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Life, Volume 10, Issue 2 (February 2020) – 12 articles

Cover Story (view full-size image): Classical resistance classifications are very useful for epidemiological purposes, but they may not correlate well with clinical outcomes. Therefore, several novel classification criteria have recently been introduced for Gram-negative bacteria. Microbiological and resistance data were collected for urinary tract infections (UTIs) retrospectively, corresponding to the 01 January 2008–31 December 2017 period. The introduction of difficult-to-treat resistance (and its modifications detailed in this study) to the bedside and in clinical practice will definitely lead to substantial benefits in the assessment of the significance of bacterial resistance in human therapeutics. View this paper
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11 pages, 227 KiB  
Book Review
Getting Beyond the Toy Domain. Meditations on David Deamer’s “Assembling Life”
by William Bains
Life 2020, 10(2), 18; https://doi.org/10.3390/life10020018 - 18 Feb 2020
Cited by 2 | Viewed by 3909
Abstract
David Deamer has written another book, Assembling Life, on the origin of life. It is unapologetically polemic, presenting Deamer’s view that life originated in fresh water hydrothermal fields on volcanic islands on early Earth, arguing that this provided a unique environment not just [...] Read more.
David Deamer has written another book, Assembling Life, on the origin of life. It is unapologetically polemic, presenting Deamer’s view that life originated in fresh water hydrothermal fields on volcanic islands on early Earth, arguing that this provided a unique environment not just for organic chemistry but for the self-assembling structure that drive that chemistry and form the basis of structure in life. It is worth reading, it is an advance in the field, but is it convincing? I argue that the Origin of Life field as a whole is unconvincing, generating results in Toy Domains that cannot be scaled to any real world scenario. I suggest that, by analogy with the history of artificial intelligence and solar astronomy, we need much more scale, and fundamentally new ideas, to take the field forward. Full article
(This article belongs to the Section Origin of Life)
14 pages, 1228 KiB  
Article
Quantifying the Performance of Micro-Compartmentalized Directed Evolution Protocols
by Adèle Dramé-Maigné, Anton S. Zadorin, Iaroslava Golovkova and Yannick Rondelez
Life 2020, 10(2), 17; https://doi.org/10.3390/life10020017 - 13 Feb 2020
Cited by 4 | Viewed by 3393
Abstract
High-throughput, in vitro approaches for the evolution of enzymes rely on a random micro-encapsulation to link phenotypes to genotypes, followed by screening or selection steps. In order to optimise these approaches, or compare one to another, one needs a measure of their performance [...] Read more.
High-throughput, in vitro approaches for the evolution of enzymes rely on a random micro-encapsulation to link phenotypes to genotypes, followed by screening or selection steps. In order to optimise these approaches, or compare one to another, one needs a measure of their performance at extracting the best variants of a library. Here, we introduce a new metric, the Selection Quality Index (SQI), which can be computed from a simple mock experiment, performed with a known initial fraction of active variants. In contrast to previous approaches, our index integrates the effect of random co-encapsulation, and comes with a straightforward experimental interpretation. We further show how this new metric can be used to extract general protocol efficiency trends or reveal hidden selection mechanisms such as a counterintuitive form of beneficial poisoning in the compartmentalized self-replication protocol. Full article
(This article belongs to the Section Evolutionary Biology)
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17 pages, 5081 KiB  
Article
Characterization of Resistance in Gram-Negative Urinary Isolates Using Existing and Novel Indicators of Clinical Relevance: A 10-Year Data Analysis
by Márió Gajdács, Zoltán Bátori, Marianna Ábrók, Andrea Lázár and Katalin Burián
Life 2020, 10(2), 16; https://doi.org/10.3390/life10020016 - 11 Feb 2020
Cited by 66 | Viewed by 7678
Abstract
Classical resistance classifications (multidrug resistance [MDR], extensive drug resistance [XDR], pan-drug resistance [PDR]) are very useful for epidemiological purposes, however, they may not correlate well with clinical outcomes, therefore, several novel classification criteria (e.g., usual drug resistance [UDR], difficult-to-treat resistance [DTR]) were introduced [...] Read more.
