bill/web/Neural nets/MindCode/images/UMich geneReg: Yan Zhang [biology, mechanism, techApp]s of bacterial CRISPR-Cas systems.jpg Researchers in Yan Zhang's lab explore the biology, mechanisms, and technological applications of bacterial CRISPR-Cas systems. /home/bill/web/Neural nets/MindCode/images/UMich geneReg: Uhler lab uses human stem cells, gene expression of FGF signaling components in Major Depressive Disorder (MDD).jpg The Uhler lab uses human stem cells to study how gene expression of FGF signaling components is altered in Major Depressive Disorder (MDD). /home/bill/web/Neural nets/MindCode/images/UMich geneReg: Freddolino lab how the transcription of genes is regulated by factors such as chromosomal location.jpg The Freddolino lab is interested in how the transcription of genes is regulated by factors such as chromosomal location. +-----+ https://www.cambridge.org/core/books/abs/chemical-biophysics/biochemical-signaling-modules/A3C97596D817FA2B215DEBE8D7F88835 5 - Biochemical signaling modules Published online by Cambridge University Press: 05Jun2012 Daniel A. Beard, Hong Qian Summary Overview The central dogma of molecular biology describes how one form of biological information (an organism's genetic sequence) is processed in terms of DNA replication, RNA transcription, and protein synthesis. However, a related mystery is yet to be worked out in sufficient detail: how is the information encoded in the DNA (i.e., genotypes) related to cellular functions (i.e., phenotypes)? How do different signals tell different cells to synthesize different proteins? To tackle these questions we adopt a view of the cell as a machine that processes diverse information. The hardware for cellular information processing consists of specialized biochemical reactions and their associated molecules, forming so-called signal transduction networks. As we have discussed in the previous chapter, the majority of biochemical reactions involve proteins acting as enzymatic catalysts. Reactions in signaling systems are no exception. In fact it is a common motif in signaling systems for enzymes to carry information via regulations of their biochemical activities; activities are modulated by covalent modification or allosteric binding by effector molecules. A central question in cellular biology is now to elucidate (meaning to develop models with reliable predictive power) the mechanisms by which the cells transducer information and perform their functions. Cellular biochemical signaling systems are customarily visualized as “logic circuits”; the components for the circuitry, now popularly called “modules”, consist of molecules and biochemical reactions. >> 63$ - BUY THIS BOOK!! +-----+ https://arxiv.org/abs/2301.03907 [Submitted on 10 Jan 2023 (v1), last revised 21 Apr 2023 (this version, v2)] Dynamical information synergy in biochemical signaling networks Lauritz Hahn, Aleksandra M. Walczak, Thierry Mora Biological cells encode information about their environment through biochemical signaling networks that control their internal state and response. This information is often encoded in the dynamical patterns of the signaling molecules, rather than just their instantaneous concentrations. Here, we analytically calculate the information contained in these dynamics for a number of paradigmatic cases in the linear regime, for both static and time-dependent input signals. When considering oscillatory output dynamics, we report the emergence of synergy between successive measurements, meaning that the joint information in two measurements exceeds the sum of the individual information. We extend our analysis numerically beyond the scope of linear input encoding to reveal synergetic effects in the cases of frequency or damping modulation, both of which are relevant to classical biochemical signaling systems. Subjects: Molecular Networks (q-bio.MN) Cite as: arXiv:2301.03907 [q-bio.MN] (or arXiv:2301.03907v2 [q-bio.MN] for this version) https://doi.org/10.48550/arXiv.2301.03907 Submission history From: Thierry Mora [view email] [v1] Tue, 10 Jan 2023 11:08:40 UTC (158 KB) [v2] Fri, 21 Apr 2023 10:47:52 UTC (169 KB) Lauritz Hahn, Aleksandra M. Walczak, Thierry Mora 10Jan2023 Dynamical information synergy in biochemical signaling networks, version2 21Apr2023 https://arxiv.org/abs/2301.03907 /home/bill/web/References/Neural Nets/MindCode/Hahn, Walczak, Mora 10Jan2023 Dynamical information synergy in biochemical signaling networks.pdf +-----+ https://pubmed.ncbi.nlm.nih.gov/32569947/ Curr Opin Cell Biol 2020 Oct:66:59-68. doi: 10.1016/j.ceb.2020.05.004. Epub 2020 Jun 20. Forced to communicate: Integration of mechanical and biochemical signaling in morphogenesis Abigail Kindberg 1 , Jimmy K Hu 2 , Jeffrey O Bush 3 Abigail Kindberg, Jimmy K Hu, Jeffrey O Bush 20Jun2020 Forced to communicate: Integration of mechanical and biochemical signaling in morphogenesis, Curr Opin Cell Biol, 2020 Oct:66:59-68 https://pubmed.ncbi.nlm.nih.gov/32569947/ /home/bill/web/Neural nets/MindCode/images/Kindberg, Hu, Bush 20Jun2020 Fig 1 mechanisms of mechanosensation.jpg /home/bill/web/Neural nets/MindCode/images/Kindberg, Hu, Bush 20Jun2020 Fig 2 integration of mechanical and biochemical.jpg /home/bill/web/Neural nets/MindCode/images/Kindberg, Hu, Bush 20Jun2020 Fig 3 mechanical modulation of chemical signaling.jpg Abstract Morphogenesis is a physical process that requires the generation of mechanical forces to achieve dynamic changes in cell position, tissue shape, and size as well as biochemical signals to coordinate these events. Mechanical forces are also used by the embryo to transmit detailed information across space and detected by target cells, leading to downstream changes in cellular properties and behaviors. Indeed, forces provide signaling information of complementary quality that can both synergize and diversify the functional outputs of biochemical signaling. Here, we discuss recent findings that reveal how mechanical signaling and biochemical signaling are integrated during morphogenesis and the possible context-specific advantages conferred by the interactions between these signaling mechanisms. Keywords: Actomyosin; Development; Eph; Ephrin; Force; Morphogenesis; PIEZO; Signaling; Taz; Tension; Yap. Introduction: force generation and detection in morphogenesis Morphogenesis occurs across a range of timescales and physical space, requiring the coordinated interplay of a host of different cell behaviors. Although ligand-based biochemical signaling elicits cellular responses during tissue morphogenesis, the mechanical forces generated by cells downstream of this signaling ultimately mold tissues. However, these forces can also be detected by cells, leading to biochemical and mechanical signal propagation within and between cells, which not only Mechanical signals coordinate physical information with cellular differentiation and proliferation Several recent articles have demonstrated that forces can signal to couple cell position within a tissue with cell fate specification, thereby coordinating physical information and cellular differentiation (Figure 2a). Although it is known that the stemness of epidermal progenitors can be manipulated by altering cell shape or ECM stiffness [23,24], how mechanical changes are used to enable specific cell fate decisions has remained unclear. Totaro et al. [25] recently demonstrated that cell Chemical signals modulate cell polarity, adhesion, and tissue deformability to signal mechanically The emergence of coordinated collective cell behaviors requires the detection, coupling, and propagation of forces across groups of cells. Tissue rheology, or the way in which tissues mechanically react, arises from the contractility of the cells composing the tissue, the ECM, and the strength of the cell–cell contacts within a tissue. Viscoelasticity determines the deformability of the tissue and permissibility for cellular arrangement in response to inductive signals. Modulation of these Mechanical modulation of chemical signaling by cell density and crowding forces As morphogenesis progresses, changes in tissue shape and cell organization can concurrently reshape the spatial distribution of signaling molecules (Figure 3a). For instance, villus formation in the developing chick gut as a result of mechanical buckling of the endodermal epithelium distorts the SHH signaling gradient from the epithelium, concentrating the signal at the tip of each villus to activate high-threshold response genes in the mesenchyme that ultimately determine the location of Mechanical force as a long-range intermediary signal to regulate morphogenesis While paracrine signaling is only effective over a relatively short distance of 50–100 μm (spanning 5–10 cells) owing to rapid signal dilution and decay in its intensity [55, 56, 57], mechanical forces can be directionally transmitted over a longer distance and function as a long-range morphogenetic signal downstream of a localized biochemical stimulus (Figure 3b). One example demonstrating mechanical signaling over distance is the regulation of zebrafish body elongation by the tail organizer [ Conclusions and perspectives Cells may have evolved to actively use force as an extracellular second messenger to transduce information between cells with several advantages. The recent studies that we describe above here give insight into this idea and present explanations of the advantages that might be achieved by using mechanical signals: these signals can coordinate growth of organs, specify cell fate with respect to tissue architecture, modulate chemical signals, and act over longer distances than biochemical +-----+ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813785/ Science. Author manuscript; available in PMC 2016 Mar 30. Published in final edited form as: Science. 