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An illustrated new view of the ontological basis and value of ALL life in health and disease

“The world is perfect, and the human opportunity is to see that and conform to that fact.” – Huston Smith

“A man only becomes wise when he begins to calculate the approximate depth of his ignorance.” – Gian Carlo Menotti

Timelines

Adapted from: https://en.wikipedia.org/wiki/Timeline_of_human_evolution


The Fundamental Units of Life are the Energy Miners – All Microorganisms and the Mitochondria and Chloroplasts from which they are derived

Serial_endosymbiosis

Adapted from: https://en.wikipedia.org/wiki/Symbiogenesis

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Adapted from: http://www.citruscollege.edu/lc/archive/biology/Pages/Chapter03-Rabitoy.aspx


A New View of the Tree of Life includes the Endosymbionts (Mitochondria and Chloroplasts) in Eukaryotes and the uncultivable Exosymbionts labeled Candidate Phyla Radiation

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Animals, fungi, and plants represent a tiny fraction of the diversity shown on the new Tree of Life.

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Adapted from: A field guide for the new Tree of Life

Original paper can be found here: https://www.nature.com/articles/nmicrobiol201648

Bacteria make up nearly two-thirds of all biodiversity on Earth, half of them uncultivable

Scientists have dramatically expanded the tree of life, which depicts the variety and evolution of life on Earth, to account for thousands of new microscopic life forms discovered over the past 15 years. The expanded view finally gives bacteria and Archaea their due, showing that about two-thirds of all diversity on Earth is bacterial — half bacteria that cannot be isolated and grown in the lab — while nearly one-third is Archaeal.

Adapted from: Wealth of unsuspected new microbes expands tree of life


The Planetary Life-Ground is Enriched by the Root Microbiome

rhizodeposition

“In the figure above, sunlight and carbon dioxide from the atmosphere are absorbed by the leaves in the plant and converted to fixed carbon. This carbon travels down into the roots of the plant, where some travels back up to the leaves. The fixed carbon traveling to the root is radiated outward into the surrounding soil where microbes use it as food for growth. In return, microbes attach to the plant root where it improves the roots access to nutrients and its resistance to environmental stress and pathogens. In specific plant/root symbiotic relationships, the plant root secretes flavonoids into the soil which is sensed by microbes, where these microbes release nod factors to the plant root which promotes the infection of the plant root. These unique microbes carry out nitrogen fixation in root nodules, which supplies nutrients to the plant.”

Adapted from: https://en.wikipedia.org/wiki/Root_microbiome


The Wood Wide Web of fungal mycelia is the “Neural Network” of the Planetary Life-Ground

Nature’s internet: how trees talk to each other in a healthy forest | Suzanne Simard | TEDxSeattle

Published on Feb 2, 2017

This fascinating talk presents the scientific research that shows the interconnectedness of life in the forest ecosystem. It takes us beneath the forest floor where we learn how trees are communicating and exchanging resources. Going beyond the simple view of a forest as a resource to be exploited, it presents the forest as a complex network of life. Her examination of the relationships that make up the complexity of nature present compelling support for the idea that “We are all one”

Suzanne Simard studies the surprising and delicate complexity in nature. Her main focus is on the below-ground fungal networks that connect trees and facilitate underground inter-tree communication and interaction. Her team’s analysis revealed that the fungi networks move water, carbon and nutrients such as nitrogen between and among trees as well as across species. The research has demonstrated that these complex, symbiotic networks in our forests — at the hub of which stand what she calls the “mother trees” — mimic our own neural and social networks. This groundbreaking work on symbiotic plant communication has far-reaching implications in both the forestry and agricultural industries, in particular concerning sustainable stewardship of forests and the plant’s resistance to pathogens. She works primarily in forests, but also grasslands, wetlands, tundra and alpine ecosystems.


The Organismal Life-Ground is Enriched by the Gut Microbiome

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Adapted from: http://www.gutmicrobiotaforhealth.com/en/gut-microbiome-stable-ever-changing/


A Map of Diversity in the Human Microbiome

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Adapted from: http://huttenhower.sph.harvard.edu/metaphlan

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Adapted from: https://en.wikipedia.org/wiki/Human_Microbiome_Project


The Rise of Mitochondria in Medicine

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Normalized proportions of published Medline-indexed medical articles from 1980 to January 1, 2016, related to various cellular components: mitochondria, nucleus, endoplasmic reticulum (ER), and Golgi apparatus. Note the increase in mitochondria-related publications following the publication of polymerase chain reaction (PCR) in 1986, the discovery of the first pathogenic mtDNA mutation/deletion in the 1988, and steady rise since the year 2000. In comparison, the number of publications about the cell nucleus has steadily decreased in the ‘post-genomic era’ following the completion of the human genome project in 2001, which demonstrated that the long searched genetic origin of common chronic diseases is likely not encoded in nuclear genes. Data for this figure was extracted from Medline/PubMed by searching the term “medicine” in combination with either “nucleus”, “mitochondri*”, “endoplasmic reticulum”, or “Golgi”.