Classical resistance classifications (multidrug resistance [MDR], extensive drug resistance [XDR], pan-drug resistance [PDR]) are very useful for epidemiological purposes, however, they may not correlate well with clinical outcomes, therefore, several novel classification criteria (e.g., usual drug resistance [UDR], difficult-to-treat resistance [DTR]) were introduced for Gram-negative bacteria in recent years. Microbiological and resistance data was collected for urinary tract infections (UTIs) retrospectively, corresponding to the 2008.01.01–2017.12.31. period. Isolates were classified into various resistance categories (wild type/susceptible, UDR, MDR, XDR, DTR and PDR), in addition, two new indicators (modified DTR; mDTR and mcDTR) and a predictive composite score (pMAR) were introduced. Results: n = 16,240 (76.8%) outpatient and n = 13,386 (69.3%) inpatient UTI isolates were relevant to our analysis. Citrobacter-Enterobacter-Serratia had the highest level of UDR isolates (88.9%), the Proteus-Providencia-Morganella group had the highest mDTR levels. MDR levels were highest in Acinetobacter spp. (9.7%) and Proteus-Providencia-Morganella (9.1%). XDR- and DTR-levels were higher in non-fermenters (XDR: 1.7%–4.7%. DTR: 7.3%–7.9%) than in Enterobacterales isolates (XDR: 0%–0.1%. DTR: 0.02%–1.5%). Conclusions: The introduction of DTR (and its’ modifications detailed in this study) to the bedside and in clinical practice will definitely lead to substantial benefits in the assessment of the significance of bacterial resistance in human therapeutics. Full article
(This article belongs to the Section Microbiology)
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20 pages, 2850 KiB  
Article
Coupling of Cell Division and Differentiation in Arabidopsis thaliana Cultured Cells with Interaction of Ethylene and ABA Signaling Pathways
by Galina V. Novikova, Natalia S. Stepanchenko, Anna A. Zorina, Alexander V. Nosov, Victor Y. Rakitin, Igor E. Moshkov and Dmitry A. Los
Life 2020, 10(2), 15; https://doi.org/10.3390/life10020015 - 10 Feb 2020
Cited by 6 | Viewed by 4033
Abstract
Recent studies indicate direct links between molecular cell cycle and cell differentiation machineries. Ethylene and abscisic acid (ABA) are known to affect cell division and differentiation, but the mechanisms of such effects are poorly understood. As ethylene and ABA signaling routes may interact, [...] Read more.
Recent studies indicate direct links between molecular cell cycle and cell differentiation machineries. Ethylene and abscisic acid (ABA) are known to affect cell division and differentiation, but the mechanisms of such effects are poorly understood. As ethylene and ABA signaling routes may interact, we examined their involvement in cell division and differentiation in cell tissue cultures derived from several Arabidopsis thaliana plants: wild type (Col-0), and ethylene-insensitive mutants etr1-1, ctr1-1, and ein2-1. We designed an experimental setup to analyze the growth-related parameters and molecular mechanisms in proliferating cells upon short exposure to ABA. Here, we provide evidence for the ethylene–ABA signaling pathways’ interaction in the regulation of cell division and differentiation as follows: (1) when the ethylene signal transduction pathway is functionally active (Col-0), the cells actively proliferate, and exogenous ABA performs its function as an inhibitor of DNA synthesis and division; (2) if the ethylene signal is not perceived (etr1-1), then, in addition to cell differentiation (tracheary elements formation), cell death can occur. The addition of exogenous ABA can rescue the cells via increasing proliferation; (3) if the ethylene signal is perceived, but not transduced (ein2-1), then cell differentiation takes place—the latter is enhanced by exogenous ABA while cell proliferation is reduced; (4) when the signal transduction pathway is constitutively active, the cells begin to exit the cell cycle and proceed to endo-reduplication (ctr1-1). In this case, the addition of exogenous ABA promotes reactivation of cell division. Full article
(This article belongs to the Section Plant Science)
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27 pages, 38043 KiB  
Article
Synthetic Biology for Terraformation Lessons from Mars, Earth, and the Microbiome
by Nuria Conde-Pueyo, Blai Vidiella, Josep Sardanyés, Miguel Berdugo, Fernando T. Maestre, Victor de Lorenzo and Ricard Solé
Life 2020, 10(2), 14; https://doi.org/10.3390/life10020014 - 9 Feb 2020
Cited by 29 | Viewed by 14200
Abstract
What is the potential for synthetic biology as a way of engineering, on a large scale, complex ecosystems? Can it be used to change endangered ecological communities and rescue them to prevent their collapse? What are the best strategies for such ecological engineering [...] Read more.