2014 Dec 12; 346(6215): 1370–1373. doi: 10.1126/science.1254933 PMCID: PMC4813785 NIHMSID: NIHMS768788 PMID: 25504722 Accurate Information Transmission Through Dynamic Biochemical Signaling Networks Jangir Selimkhanov,1,* Brooks Taylor,1,* Jason Yao,2 Anna Pilko,2 John Albeck,3 Alexander Hoffmann,4,5 Lev Tsimring,4,6 and Roy Wollman2,4,7,+ Abstract Stochasticity inherent to biochemical reactions (intrinsic noise) and variability in cellular states (extrinsic noise) degrade information transmitted through signaling networks. We analyze the ability of temporal signal modulation, that is dynamics, to reduce noise-induced information loss. In the extracellular signal-regulated kinase (ERK), calcium (Ca2+), and nuclear factor kappa-B (NFκB) pathways, response dynamics resulted in significantly greater information transmission capacities compared to non-dynamic responses. Theoretical analysis demonstrated that signaling dynamics has a key role in overcoming extrinsic noise. Experimental measurements of information transmission in the ERK network under varying signal-to-noise confirmed our predictions and showed that signaling dynamics mitigate, and can potentially eliminate, extrinsic noise induced information loss. By curbing the information-degrading effects of cell-to-cell variability, dynamic responses substantially increase the accuracy of biochemical signaling networks. +-----+ https://www.khanacademy.org/science/ap-biology/cell-communication-and-cell-cycle/cell-communication/a/introduction-to-cell-signaling Forms of signaling Cell-cell signaling involves the transmission of a signal from a sending cell to a receiving cell. However, not all sending and receiving cells are next-door neighbors, nor do all cell pairs exchange signals in the same way. There are four basic categories of chemical signaling found in multicellular organisms: paracrine signaling, autocrine signaling, endocrine signaling, and signaling by direct contact. The main difference between the different categories of signaling is the distance that the signal travels through the organism to reach the target cell. Paracrine signaling Often, cells that are near one another communicate through the release of chemical messengers (ligands that can diffuse through the space between the cells). This type of signaling, in which cells communicate over relatively short distances, is known as paracrine signaling. Paracrine signaling allows cells to locally coordinate activities with their neighbors. Although they're used in many different tissues and contexts, paracrine signals are especially important during development, when they allow one group of cells to tell a neighboring group of cells what cellular identity to take on. [Example: spinal cord development] Synaptic signaling One unique example of paracrine signaling is synaptic signaling, in which nerve cells transmit signals. This process is named for the synapse, the junction between two nerve cells where signal transmission occurs. When the sending neuron fires, an electrical impulse moves rapidly through the cell, traveling down a long, fiber-like extension called an axon. When the impulse reaches the synapse, it triggers the release of ligands called neurotransmitters, which quickly cross the small gap between the nerve cells. When the neurotransmitters arrive at the receiving cell, they bind to receptors and cause a chemical change inside of the cell (often, opening ion channels and changing the electrical potential across the membrane). Synaptic signaling. Neurotransmitter is released from vesicles at the end of the axon of the sending cell. It diffuses across the small gap between sending and target neurons and binds to receptors on the target neuron. Synaptic signaling. Neurotransmitter is released from vesicles at the end of the axon of the sending cell. It diffuses across the small gap between sending and target neurons and binds to receptors on the target neuron. Image modified from "Signaling molecules and cellular receptors: Figure 2," by OpenStax College, Biology (CC BY 3.0). The neurotransmitters that are released into the chemical synapse are quickly degraded or taken back up by the sending cell. This "resets" the system so they synapse is prepared to respond quickly to the next signal. Paracrine signaling: a cell targets a nearby cell (one not attached by gap junctions). The image shows a signaling molecule produced by one cell diffusing a short distance to a neighboring cell. Autocrine signaling: a cell targets itself, releasing a signal that can bind to receptors on its own surface. Autocrine signaling In autocrine signaling, a cell signals to itself, releasing a ligand that binds to receptors on its own surface (or, depending on the type of signal, to receptors inside of the cell). This may seem like an odd thing for a cell to do, but autocrine signaling plays an important role in many processes. Image modified from "Signaling molecules and cellular receptors: Figure 1," by OpenStax College, Biology (CC BY 3.0). For instance, autocrine signaling is important during development, helping cells take on and reinforce their correct identities. From a medical standpoint, autocrine signaling is important in cancer and is thought to play a key role in metastasis (the spread of cancer from its original site to other parts of the body). In many cases, a signal may have both autocrine and paracrine effects, binding to the sending cell as well as other similar cells in the area. Endocrine signaling When cells need to transmit signals over long distances, they often use the circulatory system as a distribution network for the messages they send. In long-distance endocrine signaling, signals are produced by specialized cells and released into the bloodstream, which carries them to target cells in distant parts of the body. Signals that are produced in one part of the body and travel through the circulation to reach far-away targets are known as hormones. In humans, endocrine glands that release hormones include the thyroid, the hypothalamus, and the pituitary, as well as the gonads (testes and ovaries) and the pancreas. Each endocrine gland releases one or more types of hormones, many of which are master regulators of development and physiology. For example, the pituitary releases growth hormone (GH), which promotes growth, particularly of the skeleton and cartilage. Like most hormones, GH affects many different types of cells throughout the body. However, cartilage cells provide one example of how GH functions: it binds to receptors on the surface of these cells and encourages them to divide ‍ Endocrine signaling: a cell targets a distant cell through the bloodstream. A signaling molecule is released by one cell, then travels through the bloodstream to bind to receptors on a distant target cell elsewhere in the body. Image modified from "Signaling molecules and cellular receptors: Figure 2," by OpenStax College, Biology (CC BY 3.0). [Do plants have endocrine signaling?] Signaling through cell-cell contact Gap junctions in animals and plasmodesmata in plants are tiny channels that directly connect neighboring cells. These water-filled channels allow small signaling molecules, called intracellular mediators, to diffuse between the two cells. Small molecules and ions are able to move between cells, but large molecules like proteins and DNA cannot fit through the channels without special assistance. The transfer of signaling molecules transmits the current state of one cell to its neighbor. This allows a group of cells to coordinate their response to a signal that only one of them may have received. In plants, there are plasmodesmata between almost all cells, making the entire plant into one giant network. Signaling across gap junctions. A cell targets a neighboring cell connected via gap junctions. Signals travel from one cell to the other by passing through the gap junctions. Signaling across gap junctions. A cell targets a neighboring cell connected via gap junctions. Signals travel from one cell to the other by passing through the gap junctions. Image modified from "Signaling molecules and cellular receptors: Figure 1," by OpenStax College, Biology (CC BY 3.0). In another form of direct signaling, two cells may bind to one another because they carry complementary proteins on their surfaces. When the proteins bind to one another, this interaction changes the shape of one or both proteins, transmitting a signal. This kind of signaling is especially important in the immune system, where immune cells use cell-surface markers to recognize “self” cells (the body's own cells) and cells infected by pathogens. A diagram of two cells with the caption a natural killer, NK, immune cell recognizes a healthy cell of the body by binding to a “self” marker on the cell’s surface. The cell on the left is labeled NK cell and it has a small structure with a circular end extending from the cell membrane. The circular end of the small structure is joined to a receptor on the cell membrane of the cell on the right. The cell on the right is labeled healthy cell. A diagram of two cells with the caption a natural killer, NK, immune cell recognizes a healthy cell of the body by binding to a “self” marker on the cell’s surface. The cell on the left is labeled NK cell and it has a small structure with a circular end extending from the cell membrane. The circular end of the small structure is joined to a receptor on the cell membrane of