mitmed

Multifaceted mitochondrial pathogenesis. (A) Somatic tissues contain 100–1000’s of mitochondrial DNA (mtDNA) molecules each, such that a mixture of normal and mutated copies can coexist in a state of heteroplasmy. (B) The mitochondrial genome, containing 37 genes essential to respiratory chain assembly and function. (C) mtDNA heteroplasmy for the most common pathogenic MELAS-causing m.3243A>G mutation of the tRNALeu(UUR) gene causes genome-wide transcriptional reprogramming; data adapted from (Picard et al., 2014b). (D) Mitochondrial signals promoting cancer initiation and progression. (E) Abnormal mitochondrial function and positioning alters multiple components of the nervous system. (F) Metabolic programming of immune cell differentiation and proliferation into anti- and pro-inflammatory phenotypes, driven by the balance of oxidative phosphorylation (OXPHOS) vs. glycolysis and mitochondrial reactive oxygen species (mtROS).

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Multi-level organization of mitochondrial molecular composition, structures, functions, and signaling roles within the cell. These nested facets of mitochondrial functions are depicted hierarchically in a Maslow-type pyramidal model with the most basic determinants at the bottom and more complex emergent processes above. These facets of mitochondrial and cellular functions (first dimension) are regarded as determinants of higher-level physiological functions (second dimension), which in turn influence systems-level functions (third dimension) that contribute to clinical outcomes and mortality.

Figures above adapted from: The rise of mitochondria in medicine


The microbiome and mitochondria communicate with each other

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Microbiota and pathogenic bacteria target host cell through ROS regulation and DNA insertion. Commensal and pathogenic bacteria release factors that modulate cell ROS concentration by acting on mitochondrial activity. Pathogen-associated molecular patterns activate the pattern recognition receptors (PRR) and induce mitochondrial ROS production and nuclear gene expression. In parallel, commensal bacteria release formylated protein recognized by the formylated protein receptor (FPR) that activates NADPH oxidase (NOX) and increases cytoplasmic ROS that are sensed by redox sensor proteins. High ROS production is able to trigger an inflammatory response and increases cell oxidative stress. Furthermore, cell stress can trigger mitochondrial and bacterial DNA insertion in the nuclear genome leading to alteration of cellular gene expression. (1) Arrow 1: mitochondrial DNA insertion into the nucleus. (2) Arrow 2: bacterial DNA insertion into the nucleus.

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Microbiota release metabolites that promote or decrease mitochondrial energy metabolism. Nitric oxide (NO) is able to inhibit the tricarboxylic acid cycle (TCA) by reducing acetyl-CoA production. In addition high production of hydrogen sulfide (H2S) by the microbiota inhibit complex IV of the electron transfer chain (ETC). In contrast, short chain fatty acids (SCFAs), in particular butyrate, are able to fuel the TCA cycle. In parallel, SCFAs can induce release of anti-inflammatory IL-10 cytokines and signaling hormone GLP-1 to reduce energy intake.

Figures adapted from: Microbiota–mitochondria inter-talk: consequence for microbiota–host interaction


The mitochondria in the body communicate with each other and with the microbiome via the nervous, endocrine and immune systems

nsdiagram

Adapted from: https://en.wikipedia.org/wiki/Nervous_system

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Diagram of the interactions between the brain and components of the endocrine and immune systems. The ability of the brain to alter immune system function via a variety of endocrine pathways and the autonomic nervous system is emphasized, and the effects of peptides and cytokines produced by the immune system on immune cells and the brain is indicated. A, adrenaline (epinephrine); ACTH, adrenocorticotrophic hormone; CRF, corticotrophin‐releasing factor; CS, corticosteroids; Enk, enkephalins; GH, growth hormone; NA, noradrenaline (norepinephrine); NPY, neuropeptide Y; SP, substance P; TNFα, tumour necrosis factor α. Modified from Dunn (1995).

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Diagram of the relationship of the brain, the hypothalamic–pituitary–adrenocortical (HPA) axis and immune cells. Interleukin‐1 (IL‐1), and possibly other cytokines, produced by lymphocytes during the immune response activates noradrenergic (NA) projections from the brainstem to the hypothalamic paraventricular nucleus (PVN). This input activates the HPA axis, stimulating the release of corticotrophin‐releasing factor (CRF) from the median eminence of the hypothalamus. CRF stimulates the secretion of adrenocorticotrophic hormone (ACTH) from the anterior lobe of the pituitary, which in turn activates the adrenal cortex to synthesize and secrete glucocorticoid hormones. The glucocorticoids may provide a negative feedback on cytokine production by lymphocytes. Modified from Dunn (1995).

Figures adapted from: Nervous and Immune System Interactions


Connecting the Social Determinants of Diseases with Mitochondrial Dysfunction

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Figures adapted from: Allostatic load and comorbidities: A mitochondrial, epigenetic, and evolutionary perspective


Are the pleomorphic mitochondria the pleomorphic microzyma of Antoine Bernard’s cellular/terrain theory of disease?

two diseaseAdapted from: Shifting the Paradigm

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