The tipping point (revisited): 75,000 publications

Session 3: Host-virus interactions: structure and function Session 7: Phage therapy I, fundamentals Session 8: Phage therapy II, application

See also: Superbugs, Bacteriophages and Phage Therapy: An Interview with James Kohl Published on 17 May 2017
First responders may want to see:

Session 8: Phage therapy II, application
Phage therapy discussion panel: Direction to the future
Opening talk by Jerome Gabard:

PhagoBurn: efficacy and tolerability of a phage mix produced… to treat Pseudomonas aeruginosa infected burn wounds

See also: Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system
If the weekend resurrection of the bacterial flagellum in Pseudomonas fluorescens was used as an indicator of how effective phage therapy can be in the context of other potential pathogens, extending the time for resurrection from 96 hrs to a few more days could be linked from the availability of quantized energy as information to viral latency via fluorescence.
See also: Royal Society: The Public Evolution Summit
Page 12

… evolution of genome invading RNA networks that edit host g… Witzany is organizing a conference symposium for July 2018 “Evolution-genetic innovations without error replication”

This is how evolutionary theorists nearly caused the death of my brother. Most of them still think that error replication can be prevented by something besides the nutrient-dependent pheromone-controlled physiology of reproduction in bacteria (like C. diff). They will continue their killing spree until intelligent serious scientists stop them, but the serious scientists can’t do it alone. The serious scientists are Combating Evolution to Fight Disease. Here is what they are up against.
EVOLUTION – Genetic Novelty/Genomic Variations by RNA-Networks and Viruses
Guenther Witzany (organizer) Introduction: A new Definition of Life will lead to a new Theory of Evolution

Three levels of biocommunication (cell-cell communication, RNA-RNA/DNA/Protein interactions, virosphere) are essential for organizing and coordinating all life processes. If one level is completely missing, we could not speak seriously of life.

The interactions between these three levels (cells, RNA Networks, virosphere) sheds light onto evolutionary processes depending on genetic novelty and genomic variations beyond the error replication (mutations) narrative.

Poster presentation: Sophie Juliane Veigl

Philosophical as well as biological theories of the self / identity rely very much on a theory of evolution by random (DNA-based) selection. However, the small RNA based paradigm of  immunological memory opens up a different perspectives for considering identity.

See for comparison, our review of food energy-dependent pre-mRNA-mediated pheromone-controlled cell type differentiation: From Fertilization to Adult Sexual Behavior (1996)

Parenthetically it is interesting to note even the yeast Saccharomyces cerevisiae has a gene-based equivalent of sexual orientation (i.e., a-factor and alpha-factor physiologies). These differences arise from different epigenetic modifications of an otherwise identical MAT locus (Runge and Zakian, 1996; Wu and Haber, 1995).

This conference organizer clearly states that a new Definition of Life and a new Theory of Evolution must replace old definitions and theories. The fact that only one poster presentation directly challenged the pseudoscientific nonsense touted by neo-Darwinian theorists attests to the amount of human idiocy that has been expressed in the presentations of others.
With few exceptions, I give you excerpts (below) that attest to that nonsense. There is no mention of more than 75,000 published works that link the quantized energy-dependent creation of microRNAs to biophysically constrained viral latency and all biodiversity on Earth via the physiology of pheromone-controlled reproduction in species from microbes to humans.
One attempt to place natural selection for quantized energy-dependent codon optimality falls short, when Eric Westhof places his integrative review back into the context of sophisticated co-evolution patterns. The patterns link the microRNA-mediated creation of enzymes from cellular metabolism to protein homeostasis in the context of biophysically constrained viral latency and sympatric speciation.

Eric Westhof

An integrative view of all the complex interaction networks between messenger RNA, transfer RNA, and ribosomal RNA is described: the stability of codon-anticodon trimers, the conformation of the anticodon stem-loop of transfer RNA, the modified nucleotides, and the interactions with bases of ribosomal RNA at the decoding site. An information-rich, alternative representation of the codon table is derived. The new organization of the 64 codons is circular with an asymmetric distribution of codons and leads to a clear segregation between GC-rich 4-codon boxes and AU-rich 2:2-codon and 3:1-codon boxes. The advantage of integrating data in this circular decoding system is that all transfer RNA sequence variations can be visualized, within an internal structural and energy framework, for each organism and anticodon. Within this new representation, the multiplicity and complexity of nucleotide modifications, especially at base positions 34 and 37 in the anticodon loop, segregate meaningfully and correlate well with the necessity to stabilize AU-rich codon-anticodon pairs and to avoid miscoding in split codon boxes. Further, chemical modifications of base U34 are critical to decode purineending codons in split codon boxes. These chemical modifications allow for diversity in codon usage depending on the genomic GC content as well as on the number and types of isoacceptor tRNAs. This structure-based network of interactions results in an energetically uniform decoding of all native and fully modified tRNAs. Depending on presence or levels of modifications, translation can adapt to the cellular constraints. The evolution and expansion of the genetic code is viewed as originally based on GC content and “old” amino acids (like Ala, Gly, Pro) with the progressive introduction of A/U codons and additional amino acid decoding together with tRNA modifications and the modification enzymes. Because of the coupling with metabolism and enzymatic machineries, although universal, the genetic code is not translated identically and codon use and bias differ between organisms in the three kingdoms of life. To decipher diversely but efficiently the genetic code, cells developed sophisticated co-evolution patterns between transfer RNA pools and modifications, anchored in the cellular metabolic enzymatic pathways and guaranteeing protein homeostasis.