the cell on the right. The cell on the right is labeled healthy cell. _Image modified from "Adaptive immune response: Figure 7," by OpenStax College, Biology (CC BY 3.0)._ +-----+ https://biologydictionary.net/types-and-stages-of-cell-signaling/ Types and Stages of Cell Signaling BD Editors, Last Updated: April 17, 2019 /home/bill/web/Neural nets/MindCode/images/biologydictionary: variety of cell signaling pathways within a single cell.jpg Types of Cell Signaling There are 5 main types of cell signaling which are mainly classified by how far the signals must travel, and the ultimate proximity of the cells sending and receiving the cells. Intracrine signals stay within a single cell, but are used by the cell to coordinate and control the many biochemical reactions taking place at any given moment. Autocrine signals are released by a cell, but are still intended to take action on the cell itself. These signals can also travel short distances outside of the target cell and affect near-by cells. Immune cells commonly secrete autocrine signals. Juxtacrine signals are sent from one cell to a neighboring cell that it is physically touching. Typically, these signals are transmitted through some of the same proteins and molecules which hold the cells together, which insures that a bonded tissue will produce a cohesive reaction. Paracrine signals are sent from one cell to another cell in its immediate proximity. A great example of paracrine signaling is found in the nerve cells. When a nervous signal is to be passed from one cell to another, the sending cell released neurotransmitter molecules, which act as a signal for the second cell to initiate and transmit a signal. These signals only travel short distances. Endocrine signals are sent very long distances, often by the tissues in your body that secrete hormones. Hormones are able to circulate through the blood, affecting many different cell types throughout the body to create a unified response. The following image shows a wide variety of cell signaling pathways within a single cell, and the many different biochemical reactions they stimulate. +-----+ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370337/ Bioelectricity. September 2020; 2(3): 210–220. Published online 2020 Sep 16. doi: 10.1089/bioe.2020.0001 PMCID: PMC8370337 PMID: 34476353 Integrating Bioelectrical Currents and Ca2+ Signaling with Biochemical Signaling in Development and Pathogenesis Ang Li, PhD, 1 Jingsong Zhou, MD, PhD, 1 Randall B. Widelitz, PhD, 2 Robert H. Chow, MD, PhD, 3 and Cheng-Ming Chuong, MD, PhD 2 Abstract Roles of bioelectrical signals are increasingly recognized in excitable and nonexcitable non-neural tissues. Diverse ion-selective channels, pumps, and gap junctions participate in bioelectrical signaling, including those transporting calcium ions (Ca2+). Ca2+ is the most versatile transported ion, because it serves as an electrical charge carrier and a biochemical regulator for multiple molecular binding, enzyme, and transcription activities. We aspire to learn how bioelectrical signals crosstalk to biochemical/biomechanical signals. In this study, we review four recent studies showing how bioelectrical currents and Ca2+ signaling affect collective dermal cell migration during feather bud elongation, affect chondrogenic differentiation in limb development, couple with mechanical tension in aligning gut smooth muscle, and affect mitochondrial function and skeletal muscle atrophy. We observe bioelectrical signals involved in several developmental and pathological conditions in chickens and mice at multiple spatial scales: cellular, cellular collective, and subcellular. These examples inspire novel concept and approaches for future basic and translational studies. Keywords: collective cell migration, chondrogenic differentiation, smooth muscle alignment, neuromuscular degenerative disease #08********08 #] 13Dec2023 [m,t]RNA: construct peptide sequence, protein see "$d_web"'Neural nets/MindCode/MindCode webPage.html' "$d_web"'/Neural nets/MindCode/images/wikipedia: [m,t]RNA [peptide, protein] synthesis.png' 14Dec2023 double-mRNA strand coprocessing : "$d_web"'/Neural nets/MindCode/images/' wikipedia: [m,t]RNA [peptide, protein] synthesis.xcf wikipedia: [m,t]RNA [peptide, protein] synthesis.png width: 669px, hi: 414px 17Dec2023 [side-by-side-in depth, 2-strand] ribosomes 4*4 = 16 combinations #08********08 #] 21Nov2023 search "ribosomes in cells" +-----+ https://www.britannica.com/science/ribosome ribosome, particle that is present in large numbers in all living cells and serves as the site of protein synthesis. Ribosomes occur both as free particles in prokaryotic and eukaryotic cells and as particles attached to the membranes of the endoplasmic reticulum in eukaryotic cells. The small particles that came to be known as ribosomes were first described in 1955 by Romanian-born American cell biologist George E. Palade, who found them to be frequently associated with the rough endoplasmic reticulum of eukaryotic cells. protein synthesis protein synthesis DNA in the cell nucleus carries a genetic code, which consists of sequences of adenine (A), thymine (T), guanine (G), and cytosine (C) (Figure 1). RNA, which contains uracil (U) instead of thymine, carries the code to protein-making sites in the cell. To make RNA, DNA pairs its bases with those of the "free" nucleotides (Figure 2). Messenger RNA (mRNA) then travels to the ribosomes in the cell cytoplasm, where protein synthesis occurs (Figure 3). The base triplets of transfer RNA (tRNA) pair with those of mRNA and at the same time deposit their amino acids on the growing protein chain. Finally, the synthesized protein is released to perform its task in the cell or elsewhere in the body. Ribosomes are remarkably abundant in cells. A single actively replicating eukaryotic cell, for example, may contain as many as 10 million ribosomes. In the bacterium Escherichia coli (a prokaryote), ribosomes may number as many as 15,000, constituting as much as one-quarter of the cell’s total mass. The size of the ribosomes within cells varies, depending on the cell type and on factors such as whether the cell is resting or replicating. The average ribosome of E. coli, the best-characterized example, measures about 200 angstroms (about 20 nm) in diameter. Mechanism of cellular autophagy, illustration for Nobel Prize Award in Medicine 2016. 3D illustration showing fusion of lysosome with autophagosome containing microbes and molecules. Britannica Quiz Parts of a Cell Quiz Ribosomes are made up of ribosomal proteins and ribosomal RNA (rRNA). In prokaryotes, ribosomes are roughly 40 percent protein and 60 percent rRNA. In eukaryotes, ribosomes are about half protein and half rRNA. Ribosomes are usually made up of three or four rRNA molecules and anywhere from about 40 to 80 different ribosomal proteins. Each ribosome is composed of two subunits, a larger one and a smaller one, each of which has a characteristic shape. In eukaryotes, ribosomal subunits are formed in the nucleolus of the cell’s nucleus. The subunits typically are referred to in terms of their sedimentation rate, which is measured in Svedberg units (S), in a centrifugal field. The small and large subunits of eukaryotes are designated 40S and 60S, respectively, while prokaryotes contain a small 30S subunit and a large 50S subunit. Ribosomes are the sites at which information carried in the genetic code is converted into protein molecules. Ribosomal molecules of messenger RNA (mRNA) determine the order of transfer RNA (tRNA) molecules that are bound to nucleotide triplets (codons). The order of tRNA molecules ultimately determines the amino acid sequence of a protein. Molecules of rRNA catalyze the peptidyl transferase reaction, which forms peptide bonds between the amino acids, linking them together to form proteins. The newly formed proteins detach themselves from the ribosome site and migrate to other parts of the cell for use. /home/bill/web/Neural nets/MindCode/images/ britannica: endoplasmic reticulum.png britannica: how DNA directs protein synthesis.png #08********08 #] 21Nov2023 search "mRNA multi-strand co-processing", "co-processing of multi-mRNA sequences" >> Howell: I can find nothing to indicate co-processing of mRNA strands!? introns ?!???!!! "co-processing of multi-mRNA sequences" +-----+ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744312/ Coordinated control of rRNA processing by RNA polymerase I Catherine E. Scull and David A. Schneider Trends Genet. Author manuscript; available in PMC 2020 Oct 1. Published in final edited form as: Trends Genet. 2019 Oct; 35(10): 724–733. Published online 2019 Jul 26. doi: 10.1016/j.tig.2019.07.002 Abstract Ribosomal RNA (rRNA) is co-and post-transcriptionally processed into active ribosomes. This process is dynamically regulated by direct covalent modifications of the polymerase that synthesizes the rRNA, RNA polymerase I (Pol I), and by interactions with co-factors that influence initiation, elongation, and termination activities of Pol I. The rate of transcription elongation by Pol I directly influences processing of nascent rRNA, and changes in Pol I transcription rate result in alternative rRNA processing events that lead to cellular signaling alterations and stress. It is clear that in divergent species, there exists robust organization of nascent rRNA processing events during transcription elongation. This review evaluates the current state of our understanding of the complex relationship between transcription elongation and rRNA processing. +-----+ https://pubmed.ncbi.nlm.nih.gov/27103888/ Genomics Inform . 