What is the potential for synthetic biology as a way of engineering, on a large scale, complex ecosystems? Can it be used to change endangered ecological communities and rescue them to prevent their collapse? What are the best strategies for such ecological engineering paths to succeed? Is it possible to create stable, diverse synthetic ecosystems capable of persisting in closed environments? Can synthetic communities be created to thrive on planets different from ours? These and other questions pervade major future developments within synthetic biology. The goal of engineering ecosystems is plagued with all kinds of technological, scientific and ethic problems. In this paper, we consider the requirements for terraformation, i.e., for changing a given environment to make it hospitable to some given class of life forms. Although the standard use of this term involved strategies for planetary terraformation, it has been recently suggested that this approach could be applied to a very different context: ecological communities within our own planet. As discussed here, this includes multiple scales, from the gut microbiome to the entire biosphere. Full article
(This article belongs to the Section Synthetic Biology and Systems Biology)
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12 pages, 1566 KiB  
Article
Endolithic Fungal Species Markers for Harshest Conditions in the McMurdo Dry Valleys, Antarctica
by Claudia Coleine, Nuttapon Pombubpa, Laura Zucconi, Silvano Onofri, Jason E. Stajich and Laura Selbmann
Life 2020, 10(2), 13; https://doi.org/10.3390/life10020013 - 6 Feb 2020
Cited by 17 | Viewed by 4994
Abstract
The microbial communities that inhabit lithic niches inside sandstone in the Antarctic McMurdo Dry Valleys of life’s limits on Earth. The cryptoendolithic communities survive in these ice-free areas that have the lowest temperatures on Earth coupled with strong thermal fluctuations, extreme aridity, oligotrophy [...] Read more.
The microbial communities that inhabit lithic niches inside sandstone in the Antarctic McMurdo Dry Valleys of life’s limits on Earth. The cryptoendolithic communities survive in these ice-free areas that have the lowest temperatures on Earth coupled with strong thermal fluctuations, extreme aridity, oligotrophy and high levels of solar and UV radiation. In this study, based on DNA metabarcoding, targeting the fungal Internal Transcribed Spacer region 1 (ITS1) and multivariate statistical analyses, we supply the first comprehensive overview onto the fungal diversity and composition of these communities sampled over a broad geographic area of the Antarctic hyper-arid cold desert. Six locations with surfaces that experience variable sun exposure were sampled to compare communities from a common area across a gradient of environmental pressure. The Operational Taxonomic Units (OTUs) identified were primarily members of the Ascomycota phylum, comprised mostly of the Lecanoromycetes and Dothideomycetes classes. The fungal species Friedmanniomyces endolithicus, endemic to Antarctica, was found to be a marker species to the harshest conditions occurring in the shady, south exposed rock surfaces. Analysis of community composition showed that sun exposure was an environmental property that explained community diversity and structured endolithic colonization. Full article
(This article belongs to the Collection What's on Board in the Journal Life)
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15 pages, 618 KiB  
Article
A Polyaddition Model for the Prebiotic Polymerization of RNA and RNA-Like Polymers
by Alex Spaeth and Mason Hargrave
Life 2020, 10(2), 12; https://doi.org/10.3390/life10020012 - 2 Feb 2020
Cited by 5 | Viewed by 5069
Abstract
Implicit in the RNA world hypothesis is that prebiotic RNA synthesis, despite occurring in an environment without biochemical catalysts, produced the long RNA polymers which are essential to the formation of life. In order to investigate the prebiotic formation of long RNA polymers, [...] Read more.