For comparison see: microRNA Items: 1 to 20 of ~ 75,000
See also: Download Programme + Abstracts >
Luis Villarreal

…if we generalize these RNA virus features, we open a new conceptual door to collective behaviors from which interacting RNA networks (and communication) naturally emerge. From this perspective, we can propose a pathway for the origin of RNA consortia based life. We can also account for why various distinct retroviruses were involved in acquisition of complex phenotype, such the species specific origin of mammalian placentas or programming stem cells.

Gustavo Caetano-Anollés

The evolution of structure in biology is driven by accretion and change.

Irene Chen

Evolution and emergence of functional RNA: mapping the fitness landscape’ …we study the emergence and evolution of functional RNAs.

Jan Attig

Retrotransposons are self-replicating genetic elements and pervasive in mammalian genomes.

Felix Broecker

We conclude that viruses/transposable elements have majorly contributed to the evolution of pro- and eukaryotic immune systems through various mechanisms, often involving RNase H-like enzymes.

Chantal Abergel

The resulting virophage particles are composed of a surprisingly complex, albeit consistent, set of virophage, host virus and transpoviron-encoded proteins. Symmetrically, mobilome proteins were found in the host virus particles testifying to an intricate “ménage à trois”. Our results indicate that transpovirons propagate both through virophage and host virus particles and exhibit clade selectivity.

Jean-Michel Claverie

…de novo gene creation could contribute to the evolution of the giant pandoravirus genomes.

Reynald Gillet

From these modern data, I will then present a model in which proto-tmRNAs were the first molecules on earth to support non-random protein synthesis, explaining the emergence of early genetic code. In fact, an ancient tmRNA could be the missing link between the first mRNA and tRNA molecules and modern ribosome-mediated protein synthesis.

Eugene V. Koonin

Host-parasite interactions appear to have played key roles in major evolutionary transitions such as the origin of the first cells, eukaryotic cells, and multicellular organisms.

Dušan Kordiš

The origin of placental mammal-specific innovations and adaptations, such as placenta and newly evolved brain functions, was most probably connected to the regulatory wiring of domesticated genes and their rapid fixation in the ancestor of placental mammals.

Erez Levanon

Both recoding and noncoding events have implications for genome evolution and, when deregulated, may lead to disease.

Karin Moelling

Loss of genes is underestimated in its importance as evolutionary force known in mitochondria, chloroplasts, Rickettsia, plants, and retroviruses (retroelements).

Mariusz Nowacki

Probably the most striking evidence for transgenerational inheritance is the RNA-mediated programming of genome content in ciliates, where maternal small RNAs guide DNA rearrangement in the genome of the progeny. This epigenetic transmission of information between maternal nuclei and the genome of the offspring mediates large-scale elimination of active and inactive transposable elements, which is not only required for genome stability but also enables genetic changes be passed on to the offspring.

David Prangishvili

Unusual features of this group of viruses include incredible diversity of elaborate virion architectures, many of which have never been observed among DNA viruses of Bacteria or Eukaryotes, as well as their genetic content, which in some cases is literally terra incognita, without a single gene with homologs in extant databases [3].

Forest Rohwer

…phage, released from lysogens in the microbome, form a bacterial selective, adaptive immune system protecting the mucosal surfaces of animals. This is probably the origin of the selective immune system. Underlying both of these phenomena are an ecological process called Piggyback-the-Winner that facilitates evolutionary, Red Queen dynamics.

James A. Shapiro

…we know that many life-history events lead to rapid and non-random evolutionary change mediated by specific cellular functions. These include cell mergers and activation of natural genetic engineering by stress, infection and interspecific hybridization. In addition, we know of molecular mechanisms for transmitting life history information across generations through gametes. These discoveries require a new agenda for evolutionary experiments to determine the genomic impacts of abiotic stresses, biotic interactions, and sensory inputs from environmental conditions.

Corrado Spadafora

…chromatin organization can be rapidly reformatted and acquire roles in cell fate determination that can contribute to adaptive processes over evolutionary time.