2016 Mar;14(1):29-33. doi: 10.5808/GI.2016.14.1.29. Epub 2016 Mar 31. Compiling Multicopy Single-Stranded DNA Sequences from Bacterial Genome Sequences Wonseok Yoo 1 , Dongbin Lim 1 , Sangsoo Kim 1 PMID: 27103888 PMCID: PMC4838527 DOI: 10.5808/GI.2016.14.1.29 Abstract A retron is a bacterial retroelement that encodes an RNA gene and a reverse transcriptase (RT). The former, once transcribed, works as a template primer for reverse transcription by the latter. The resulting DNA is covalently linked to the upstream part of the RNA; this chimera is called multicopy single-stranded DNA (msDNA), which is extrachromosomal DNA found in many bacterial species. Based on the conserved features in the eight known msDNA sequences, we developed a detection method and applied it to scan National Center for Biotechnology Information (NCBI) RefSeq bacterial genome sequences. Among 16,844 bacterial sequences possessing a retron-type RT domain, we identified 48 unique types of msDNA. Currently, the biological role of msDNA is not well understood. Our work will be a useful tool in studying the distribution, evolution, and physiological role of msDNA. +-----+ #] 21Nov2023 Gu, Su, Huang: Simultaneous expansions of microRNAs and protein-coding genes https://pubmed.ncbi.nlm.nih.gov/19214983/ J Exp Zool B Mol Dev Evol 2009 May 15;312B(3):164-70. doi: 10.1002/jez.b.21273. Simultaneous expansions of microRNAs and protein-coding genes by gene/genome duplications in early vertebrates Xun Gu 1 , Zhixi Su, Yong Huang PMID: 19214983 DOI: 10.1002/jez.b.21273 Abstract Does miRNAs underlie the origin of organismal complexity in vertebrates? The current controversy is focused on whether the inventory of vertebrate miRNAs can be explained by the classical two-round genome duplications. We estimate the age distribution of vertebrate miRNA duplication events, showing the evolutionary scenario that gene/genome duplications in the early stage of vertebrates may expand the protein-encoding genes and miRNAs simultaneously. We further speculate that genetically lying behind the evolution of vertebrate complexity may be the proteome doubling and alterations of the epigenetic (including miRNA) machinery. +-----+ https://openstax.org/books/biology-ap-courses/pages/15-4-rna-processing-in-eukaryotes 15.4 RNA Processing in Eukaryotes Evolution Connection RNA Editing in Trypanosomes The trypanosomes are a group of protozoa that include the pathogen Trypanosoma brucei, which causes sleeping sickness in humans (Figure 15.13). Trypanosomes, and virtually all other eukaryotes, have organelles called mitochondria that supply the cell with chemical energy. Mitochondria are organelles that express their own DNA and are believed to be the remnants of a symbiotic relationship between a eukaryote and an engulfed prokaryote. The mitochondrial DNA of trypanosomes exhibit an interesting exception to The Central Dogma: their pre-mRNAs do not have the correct information to specify a functional protein. Usually, this is because the mRNA is missing several U nucleotides. The cell performs an additional RNA processing step called RNA editing to remedy this. Micrograph shows T. brucei, which has a u-shaped cell body and a long tail. Figure 15.13 Trypanosoma brucei is the causative agent of sleeping sickness in humans. The mRNAs of this pathogen must be modified by the addition of nucleotides before protein synthesis can occur. (credit: modification of work by Torsten Ochsenreiter) Other genes in the mitochondrial genome encode 40- to 80-nucleotide guide RNAs. One or more of these molecules interacts by complementary base pairing with some of the nucleotides in the pre-mRNA transcript. However, the guide RNA has more A nucleotides than the pre-mRNA has U nucleotides to bind with. In these regions, the guide RNA loops out. The 3' ends of guide RNAs have a long poly-U tail, and these U bases are inserted in regions of the pre-mRNA transcript at which the guide RNAs are looped. This process is entirely mediated by RNA molecules. That is, guide RNAs—rather than proteins—serve as the catalysts in RNA editing. RNA editing is not just a phenomenon of trypanosomes. In the mitochondria of some plants, almost all pre-mRNAs are edited. RNA editing has also been identified in mammals such as rats, rabbits, and even humans. What could be the evolutionary reason for this additional step in pre-mRNA processing? One possibility is that the mitochondria, being remnants of ancient prokaryotes, have an equally ancient RNA-based method for regulating gene expression. In support of this hypothesis, edits made to pre-mRNAs differ depending on cellular conditions. Although speculative, the process of RNA editing may be a holdover from a primordial time when RNA molecules, instead of proteins, were responsible for catalyzing reactions. Refer to RNA Editing in Trypanosomes In eukaryotes, pre-mRNAs are processed to form mature mRNAs. How does the mRNA editing that occurs in Trypanosoma brucei differ from mRNA processing that occurs in all eukaryotes? mRNA editing changes the coding sequence of the mRNA, but mRNA processing does not. mRNA editing splices out noncoding RNA, but mRNA processing does not. mRNA editing adds a cap of 5’-methylguanosine to the mRNA, but mRNA processing does not. mRNA editing adds a 3’ poly-A tail, but mRNA processing does not. #] Pre-mRNA Splicing, introns Eukaryotic genes are composed of exons, which correspond to protein-coding sequences (ex-on signifies that they are expressed), and intervening sequences called introns (int-ron denotes their intervening role), which may be involved in gene regulation but are removed from the pre-mRNA during processing. Intron sequences in mRNA do not encode functional proteins. The discovery of introns came as a surprise to researchers in the 1970s who expected that pre-mRNAs would specify protein sequences without further processing, as they had observed in prokaryotes. The genes of higher eukaryotes very often contain one or more introns. These regions may correspond to regulatory sequences; however, the biological significance of having many introns or having very long introns in a gene is unclear. It is possible that introns slow down gene expression because it takes longer to transcribe pre-mRNAs with lots of introns. Alternatively, introns may be nonfunctional sequence remnants left over from the fusion of ancient genes throughout evolution. This is supported by the fact that separate exons often encode separate protein subunits or domains. For the most part, the sequences of introns can be mutated without ultimately affecting the protein product. All of a pre-mRNA’s introns must be completely and precisely removed before protein synthesis. If the process errs by even a single nucleotide, the reading frame of the rejoined exons would shift, and the resulting protein would be dysfunctional. The process of removing introns and reconnecting exons is called splicing (Figure 15.14). Introns are removed and degraded while the pre-mRNA is still in the nucleus. Splicing occurs by a sequence-specific mechanism that ensures introns will be removed and exons rejoined with the accuracy and precision of a single nucleotide. The splicing of pre-mRNAs is conducted by complexes of proteins and RNA molecules called spliceosomes. +----------+ "mRNA multi-strand co-processing" +-----+ https://link.springer.com/referenceworkentry/10.1007/978-1-4614-6436-5_41-4 Marvin, B., Inada, M. 01Jan2014 Co-transcriptional mRNA Processing in Eukaryotes. In: Bell, E. (eds) Molecular Life Sciences. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6436-5_41-4 Synopsis Gene expression describes the flow of genetically encoded information from DNA to its intermediary form, mRNA, and its functional form, protein. In eukaryotes, mRNAs are co-transcriptionally highly processed from a precursor mRNA or pre-mRNA to a mature mRNA. To form mature mRNAs, the pre-mRNA’s 5′ end is capped, its coding regions are joined together during a process called pre-mRNA splicing, and its 3′ end is cleaved and appended with a poly(A) tail. By modifying pre-mRNAs, the cell is afforded multiple opportunities for regulatory control in the diversity and levels of an mRNA prior to its translation into protein. +-----+ https://bio.libretexts.org/Bookshelves/Biochemistry/Fundamentals_of_Biochemistry_(Jakubowski_and_Flatt)/03%3A_Unit_III-_Information_Pathway/25%3A_RNA_Metabolism/25.02%3A_RNA_Processing Henry Jakubowski and Patricia Flatt College of St. Benedict/St. John's University and Western Oregon University Post-transcriptional modifications of rRNA and tRNA will be topics of Chapter 27 as their structure and function in protein synthesis will be a focal point. Thus, this section will focus on post-transcriptional modifications of mRNA. We'll spend most of our time on eukaryotic RNA processing. #08********08 #] 10Nov2023 cat digiVoice, file-away d_voice="$d_web"'Neural nets/Mind2023/voice musings/' cat "$d_voice"'231110_0916 same code, diff [mechnsm, pgm, protein] 1.mp3' "$d_voice"'231110_0917 same code, diff [mechnsm, pgm, protein] 2 subroutines.mp3' "$d_voice"'231110_1339 same code, diff [mechnsm, pgm, protein] 3.mp3' "$d_voice"'231110_1343 same code, diff [mechnsm, pgm, protein] 4 [stat, NN] inference.mp3' "$d_voice"'231110_1427 same code, diff [pgm, protein] - analogy of local symbols in programming.mp3' >"$d_voice"'231110_0916 same code, diff [mechnsm, pgm, protein].mp3' >> works #08********08 #] 08Nov2023 emrep Juyang Weng note used : Examples at present : some of the DNA (ergo RNA) isn't for protein synthesis, it is "program code" proteins themselves can probably do much, but it seems that direct use of mRNA information would be much more [fast, robust, flexible] (base 4 for a single OR[acid, base], 3*4 bits for one strand of 2 for codons of 3 acid-base pairs) 5' start sequences can act like addresses in computer programs #08********08 #] 08Nov2023 emrep Juyang Weng - link didn't work The link that I sent won't work, as I had "doubled" the "http://". full form : http://www.billhowell.ca/Neural%20nets/Mind2023/Mind2023%20webPage.html