Implicit in the RNA world hypothesis is that prebiotic RNA synthesis, despite occurring in an environment without biochemical catalysts, produced the long RNA polymers which are essential to the formation of life. In order to investigate the prebiotic formation of long RNA polymers, we consider a general solution of functionally identical monomer units that are capable of bonding to form linear polymers by a step-growth process. Under the assumptions that (1) the solution is well-mixed and (2) bonding/unbonding rates are independent of polymerization state, the concentration of each length of polymer follows the geometric Flory-Schulz distribution. We consider the rate dynamics that produce this equilibrium; connect the rate dynamics, Gibbs free energy of bond formation, and the bonding probability; solve the dynamics in closed form for the representative special case of a Flory-Schulz initial condition; and demonstrate the effects of imposing a maximum polymer length. Afterwards, we derive a lower bound on the error introduced by truncation and compare this lower bound to the actual error found in our simulation. Finally, we suggest methods to connect these theoretical predictions to experimental results. Full article
(This article belongs to the Special Issue Themed Issue Commemorating Prof. David Deamer's 80th Birthday)
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12 pages, 4698 KiB  
Article
RNA Aptamers for a tRNA-Binding Protein from Aeropyrum pernix with Homologous Counterparts Distributed Throughout Evolution
by Senri Ohmori, Marina Wani, Saki Kitabatake, Yuka Nakatsugawa, Tadashi Ando, Takuya Umehara and Koji Tamura
Life 2020, 10(2), 11; https://doi.org/10.3390/life10020011 - 1 Feb 2020
Cited by 4 | Viewed by 3214
Abstract
In the present in vitro selection study, we isolated and characterized RNA aptamers for a tRNA-binding protein (Trbp) from an extremophile archaeon Aeropyrum pernix. Trbp-like structures are frequently found not only in aminoacyl-tRNA synthetases but also in diverse types of proteins from [...] Read more.
In the present in vitro selection study, we isolated and characterized RNA aptamers for a tRNA-binding protein (Trbp) from an extremophile archaeon Aeropyrum pernix. Trbp-like structures are frequently found not only in aminoacyl-tRNA synthetases but also in diverse types of proteins from different organisms. They likely arose early in evolution and have played important roles in evolution through interactions with key RNA structures. RNA aptamers specific for A. pernix Trbp were successfully selected from a pool of RNAs composed of 60 nucleotides, including a random 30-nucleotide region. From the secondary structures, we obtained a shortened sequence composed of 21 nucleotides, of which the 3′-terminal single stranded CA nucleotides are essential for binding. This may be related to the initial evolutionary role of the universal CCA-3′ terminus of tRNA in the interaction with Trbp-like structures. Full article
(This article belongs to the Section Proteins and Proteomics)
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7 pages, 578 KiB  
Article
Indexing Exoplanets with Physical Conditions Potentially Suitable for Rock-Dependent Extremophiles
by Madhu Kashyap Jagadeesh, Sagarika Rao Valluri, Vani Kari, Katarzyna Kubska and Łukasz Kaczmarek
Life 2020, 10(2), 10; https://doi.org/10.3390/life10020010 - 26 Jan 2020
Viewed by 4342
Abstract
The search for different life forms elsewhere in the universe is a fascinating area of research in astrophysics and astrobiology. Currently, according to the NASA Exoplanet Archive database, 3876 exoplanets have been discovered. The Earth Similarity Index (ESI) is defined as the geometric [...] Read more.
The search for different life forms elsewhere in the universe is a fascinating area of research in astrophysics and astrobiology. Currently, according to the NASA Exoplanet Archive database, 3876 exoplanets have been discovered. The Earth Similarity Index (ESI) is defined as the geometric mean of radius, density, escape velocity, and surface temperature and ranges from 0 (dissimilar to Earth) to 1 (similar to Earth). The ESI was created to index exoplanets on the basis of their similarity to Earth. In this paper, we examined rocky exoplanets whose physical conditions are potentially suitable for the survival of rock-dependent extremophiles, such as the cyanobacteria Chroococcidiopsis and the lichen Acarospora. The Rock Similarity Index (RSI) is first introduced and then applied to 1659 rocky exoplanets. The RSI represents a measure for Earth-like planets on which physical conditions are potentially suitable for rocky extremophiles that can survive in Earth-like extreme habitats (i.e., hot deserts and cold, frozen lands). Full article
(This article belongs to the Special Issue Planetary Exploration of Habitable Environments)
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15 pages, 2706 KiB  
Article
A Strategy for Combinatorial Cavity Design in De Novo Proteins
by Christina Karas and Michael Hecht
Life 2020, 10(2), 9; https://doi.org/10.3390/life10020009 - 23 Jan 2020
Cited by 10 | Viewed by 4475
Abstract
Protein sequence space is vast; nature uses only an infinitesimal fraction of possible sequences to sustain life. Are there solutions to biological problems other than those provided by nature? Can we create artificial proteins that sustain life? To investigate these questions, we have [...] Read more.