Nobuto Takeuchi

…conflicting multilevel evolution forms a positive feedback loop with the asymmetric flow of information between the molecules, which induces the division of labor between primordial genomes and enzymes. Our results provide a novel evolutionary explanation for the origin of the fundamental molecular asymmetries underlying all life.

Andreas Werner

Transcriptional changes are paralleled by epigenetic modifications. These studies are complemented with HEK293 cells that carry transcriptional termination signals either in SLC34A1 or PFN3 upstream of the potential RNA overlaps.

Bojan Zagrovic

…our results support as well as redefine the stereochemical hypothesis concerning the origin of the genetic code, the idea that it evolved from direct interactions between amino acids and the appropriate bases. Moreover, our findings support the possibility of direct, complementary, co-aligned interactions between mRNAs and their cognate proteins even in present-day cells, especially if both are unstructured, with implications extending to different facets of nucleic-acid/protein biology.

EVOLUTION – Speakers
Chantal Abergel >
Centre National de la Recherche Scientifique & Aix-Marseille University, Marseille, France
Jan Attig >
Retroviral Immunology, The Francis Crick Institute, London, UK
Gustavo Caetano Anolles >
Department of Crop Sciences, Evolutionary Bioinformatics Laboratory, University of Illinois at Urbana-Champaign Urbana, USA.
Felix Broecker >
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA
Irene Chen >
Department of Chemistry & Biochemistry, University of California, Santa Barbara, USA
Julian Chen >
Department of Chemistry and Biochemistry, Arizona State University, Tempe, USA
Jean-Michel Claverie >
Centre National de la Recherche Scientifique & Aix-Marseille University, Marseille, France
Bryan Cullen >
Department of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, USA
Valerian Dolja >
Department of Botany and Plant Pathology, Oregon State University, Corvallis, USA
Matthias Fischer >
Max Planck Institute for Medical Research, Department of Biomolecular Mechanisms, Heidelberg, Germany
David Gilmer >
Institut de biologie moléculaire des plantes, Integrative virology, Strasbourg, France
Reynald Gillet >
Université de Rennes 1, Translation and Folding Team, Rennes cedex, France Institut Universitaire de France
Jordi Gomez >
Instituto de Parasitología y Biomedicina ‘López-Neyra’ (CSIC), Granada, Spain
Norikazu Ichihashi >
Graduate School of Information Science and Technology, Osaka University, Osaka, Japan
Matti Jalasvuori >
Centre of Excellence in Biological Interactions, Department of Biological and Environmental Science, University of Jyväskylä, Finland
Eugene Koonin >
National Center for Biotechnology Information, National Library of Medicine, Bethesda, USA.
Dusan Kordis >
Department of Molecular and Biomedical Sciences, Josef Stefan Institute, Ljubljana, Slovenia
Mart Krupovic >
Unit BMGE, Department of Microbiology, Institut Pasteur, Paris, France
Erez Levanon >
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
Jeff Miller >
California NanoSystems Institute, University of California, Los Angeles, USA
Tomohiro Mochizuki >
Earth-Life Science Institute, Tokyo Institute of Technology, Tokyo, Japan
Karin Moelling >
Max Planck Institute for molecular Genetics, Berlin, Germany
Sabine Müller >
Universität Greifswald, Institut für Biochemie , Greifswald , Germany
Ulrich Müller >
Department of Chemistry & Biochemistry, University of California, San Diego, USA
Mariusz Nowacki >
Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland
David Prangishvili >
Department of Microbiology, BMGE, Institut Pasteur, Paris, France
Lennart Randau >
Max Planck Institute for Terrestrial Microbiology, Marburg, Germany
Forest Rohwer >
Department of Biology, San Diego State University, San Diego, CA, USA
Hervé Seligmann >
Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Aix-Marseille Université, Marseille, France
James Shapiro >
Department of Biochemistry and Molecular Biology , University of Chicago , IL , USA
Corrado Spadafora >
Institute of Translational Pharmacology, CNR, Rome, Italy
Jonathan Stoye >
Retrovirus-Host Interactions, The Francis Crick Institute, London, UK
Nobuto Takeuchi >
Department of Basic Science, University of Tokyo, Tokyo, Japan
Keizo Tomonaga >
Laboratory of RNA Viruses, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Japan
Luis P. Villarreal >
Center for Virus Research, University of California, Irvine, Irvine, CA, USA
Andreas Werner >
RNA biology group, Institute for Cell and Molecular Biosciences, Newcastle University, UK
Eric Westhof >
Architecture and Reactivity of RNA, Institute of Molecular and Cellular Biology of the CNRS, University of Strasbourg, France
Bojan Zagrovic >
Department of Structural and Computational Biology, Max F. Perutz Laboratories, Vienna, Austria
Steven Zimmerly >
Department of Biological Sciences, University of Calgary, Calgary, Canada