try again insert link : Mind2023 webPage.html
html insert : Mind2023 webPage.html

The "html insert" form is what I should use for emails, because when I get lazy the use of shortcuts often cause problems. If all esle faiils, copy the "full form" to a text processor, change the %20 to a space, copy-paste the full URL to your browser. The next problem may be that I'm just about to update all my website pages while I am changing my website management software slightly... Bill Howell http://www.billhowell.ca/Neural%20nets/Mind2023/Mind2023%20webPage.html http://http//www.billhowell.ca/Neural%20nets/Mind2023/Mind2023%20webPage.html #08********08 #] 08Nov2023 add [Proteomic, Neuroinformatic]s * [voice, section] done very superficially upload again! see "Setup, ToDos" above #08********08 #] 07Nov2023 search "Corona virus mRNA vaccine and Shapiro and Benenson" >> nothing #08********08 #] 07Nov2023 search "Corona virus mRNA vaccine and Israeli scientists" +-----+ https://www.i24news.tv/en/news/israel/1624352672-israeli-scientists-at-forefront-of-mrna-vaccination-revolution Israeli scientists at forefront of mRNA vaccination revolution David Brummer June 22, 2021 at 05:09 AM phto: Immunologist Prof David Naor of the Hebrew University of Jerusalem stands in his office on January 18, The development of these therapeutic vaccines can help in the treatment of autoimmune diseases and cancer In the past year or so, mRNA vaccines have become headline news as their development has been key to the successful roll-out in many countries of an immunization program to combat the COVID-19 pandemic. What might be less well-known, however, is that an Israeli immunology researcher affiliated with the Lautenberg Center in the Medicine Faculty at the Hebrew University of Jerusalem (HUJI) completed a series of research experiments more than a decade ago that showed the potential for mRNA therapeutics in autoimmune and cancer diseases. “I read that CNN reported that US scientists suggested to extrapolate mRNA vaccines technology of COVID-19 for use in auto-immune diseases and cancers,” said Prof David Naor, the immunologist in question. “I realized that I had already done this more than 10 years ago, performing research that showed the potential for mRNA vaccines to combat autoimmune diseases and cancers.” Practically, we used cDNA vaccines, which were the first generation of mRNA vaccines, and they were efficient in the therapy of animal models of autoimmune diseases and cancer. “We published our findings in scientific literature,” he explained. “We wanted to encourage mRNA vaccinations [we called it then “gene vaccination”] - and the technology used to make them - to be used against infections and other diseases.” “I used a technique of mRNA-like vaccines to test them against animal models of autoimmune diseases, such as Type I diabetes and Multiple Sclerosis as well as breast cancer. We experimented on mice - because it is easy to recapitulate the pathologies in these rodents by simple manipulations. Naor said that the technology showed that mRNA vaccines were able to ameliorate or even nearly cure the diseases under investigation. While the therapeutic use of mRNA vaccines is now a focus of world attention, Naor pointed out that his laboratory’s research paper was one of the first that showed that mRNA could be used to treat a range of diseases. The professor maintained that he and his colleagues did the work “accidentally.” “At the time, we were not aware that our research in animals could definitely be transferred to use in humans, but the COVID-19 mRNA vaccine is the first successful mass use of the technology and we showed that it may be able to be used for other diseases too.” He emphasized that the original experiments were crucial because they showed the many-faceted uses to which mRNA vaccinations could be put - and the range of autoimmune and cancer diseases they could treat. It was the potential benefit that seemed to excite him most, arguing that mRNA vaccines could help treat or cure diseases that kill in an order of magnitude greater than COVID-19. “We can’t yet do it for every disease with humans, but it works well in treating autoimmune diseases and cancer in animals and hopefully, in human beings in the future.” “The main challenge at the moment - and Moderna found this to an extent - is how to deliver RNA into body tissues. Using a vaccination is enough to penetrate a few cells in the muscles, which in the case of COVID-19 was sufficient.” Karni assessed that the current development of nanoparticles meant that a solution to this issue would likely be forthcoming in the next few years. He anticipated that many vaccines in the future will be based on RNA. “It is much faster and it was actually quite straightforward to design the sequence for COVID-19. It is relatively easy to make RNA and it is very tempting to use it for many diseases - and especially if there was a new virus or pandemic. +-----+ https://www.npr.org/sections/health-shots/2023/10/02/1202941256/nobel-prize-goes-to-scientists-who-made-mrna-covid-vaccines-possible Nobel Prize goes to scientists who made mRNA COVID vaccines possible Updated October 2, 20232:38 PM ET Heard on Morning Edition Scott Hensley, Rob Stein A biochemist born in Hungary and an American immunologist have won the 2023 Nobel Prize for Physiology or Medicine for research that led to the development of the two most important COVID-19 vaccines. Katalin Karikó and Drew Weissman met at copy machine at the University of Pennsylvania in Philadelphia and collaborated for decades to try to find ways to use genetic material called messenger RNA, or mRNA, to make vaccines. The scientists discovered that modifying a chemical building block of mRNA kept the immune system from destroying the material and enabled it to instead stimulate protection against viruses. They published a seminal paper describing their work in 2005. When the pandemic erupted, the vaccines developed by Moderna and Pfizer-BioNTech used the pair's techniques to create highly safe and effective vaccines in record time. ... The pair's discovery "fundamentally changed our understanding of how mRNA interacts with our immune system," the panel that awarded the prize said. In addition, the work "contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times." Speaking to reporters at the University of Pennsylvania Monday, Weissman, 64, said the pair had to overcome many obstacles. "We couldn't get funding. We couldn't get publications. We couldn't get people to notice RNA as something interesting. And pretty much everybody gave up on it," Weissman said. "But Kati (Karikó) lit the match and we spent the rest of our 20 plus years working together figuring out how to get it to work." Karikó, 68, had to overcome big challenges. For years, she went from one low-paying research job to another and even slept in her office at times. She says she was forced to retire from Penn and then commuted to work at BioNTech. But said she never gave up. And her mother never gave up hope she'd eventually win a Nobel. "My mom, who passed away two years ago at age 89, every fall she was listening and she said to me, 'You know, you might get this year.' And I said, 'Mom, I couldn't even get a grant,' " Karikó said in a 2020 interview with NPR. The first prize in the category was awarded in 1901. Of the 227 people whose work has been recognized with the prize, Karikó is only the 13th woman among them. +-----+ https://www.ynetnews.com/magazine/article/ByMFND12O Israeli scientists at forefront of mRNA vaccination revolution While crucial in the development of the first effective COVID-19 vaccines, Israeli immunology researcher Prof. David Naor's research found that mRNA could also help treat autoimmune diseases as well as cancer i24NEWS|06.22.21 | 08:32 same as above : https://www.i24news.tv/en/news/israel/1624352672-israeli-scientists-at-forefront-of-mrna-vaccination-revolution +-----+ https://www.ctvnews.ca/health/coronavirus/how-the-early-work-of-a-canadian-scientist-and-his-team-made-the-covid-19-vaccines-possible-1.5601481 How the early work of a Canadian scientist and his team made the COVID-19 vaccines possible How the mRNA vaccines produced by companies such as Moderna and Pfizer-BioNTech work is that the mRNA itself is wrapped in a protective shell made of lipid nanoparticles to allow it to enter the body and teach the immune system how to fight the novel coronavirus. Without this crucial delivery system provided by the lipid nanoparticles, called LNP, the vaccines would not work. Canadian scientist Ian MacLachlan has been watching the vaccine rollout with awe, knowing he and his team played a vital role in their development, which began decades ago. “There's a part of me that is almost overwhelmed, how effective and powerful these vaccines have been,” MacLachlan told CTV News in an interview. “There would be no mRNA vaccines without the LNP system that was developed right here in Canada.” MacLachlan was featured in a recent Forbes investigation,(opens in a new tab) which dove into the tangled web of scientific work, patents, companies and lawsuits that surround the issue of who deserves credit for