Protein sequence space is vast; nature uses only an infinitesimal fraction of possible sequences to sustain life. Are there solutions to biological problems other than those provided by nature? Can we create artificial proteins that sustain life? To investigate these questions, we have created combinatorial collections, or libraries, of novel sequences with no homology to those found in living organisms. Previously designed libraries contained numerous functional proteins. However, they often formed dynamic, rather than well-ordered structures, which complicated structural and mechanistic characterization. To address this challenge, we describe the development of new libraries based on the de novo protein S-824, a 4-helix bundle with a very stable 3-dimensional structure. Distinct from previous libraries, we targeted variability to a specific region of the protein, seeking to create potential functional sites. By characterizing variant proteins from this library, we demonstrate that the S-824 scaffold tolerates diverse amino acid substitutions in a putative cavity, including buried polar residues suitable for catalysis. We designed and created a DNA library encoding 1.7 × 106 unique protein sequences. This new library of stable de novo α-helical proteins is well suited for screens and selections for a range of functional activities in vitro and in vivo. Full article
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21 pages, 1113 KiB  
Article
A Theoretical Approach for the Electrochemical Characterization of Ciliary Epithelium
by Riccardo Sacco, Giovanna Guidoboni, Joseph W. Jerome, Giulio Bonifazi, Nicholas M. Marazzi, Alice C. Verticchio Vercellin, Matthew S. Lang and Alon Harris
Life 2020, 10(2), 8; https://doi.org/10.3390/life10020008 - 23 Jan 2020
Cited by 9 | Viewed by 8686
Abstract
The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion. Modulation of ionic secretion is a fundamental target for drug therapy in glaucoma, and therefore it is important to [...] Read more.
The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion. Modulation of ionic secretion is a fundamental target for drug therapy in glaucoma, and therefore it is important to identify the main factors contributing to it. As several ion transporters have been hypothesized as relevant players in CE physiology, we propose a theoretical approach to complement experimental methods in characterizing their role in the electrochemical and fluid-dynamical conditions of CE. As a first step, we compare two model configurations that differ by (i) types of transporters included for ion exchange across the epithelial membrane, and by (i) presence or absence of the intracellular production of carbonic acid mediated by the carbonic anhydrase enzyme. The proposed model configurations do not include neurohumoral mechanisms such as P2Y receptor-dependent, cAMP, or calcium-dependent pathways, which occur in the ciliary epithelium bilayer and influence the activity of ion transporters, pumps, and channels present in the cell membrane. Results suggest that one of the two configurations predicts sodium and potassium intracellular concentrations and transmembrane potential much more accurately than the other. Because of its quantitative prediction power, the proposed theoretical approach may help relate phenomena at the cellular scale, that cannot be accessed clinically, with phenomena occurring at the scale of the whole eye, for which clinical assessment is feasible. Full article
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41 pages, 4490 KiB  
Concept Paper
Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces
by Didier Auboeuf
Life 2020, 10(2), 7; https://doi.org/10.3390/life10020007 - 21 Jan 2020
Cited by 15 | Viewed by 7535
Abstract
The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made of [...] Read more.
The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made of complex multicellular organisms and, then, modified to fit a DNA-centric view. In this article, it is argued that based on a bottom-up approach starting from the physicochemical properties of nucleic and amino acid polymers, we should reject the facts that (i) natural selection plays a dominant role in evolution and (ii) the probability of mutations is independent of the generated phenotype. It is shown that the adaptation of a phenotype to an environment does not correspond to organism fitness, but rather corresponds to maintaining the genome stability and integrity. In a stable environment, the phenotype maintains the stability of its originating genome and both (genome and phenotype) are reproduced identically. In an unstable environment (i.e., corresponding to variations in physicochemical parameters above a physiological range), the phenotype no longer maintains the stability of its originating genome, but instead influences its variations. Indeed, environment- and cellular-dependent physicochemical parameters define the probability of mutations in terms of frequency, nature, and location in a genome. Evolution is non-deterministic because it relies on probabilistic physicochemical rules, and evolution is driven by a bidirectional interplay between genome and phenotype in which the phenotype ensures the stability of its originating genome in a cellular and environmental physicochemical parameter-depending manner. Full article
(This article belongs to the Section Evolutionary Biology)
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