The Central Symbiosis of Molecular Biology: Molecules in Mutualism.

As illustrated by the mitochondrion and the eukaryotic cell, little in biology makes sense except in light of mutualism. Mutualisms are persistent, intimate, and reciprocal exchanges; an organism proficient in obtaining certain benefits confers those on a partner, which reciprocates by conferring different benefits. Mutualisms (i) increase fitness, (ii) inspire robustness, (iii) are resilient and resistant to change, (iv) sponsor co-evolution, (v) foster innovation, and (vi) involve partners that are distantly related with contrasting yet complementary proficiencies. Previous to this work, mutualisms were understood to operate on levels of cells, organisms, ecosystems, and even societies and economies. Here, the concepts of mutualism are extended to molecules and are seen to apply to the relationship between RNA and protein. Polynucleotide and polypeptide are Molecules in Mutualism. RNA synthesizes protein in the ribosome and protein synthesizes RNA in polymerases. RNA and protein are codependent, and trade proficiencies. Protein has proficiency in folding into complex three-dimensional states, contributing enzymes, fibers, adhesives, pumps, pores, switches, and receptors. RNA has proficiency in direct molecular recognition, achieved by complementary base pairing interactions, which allow it to maintain, record, and transduce information. The large phylogenetic distance that characterizes partnerships in organismal mutualism has close analogy with large distance in chemical space between RNA and protein. The RNA backbone is anionic and self-repulsive and cannot form hydrophobic structural cores. The protein backbone is neutral and cohesive and commonly forms hydrophobic cores. Molecules in Mutualism extends beyond RNA and protein. A cell is a consortium of molecules in which nucleic acids, proteins, polysaccharides, phospholipids, and other molecules form a mutualism consortium that drives metabolism and replication. Analogies are found in systems such as stromatolites, which are large consortia of symbiotic organisms. It seems reasonable to suggest that 'polymers in mutualism relationships' is a useful and predictive definition of life

Quantum noise limited interferometric measurement of atomic noise: towards spin squeezing on the Cs clock transition

We investigate theoretically and experimentally a nondestructive interferometric measurement of the state population of an ensemble of laser cooled and trapped atoms. This study is a step towards generation of (pseudo-) spin squeezing of cold atoms targeted at the improvement of the Caesium clock performance beyond the limit set by the quantum projection noise of atoms. We calculate the phase shift and the quantum noise of a near resonant optical probe pulse propagating through a cloud of cold 133Cs atoms. We analyze the figure of merit for a quantum non-demolition (QND) measurement of the collective pseudo-spin and show that it can be expressed simply as a product of the ensemble optical density and the pulse integrated rate of the spontaneous emission caused by the off-resonant probe light. Based on this, we propose a protocol for the sequence of operations required to generate and utilize spin squeezing for the improved atomic clock performance via a QND measurement on the probe light. In the experimental part we demonstrate that the interferometric measurement of the atomic population can reach the sensitivity of the order of N_at^1/2 in a cloud of N_at cold atoms, which is an important benchmark towards the experimental realisation of the theoretically analyzed protocol.Comment: 12 pages and 9 figures, accepted to Physical Review

Multiple prebiotic metals mediate translation.

Today, Mg2+ is an essential cofactor with diverse structural and functional roles in life's oldest macromolecular machine, the translation system. We tested whether ancient Earth conditions (low O2, high Fe2+, and high Mn2+) can revert the ribosome to a functional ancestral state. First, SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) was used to compare the effect of Mg2+, Fe2+, and Mn2+ on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe2+ or Mn2+ could mediate protein production, and quantified ribosomal metal content. We found that (i) Mg2+, Fe2+, and Mn2+ had strikingly similar effects on rRNA folding; (ii) Fe2+ and Mn2+ can replace Mg2+ as the dominant divalent cation during translation of mRNA to functional protein; and (iii) Fe and Mn associate extensively with the ribosome. Given that the translation system originated and matured when Fe2+ and Mn2+ were abundant, these findings suggest that Fe2+ and Mn2+ played a role in early ribosomal evolution

Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions.