LNP, and specifically, the LNP used in COVID-19 vaccines. A team of dedicated scientists in Vancouver were part of this. They knew that the world was going to need new tools for fighting diseases, and were determined to develop some. “We wrote the screenplay for this movie,” MacLachlan said. "We saw this coming. We know that there are these emerging infectious diseases that are out there. And we as a society need to prepare for them. And one of the ways that we can prepare for them is to develop these types of technologies and to make them as broadly available as possible, so that when that time comes, they're there for our societies to use.” In the early 2000s, scientists were honing in on the therapeutical potential of RNA. But for RNA-based drugs to work, they need to be delivered in a way that allows it to enter a cell. Over the coming decade, MacLachlan and a team at Protiva, a company he founded, worked on that problem, and came up with a way to safely deliver RNA. They found that a specific ratio of four lipids created the delivery system necessary to cover, protect RNA, and get it into the cell. Mark Kay, a professor of genetics at Stanford University, became aware of MacLachlan and his team’s work in the field when he was looking into siRNA, a therapeutical method that uses RNA to turn off certain genes. “It was clear from the work that he was doing that they had really made some extremely important discoveries that would allow for these RNAs to be delivered in a way that were therapeutic, as well as safe, and ultimately in humans,” Kay told CTV News. He explained that while other scientists were working in that field at the time, when it came to delivery systems that could be used safely in humans, MacLachlan and his team’s method stood out. “Clearly the innovation that went into these lipid nanoparticles […] I think is a game changer,” he said. #08********08 #] 07Nov2023 MindCode: online upload [addition, change]s "$d_PROJECTS"'bin - secure/lftp update entire webSite.sh' # onLine update dWebAll_upload_online pWebPageL_upload_online 14:50$ bash "$d_PROJECTS"'bin - secure/lftp update entire webSite.sh' dWebAll_upload_online... forgot to add webPage to pHtmlPathAll_L.txt >> I added it while all non-html being uploaded maybe it will upload "$d_web"'Neural nets/Mind2023/Mind2023 webPage.html' #08********08 #] 07Nov2023 split voice recording /home/bill/web/Neural nets/Mind2023/voice musings/231106_2212 Glenn Borchardts concept of infinity, avoid myopic thinking.mp3 00:00:00 231106_2212 Glenn Borchardts concept of infinity, avoid myopic thinking.mp3 00:01:22 231106_2212 plants, fungi, algae.mp3 00:04:30 231106_2212 computations by [massive, diverse] DNA coding segments.mp3 00:05:00 231106_2212 Computational biology journal - havent been reading my subscription.mp3 00:05:10 231106_2212 [learn, evolve] and Stephen Grossberg.mp3 00:05:57 231106_2212 does MindCode [reflect, teach us] about modern computing languages.mp3 00:06:55 231106_2212 what can evolution tell us about evolution.mp3 00:08:12 231106_2212 still missing a reference to arithmetic, [integer, real] numbers.mp3 see "$d_bin"'audio cut.sh' example # no change in codec, -to is stop position (time) : d_audio="$d_web"'Neural nets/Mind2023/voice musings/' ffmpeg -i "$d_audio"'231106_2212 Glenn Borchardts concept of infinity, avoid myopic thinking.mp3' -ss 00:01:22 -to 00:04:30 "$d_audio"'231106_2212 plants, fungi, algae.mp3' #08********08 #] 05Nov2023 Shapiro & Benenson +-----+ https://www.nature.com/articles/35106533 nature letters Published: 22 November 2001 Programmable and autonomous computing machine made of biomolecules Yaakov Benenson, Tamar Paz-Elizur, Rivka Adar, Ehud Keinan, Zvi Livneh & Ehud Shapiro Nature volume 414, pages 430–434 (2001)Cite this article Abstract Devices that convert information from one form into another according to a definite procedure are known as automata. One such hypothetical device is the universal Turing machine1, which stimulated work leading to the development of modern computers. The Turing machine and its special cases2, including finite automata3, operate by scanning a data tape, whose striking analogy to information-encoding biopolymers inspired several designs for molecular DNA computers4,5,6,7,8. Laboratory-scale computing using DNA and human-assisted protocols has been demonstrated9,10,11,12,13,14,15, but the realization of computing devices operating autonomously on the molecular scale remains rare16,17,18,19,20. Here we describe a programmable finite automaton comprising DNA and DNA-manipulating enzymes that solves computational problems autonomously. The automaton's hardware consists of a restriction nuclease and ligase, the software and input are encoded by double-stranded DNA, and programming amounts to choosing appropriate software molecules. Upon mixing solutions containing these components, the automaton processes the input molecule via a cascade of restriction, hybridization and ligation cycles, producing a detectable output molecule that encodes the automaton's final state, and thus the computational result. In our implementation 1012 automata sharing the same software run independently and in parallel on inputs (which could, in principle, be distinct) in 120 μl solution at room temperature at a combined rate of 109 transitions per second with a transition fidelity greater than 99.8%, consuming less than 10-10 W. +-----+ nature letters article Published: 28 April 2004 An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Nature volume 429, pages 423–429 (2004)Cite this article Abstract Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems1,2,3,4,5,6,7. Recently, simple molecular-scale autonomous programmable computers were demonstrated8,9,10,11,12,13,14,15 allowing both input and output information to be in molecular form. Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for ‘logical’ control of biological processes. Here we describe an autonomous biomolecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per microlitre and consists of three programmable modules: a computation module, that is, a stochastic molecular automaton12,13,14,15,16,17; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyse mRNA of disease-related genes18,19,20,21,22 associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug. +-----+ https://www.sciencedirect.com/science/article/abs/pii/S0022519321004045 Journal of Theoretical Biology Volume 537, 21 March 2022, 110984 Journal of Theoretical Biology An RNA-based theory of natural universal computation https://doi.org/10.1016/j.jtbi.2021.110984 Abstract Life is confronted with computation problems in a variety of domains including animal behavior, single-cell behavior, and embryonic development. Yet we currently do not know of a naturally existing biological system that is capable of universal computation, i.e., Turing-equivalent in scope. Generic finite-dimensional dynamical systems (which encompass most models of neural networks, intracellular signaling cascades, and gene regulatory networks) fall short of universal computation, but are assumed to be capable of explaining cognition and development. I present a class of models that bridge two concepts from distant fields: combinatory logic (or, equivalently, lambda calculus) and RNA molecular biology. A set of basic RNA editing rules can make it possible to compute any computable function with identical algorithmic complexity to that of Turing machines. The models do not assume extraordinarily complex molecular machinery or any processes that radically differ from what we already know to occur in cells. Distinct independent enzymes can mediate each of the rules and RNA molecules solve the problem of parenthesis matching through their secondary structure. In the most plausible of these models all of the editing rules can be implemented with merely cleavage and ligation operations at fixed positions relative to predefined motifs. This demonstrates that universal computation is well within the reach of molecular biology. It is therefore reasonable to assume that life has evolved – or possibly began with – a universal computer that yet remains to be discovered. The variety of seemingly unrelated computational problems across many scales can potentially be solved using the same RNA-based computation system. Experimental validation of this theory may immensely impact our understanding of memory, cognition, development, disease, evolution, and the early stages of life. +-----+ https://ietresearch.onlinelibrary.wiley.com/doi/10.1049/iet-nbt.2014.0020 IET Nanobiotechnology Volume 9, Issue 3 p. 122-135 Review Article Free Access Self-assembly: a review of scope and applications Anusha Subramony Iyer, Kolin Paul First published: 01 June 2015 https://doi.org/10.1049/iet-nbt.2014.0020 Abstract Self-assembly (SA) is the preferred growth mechanism in the natural world, on scales ranging from the molecular to the macro-scale. It involves the assembling of components, which governed by a set of local interaction rules, lead to the formation of a global minimum energy structure. In this survey, the authors explore the extensive research conducted to exploit SA in three domains; first, as a bottom-up approach to fabricate semiconductor heterostructures and nano-scale devices composed of carbon nanotubes and nanowires; second, for meso-scale assembly to build systems such as three-dimensional electrical networks and microelectromechanical systems by utilising capillary force, external magnetic field and so on as the binding force; and third, as an emerging means to achieve computing via tiling, biomolecular automata and logic gates. DNA, in particular, has been a molecule of choice because of its easy availability, biological importance and high programmability as a result of its highly specific component bases. #08********08 #] 02Nov2023 search "DNA transcription software" +-----+ https://www.genomics-online.com/resources/16/5021/free-tools-and-software-for-genomics-transcriptomics-crispr-co/ >> lots of stuff... +-----+ online free once-at-a-time DNA translation -> protein https://web.expasy.org/translate/ https://en.vectorbuilder.com/tool/dna-translation.html Input your DNA sequence below to retrieve the translated amino acid sequence. The sequence should begin with the start codon (ATG) and be in a multiple of 3 for a complete codon sequence. +-----+ https://www.khanacademy.org/science/ap-biology/gene-expression-and-regulation/transcription-and-rna-processing/a/overview-of-transcription Key points: Transcription is the first step in gene expression. It involves copying a gene's DNA sequence to make an RNA molecule. Transcription is performed by enzymes called RNA polymerases, which link nucleotides to form an RNA strand (using a DNA strand as a template). Transcription has three stages: initiation, elongation, and termination. In eukaryotes, RNA molecules must be processed after transcription: they are spliced and have a 5' cap and poly-A tail put on their ends. Transcription is controlled separately for each gene in your genome. RNA polymerase The main enzyme involved in transcription is RNA polymerase, which uses a single-stranded DNA template to synthesize a complementary strand of RNA. Specifically, RNA polymerase builds an RNA strand in the 5' to 3' direction, adding each new nucleotide to the 3' end of the strand. Stages of transcription Initiation. RNA polymerase binds to a sequence of DNA called the promoter, found near the beginning of a gene. Each gene (or group of co-transcribed genes, in bacteria) has its own promoter. Once bound, RNA polymerase separates the DNA strands, providing the single-stranded template needed for transcription. The promoter region comes before (and slightly overlaps with) the transcribed region whose transcription it specifies. It contains recognition sites for RNA polymerase or its helper proteins to bind to. The DNA opens up in the promoter region so that RNA polymerase can begin transcription. The promoter region comes before (and slightly overlaps with) the transcribed region whose transcription it specifies. It contains recognition sites for RNA polymerase or its helper proteins to bind to. The DNA opens up in the promoter region so that RNA polymerase can begin transcription. Elongation. One strand of DNA, the template strand, acts as a template for RNA polymerase. As it "reads" this template one base at a time, the polymerase builds an RNA molecule out of complementary nucleotides, making a chain that grows from 5' to 3'. The RNA transcript carries the same information as the non-template (coding) strand of DNA, but it contains the base uracil (U) instead of thymine (T). [What do 5' and 3' mean?] RNA polymerase synthesizes an RNA transcript complementary to the DNA template strand in the 5' to 3' direction. It moves forward along the template strand in the 3' to 5' direction, opening the DNA double helix as it goes. The synthesized RNA only remains bound to the template strand for a short while, then exits the polymerase as a dangling string, allowing the DNA to close back up and form a double helix. In this example, the sequences of the coding strand, template strand, and RNA transcript are: Coding strand: 5' - ATGATCTCGTAA-3' Template strand: 3'-TACTAGAGCATT-5' RNA: 5'-AUGAUC...-3' (the dots indicate where nucleotides are still being added to the RNA strand at its 3' end) RNA polymerase synthesizes an RNA transcript complementary to the DNA template strand in the 5' to 3' direction. It moves forward along the template strand in the 3' to 5' direction, opening the DNA double helix as it goes. The synthesized RNA only remains bound to the template strand for a short while, then exits the polymerase as a dangling string, allowing the DNA to close back up and form a double helix. In this example, the sequences of the coding strand, template strand, and RNA transcript are: Coding strand: 5' - ATGATCTCGTAA-3' Template strand: 3'-TACTAGAGCATT-5' RNA: 5'-AUGAUC...-3' (the dots indicate where nucleotides are still being added to the RNA strand at its 3' end) Termination. Sequences called terminators signal that the RNA transcript is complete. Once they are transcribed, they cause the transcript to be released from the RNA polymerase. An example of a termination mechanism involving formation of a hairpin in the RNA is shown below. #08********08 #] 02Nov2023 DNA, RNA, mRNA +-----+ search "genomics databases" https://www.ncbi.nlm.nih.gov/genbank/ https://www.ncbi.nlm.nih.gov/genome/ Effective May 2024, NCBI's Assembly resource will no longer be available. NCBI Assembly data can now be found on the NCBI Datasets genome pages. Learn more. >> good, but no reference to actual [DNA, RNA, steps] +-----+ search "RNA versus mRNA" +--+ https://www.dictionary.com/e/dna-vs-rna-vs-mrna-the-differences-are-vital/ “DNA” vs. “RNA” vs. “mRNA”: The Differences Are Vital January 8, 2021 DNA stands for “deoxyribonucleic acid.” DNA is arranged in the shape of a double helix, which resembles a twisted ladder. The “rungs” of the ladder consist of base pairs of substances known as nitrogen bases. You might remember the four bases from science class: adenine, thymine, guanine, and cytosine. These base pairs are the reason why DNA is so important to life: the ordering of the base pairs results in a specific genetic code called a gene. RNA stands for “ribonucleic acid.” RNA is a large molecule made from a single strand of DNA, and one of its main roles is to transfer the instructions needed to make proteins. DNA vs. RNA DNA and RNA are very similar. After all, RNA is supposed to be a copy of DNA. However, there are a few differences between the two molecules. The biggest difference is in their shape: DNA is a two-stranded molecule in the form of a double helix. RNA, on the other hand, is a single-stranded molecule. The other major difference is in the nitrogen bases: RNA shares three of DNA’s bases but has a substance known as uracil that replaces thymine when the DNA is copied. To put it very simply, uracil requires less energy to maintain than thymine, but the presence of thymine makes DNA more stable. mRNA “messenger RNA.”: is RNA that is read by ribosomes to build proteins (note: uracil) While all types of RNA are involved in building proteins, mRNA is the one that actually acts as the messenger. It is mRNA specifically that has the recipe for a protein. The mRNA is made in the nucleus and sent to the ribosome, like all RNA. Once it gets there, the mRNA bonds with the ribosome, which reads the mRNA’s nitrogen base sequence. Every three-bond sequence of mRNA relates to a specific amino acid, a “building block” of a protein. Amino acids must be arranged in a certain order to make a specific protein, and the mRNA has the blueprints that tell the ribosome which amino acids to get and how they should be arranged. Other types of RNA help the ribosome actually build the protein. Once the protein is built, the mRNA’s job is over and it will degrade. transfer RNA (tRNA) ribosomal RNA (rRNA) +--+ https://en.wikipedia.org/wiki/RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (Non-coding RNA) or by forming a template for the production of proteins (messenger RNA). Some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these active processes is protein synthesis, a universal function in which RNA molecules direct the synthesis of proteins on ribosomes. This process uses transfer RNA (tRNA) molecules to deliver amino acids to the ribosome, where ribosomal RNA (rRNA) then links amino acids together to form coded proteins. It has become widely accepted in science[1] that early in the history of life on Earth, prior to the evolution of DNA and possibly of protein-based enzymes as well, an "RNA world" existed in which RNA served as both living organisms' storage method for genetic information—a role fullfilled today by DNA, except in the case of RNA viruses—and potentially performed catalytic functions in cells—a function performed today by protein enzymes, with the notable and important exception of the ribosome, which is a ribozyme. Synthesis Synthesis of RNA is usually catalyzed by an enzyme—RNA polymerase—using DNA as a template, a process known as transcription. Initiation of transcription begins with the binding of the enzyme to a promoter sequence in the DNA (usually found "upstream" of a gene). The DNA double helix is unwound by the helicase activity of the enzyme. The enzyme then progresses along the template strand in the 3’ to 5’ direction, synthesizing a complementary RNA molecule with elongation occurring in the 5’ to 3’ direction. The DNA sequence also dictates where termination of RNA synthesis will occur.[27] Primary transcript RNAs are often modified by enzymes after transcription. For example, a poly(A) tail and a 5' cap are added to eukaryotic pre-mRNA and introns are removed by the spliceosome. There are also a number of RNA-dependent RNA polymerases that use RNA as their template for synthesis of a new strand of RNA. For instance, a number of RNA viruses (such as poliovirus) use this type of enzyme to replicate their genetic material.[28] Also, RNA-dependent RNA polymerase is part of the RNA interference pathway in many organisms.