Numerous long-standing questions in origins-of-life research center on the history of biopolymers. For example, how and why did nature select the polypeptide backbone and proteinaceous side chains? Depsipeptides, containing both ester and amide linkages, have been proposed as ancestors of polypeptides. In this paper, we investigate cationic depsipeptides that form under mild dry-down reactions. We compare the oligomerization of various cationic amino acids, including the cationic proteinaceous amino acids (lysine, Lys; arginine, Arg; and histidine, His), along with nonproteinaceous analogs of Lys harboring fewer methylene groups in their side chains. These analogs, which have been discussed as potential prebiotic alternatives to Lys, are ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid (Orn, Dab, and Dpr). We observe that the proteinaceous amino acids condense more extensively than these nonproteinaceous amino acids. Orn and Dab readily cyclize into lactams, while Dab and Dpr condense less efficiently. Furthermore, the proteinaceous amino acids exhibit more selective oligomerization through their α-amines relative to their side-chain groups. This selectivity results in predominantly linear depsipeptides in which the amino acids are α-amine-linked, analogous to today's proteins. These results suggest a chemical basis for the selection of Lys, Arg, and His over other cationic amino acids for incorporation into proto-proteins on the early Earth. Given that electrostatics are key elements of protein-RNA and protein-DNA interactions in extant life, we hypothesize that cationic side chains incorporated into proto-peptides, as reported in this study, served in a variety of functions with ancestral nucleic acid polymers in the early stages of life

Application of Terahertz Pulse Time-Domain Holography for Phase Imaging

Terahertz pulse time-domain holography (THz PTDH) is the powerful technique for high-resolution amplitude and phase THz imaging that allows mapping spectroscopic information across the imaged object. In this paper, we consider most sought after applications of phase imaging provided by this technique and experimentally demonstrate the ability of the method to reconstruct smooth and stepped relief features of an object that is transparent in THz region. Unlike the amplitude distribution, which does not contain any significant information in this case, phase distribution not only reveals the object qualitatively,but also allows the reconstruction of the object thicknessespattern, even in low signal-to-noise registration conditions. Mainlimitations of the proposed method, such as transverse resolutionand low signal-to-noise environment are carefully studied and mitigated

Comprehensive survey and geometric classification of base triples in RNA structures

Base triples are recurrent clusters of three RNA nucleobases interacting edge-to-edge by hydrogen bonding. We find that the central base in almost all triples forms base pairs with the other two bases of the triple, providing a natural way to geometrically classify base triples. Given 12 geometric base pair families defined by the Leontis–Westhof nomenclature, combinatoric enumeration predicts 108 potential geometric base triple families. We searched representative atomic-resolution RNA 3D structures and found instances of 68 of the 108 predicted base triple families. Model building suggests that some of the remaining 40 families may be unlikely to form for steric reasons. We developed an on-line resource that provides exemplars of all base triples observed in the structure database and models for unobserved, predicted triples, grouped by triple family, as well as by three-base combination (http://rna.bgsu.edu/Triples). The classification helps to identify recurrent triple motifs that can substitute for each other while conserving RNA 3D structure, with applications in RNA 3D structure prediction and analysis of RNA sequence evolution