[29] In the early 1970s, retroviruses and reverse transcriptase were discovered, showing for the first time that enzymes could copy RNA into DNA (the opposite of the usual route for transmission of genetic information). For this work, David Baltimore, Renato Dulbecco and Howard Temin were awarded a Nobel Prize in 1975. In 1976, Walter Fiers and his team determined the first complete nucleotide sequence of an RNA virus genome, that of bacteriophage MS2.[79] 08********08 #] 07Mar2018 DNA storage for real computers This DIRECTLY relates to MindCode https://spectrum.ieee.org/the-human-os/biomedical/devices/dna-data-storage-gets-random-access?utm_source=thehumanosalert&utm_campaign=thehumanosalert-03-07-18&utm_medium=email Prachi Patel 20Feb2018 | 15:00 GMT DNA Data Storage Gets Random Access : Researchers have devised a system to recover targeted files from 200 megabytes of data encoded in DNA 08********08 #] 23Sep2019 HOX genes (architecture) https://en.wikipedia.org/wiki/Hox_gene ... Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment (e.g. legs, antennae, and wings in fruit flies), and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves. >> exactly what I need! from the sci-fi film "Annialation" 08********08 #] 11Aug2019 Architectures & Function Shapiro & Benenson - finite automata built from phages or something, programmed cell kill if cancerous Logic gates - use them! start very simple, improve over time McCulloch & Pitts - collect their functional architectures! State representations - especially inactive SNNs - simplest model - computer [CPU, memory, etc] - finite automata - is there anything besides Shapiro & Benenson? (probably - normal biology) - state - epigenetic (methylation), [express, modify] DNA coding availability - How many "states" do the various biological cells have? - what are the state categories for each type of cell? - what are the states of each state category? - states versus data - does data have to be [collected, structured, object oriented, networked]? - or can a general list do? (DNA, RNA work like that?) 08********08 #] 10Aug2019 mRNA circulation - soma to synapse reference from Alice Parker Karl E. Bauer, Inmaculada Segura, Imre Gaspar, Volker Scheuss, Christin Illig, Georg Ammer, Saskia Hutten, Eugénia Basyuk, Sandra M. Fernández-Moya, Janina Ehses, Edouard Bertrand, Michael A. Kiebler 25Jul2019 "Live cell imaging reveals 3′-UTR dependent mRNA sorting to synapses" Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-11123-x https://www.sciencedaily.com/releases/2019/07/190725102933.htm Neurobiology: Sushi for synapses Date: July 25, 2019 Source: Ludwig-Maximilians-Universität München The human brain is like a long-term construction site -- there's always something else to be done. This is certainly true of synapses, the functional links between nerve cells, which are constantly being strengthened, attenuated or demolished. Indeed, this process termed synaptic plasticity is the basis of our ability to store and recall information -- in other words, to learn. The instructions for the synthesis of necessary components, which are encoded in molecules known as messenger RNAs (mRNAs), are delivered to the specific synapses that need them by a specialized transport system. But how the blueprints reach their destinations is poorly understood. In order to learn more about the underlying mechanisms, cell biologist Professor Michael Kiebler and his group at the LMU Biomedical Center have now followed the transport of individual mRNAs to specific synapses. Their analysis shows that the same mRNA can be presented to potential addresses several times -- a system which the researchers compare to running sushi, the use of an 'endless' conveyor belt to enable patrons to pick and choose from the delicacies on offer. In order to serve the extensive network of synapses on a typically elongated process termed dendrite, the mRNAs must be transported from the nucleus in the cell body to the terminal branches at the end of the process. To monitor this process, the LMU team used cell cultures derived from neurons isolated from the hippocampus of the rat, which serves as a model for the human hippocampus. "We labelled specific mRNAs in living cells with a fluorescent dye, which enabled us to track their progress in real time," Kiebler explains. "This approach permitted us to determine, for the first time, whether or not a given molecule is delivered directly to a particular synapse, and whether different mRNAs are handled differently in this respect. In one case, we were able to follow how an mRNA entered one of the spine-like processes extended by a dendrite," he says. "Dendrites act as antennas that receive inputs from synapses on other cells." The observations revealed that one and the same mRNA may repeatedly circulate back and forth between the cell body and the nerve processes -- like sushi wending its way between the tables in a restaurant -- until it finds a synapse that needs it. Certain recognition sequences located in the segment of the mRNA that follows the stop codon (which marks the end of the protein-coding blueprint) serve as both the postage stamp and the address to direct the molecule to ensure that the molecule reaches the right region of the cell. "We have also demonstrated that, if the postage stamp is left intact, transport from the cell body to the neural processes is more effective and the mRNA is brought closer to the synapse than when it has been removed," says Kiebler. In addition, RNA-binding proteins such as Staufen2 play an important role in the regulation of mRNA transport by this cellular sorting system. Earlier studies had previously shown that Staufen2 is capable of binding several different mRNAs -- so that the same mechanism can distribute distinct mRNAs. In addition, the new report confirms early results which had suggested that uptake of the mRNA by the synapse depends on both the nature of the binding protein and the level of activity of the synapse. Taken together, the new data provide further details on the mechanisms underlying the delivery of proteins to synapses, and will have an impact on future efforts to understand the molecular basis of synaptic plasticity in mammals. 08********08 #] 25Jul2019 Alice Parker. Spiking Neural Networks & DNA. USC. Los Angeles Alice Parker. Spiking Neural Networks & DNA. USC. Los Angeles. USA - Mindcode Lunch at restaurant after IJCNN2019 in Budapest I sent an email about DNA-SNNs /media/bill/SWAPPER/Projects - big/MindCode/Howell 050824 Junk DNA & NeuralNetworks, conjecture on directions and implications, IJCNN05 workshop panel presentation.ppt /media/bill/SWAPPER/Projects - big/MindCode/Howell 060215 Genetic specification of neural networks, draft concepts and implications.odt /media/bill/SWAPPER/Projects - big/MindCode/Howell 060215 Genetic specification of neural networks, draft concepts and implications.pdf /media/bill/SWAPPER/Projects - big/MindCode/Howell 060716 Genetic specification of recurrent neural networks, Initial thoughts, WCCI 2006 paper 1341.ppt /media/bill/SWAPPER/Projects - big/MindCode/Howell 060721 Genetic Specification of Recurrent Neural Networks Initial Thoughts, WCCI 2006 presentation.ppt /media/bill/SWAPPER/Projects - big/MindCode/Howell 150225 - MindCode Manifesto.odt /media/bill/SWAPPER/Neural Nets/Confabulation/Howell 110903 - Confabulation Theory, Plausible next sentence survey.pdf /media/bill/SWAPPER/Website/Social media/Howell 110902 – Systems design issues for social media.pdf /media/bill/SWAPPER/Website/Social media/Howell 111006 – Semantics beyond search.pdf /media/bill/SWAPPER/Website/Social media/Howell 111117 - How to set up & use data mining with Social media.pdf /media/bill/SWAPPER/Website/Social media/Howell 111230 – Social graphs, social sets, and social media.pdf http://www.billhowell.ca/Neural%20nets/MindCode/Howell%20050824%20Junk%20DNA%20&%20NeuralNetworks,%20conjecture%20on%20directions%20and%20implications,%20IJCNN05%20workshop%20panel%20presentation.ppt http://www.billhowell.ca/Neural%20nets/MindCode/Howell%20060215%20Genetic%20specification%20of%20neural%20networks,%20draft%20concepts%20and%20implications.odt http://www.billhowell.ca/Neural%20nets/MindCode/Howell%20060215%20Genetic%20specification%20of%20neural%20networks,%20draft%20concepts%20and%20implications.pdf http://www.billhowell.ca/Neural%20nets/MindCode/Howell%20060716%20Genetic%20specification%20of%20recurrent%20neural%20networks,%20Initial%20thoughts,%20WCCI%202006%20paper%201341.pdf http://www.billhowell.ca/Neural%20nets/MindCode/Howell%20060721%20Genetic%20Specification%20of%20Recurrent%20Neural%20Networks%20Initial%20Thoughts,%20WCCI%202006%20presentation.ppt http://www.billhowell.ca/Neural%20nets/MindCode/Howell%20150225%20-%20MindCode%20Manifesto.odt http://www.billhowell.ca/Social%20media/Howell%20111230%20–%20Social%20graphs,%20social%20sets,%20and%20social%20media.pdf http://www.billhowell.ca/Social%20media/Howell%20110902%20–%20Systems%20design%20issues%20for%20social%20media.pdf http://www.billhowell.ca/Social%20media/Howell%20111006%20-%20SPINE,%20Semantics%20beyond%20search.pdf http://www.billhowell.ca/Social%20media/Howell%20111117%20-%20How%20to%20set%20up%20&%20use%20data%20mining%20with%20Social%20media.pdf 08********08 #] 07Mar2018 DNA storage for real computers This DIRECTLY relates to MindCode https://spectrum.ieee.org/the-human-os/biomedical/devices/dna-data-storage-gets-random-access?utm_source=thehumanosalert&utm_campaign=thehumanosalert-03-07-18&utm_medium=email Prachi Patel 20Feb2018 | 15:00 GMT DNA Data Storage Gets Random Access : Researchers have devised a system to recover targeted files from 200 megabytes of data encoded in DNA # enddoc