Cryo-EM structure and rRNA modification sites of a plant ribosome

[EN] Protein synthesis in crop plants contributes to the balance of food and fuel on our planet, which influences human metabolic activity and lifespan. Protein synthesis can be regulated with respect to changing environmental cues via the deposition of chemical modifications into rRNA. Here, we present the structure of a plant ribosome from tomato and a quantitative mass spectrometry analysis of its rRNAs. The study reveals fine features of the ribosomal proteins and 71 plant-specific rRNA modifications, and it re-annotates 30 rRNA residues in the available sequence. At the protein level, isoAsp is found in position 137 of uS11, and a zinc finger previously believed to be universal is missing from eL34, suggesting a lower effect of zinc deficiency on protein synthesis in plants. At the rRNA level, the plant ribosome differs markedly from its human counterpart with respect to the spatial distribution of modifications. Thus, it represents an additional layer of gene expression regulation, highlighting the molecular signature of a plant ribosome. The results provide a reference model of a plant ribosome for structural studies and an accurate marker for molecular ecology.This work was supported by the Swedish Foundation for Strategic Research (ARC19:0051), the Knut and Alice Wallenberg Foundation (2018.0080), the EMBO Young Investigator Program, and a NASA award (80NSSC18K1139 to A.S.P.).Cottilli, P.; Itoh, Y.; Nobe, Y.; Petrov, AS.; Lisón, P.; Taoka, M.; Amunts, A. (2022). Cryo-EM structure and rRNA modification sites of a plant ribosome. Plant communications. 3(5):1-9. https://doi.org/10.1016/j.xplc.2022.100342193

On the local structure of Lorentzian Einstein manifolds with parallel distribution of null lines

We study transformations of coordinates on a Lorentzian Einstein manifold with a parallel distribution of null lines and show that the general Walker coordinates can be simplified. In these coordinates, the full Lorentzian Einstein equation is reduced to equations on a family of Einstein Riemannian metrics.Comment: Dedicated to Dmitri Vladimirovich Alekseevsky on his 70th birthda

Changing Vectors of International Cooperation of Russian Universities in the New Geopolitical Situation

Introduction. With the implementation of state policy aimed at integrating the Russian higher education into the world educational system, universities internationalization has been intensively developing in recent decades. However, the unprecedented sanction pressure of unfriendly countries (starting in 2022) affected universities international activity prompting them to search for new foreign partners. The purpose of the research was to study the vectors of Russian universities’ international activity under transformation in the current geopolitical situation. The analysis of new geography and forms of international cooperation in the educational, scientific, cultural and humanitarian spheres was of specific interest. Materials and Methods. The method of content analysis was employed to study the news on international activity, posted on the websites of leading Russian universities, government authorities and specialized organizations. The results of this analysis were mapped (the mapping method was used). The method of substantive analysis of news reports was used to obtain a characterization of the forms of international cooperation. Statistical data were analyzed in the article by means of quantitative methods. The methods of substantive analysis, systematization and classification of information contained in theoretical sources, normative-legal acts, information and analytical materials were used. Results. A set of sanction restrictions on the internationalization of Russian universities is characterized. Diagrammatic maps of the new geography of their international cooperation are presented. They indicate the growth of international contacts with universities in the CIS countries, Asia, Africa and Latin America against the backdrop of the decreased contacts with Western countries. Discussion and Conclusion. The expansion of international cooperation between Russian universities geography can help minimize risks of sanction pressure, as well as open up new opportunities for the long-term international partnership development and the formation of new world scientific and educational superiority centers. The article can be useful for universities in Russia for forming their international strategy in the new geopolitical conditions

RNAcentral 2021: secondary structure integration, improved sequence search and new member databases

RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences that provides a single access point to 44 RNA resources and >18 million ncRNA sequences from a wide range of organisms and RNA types. RNAcentral now also includes secondary (2D) structure information for >13 million sequences, making RNAcentral the world's largest RNA 2D structure database. The 2D diagrams are displayed using R2DT, a new 2D structure visualization method that uses consistent, reproducible and recognizable layouts for related RNAs. The sequence similarity search has been updated with a faster interface featuring facets for filtering search results by RNA type, organism, source database or any keyword. This sequence search tool is available as a reusable web component, and has been integrated into several RNAcentral member databases, including Rfam, miRBase and snoDB. To allow for a more fine-grained assignment of RNA types and subtypes, all RNAcentral sequences have been annotated with Sequence Ontology terms. The RNAcentral database continues to grow and provide a central data resource for the RNA community