scholarly journals The solubility product extends the buffering concept to heterotypic biomolecular condensates.

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Aniruddha Chattaraj ◽  
Michael L Blinov ◽  
Leslie M Loew
Keyword(s):  
Concentration Dependence ◽  
Solubility Product ◽  
Monomer Concentration ◽  
Coarse Grained ◽  
Wide Range ◽  
Particle Simulations ◽  
Large Clusters ◽  
Free Monomer ◽  
Liquid Liquid Phase Separation

Biomolecular condensates are formed by liquid-liquid phase separation (LLPS) of multivalent molecules. LLPS from a single ('homotypic') constituent is governed by buffering: above a threshold, free monomer concentration is clamped, with all added molecules entering the condensed phase. However, both experiment and theory demonstrate that buffering fails for the concentration dependence of multi-component ('heterotypic') LLPS. Using network-free stochastic modeling, we demonstrate that LLPS can be described by the solubility product constant (Ksp): the product of free monomer concentrations, accounting for the ideal stoichiometries governed by the valencies, displays a threshold above which additional monomers are funneled into large clusters; this reduces to simple buffering for homotypic systems. The Ksp regulates the composition of the dilute phase for a wide range of valencies and stoichiometries. The role of Ksp is further supported by coarse-grained spatial particle simulations. Thus, the solubility product offers a general formulation for the concentration dependence of LLPS.

scholarly journals Charge-Driven Condensation of RNA and Proteins Suggests Broad Role of Phase Separation in Cytoplasmic Environments

2020 ◽  
Author(s):  
Bercem Dutagaci ◽  
Grzegorz Nawrocki ◽  
Joyce Goodluck ◽  
Ali Akbar Ashkarran ◽  
Charles G. Hoogstraten ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Molecular Size ◽  
Liquid Phase Separation ◽  
Coarse Grained ◽  
Biological Macromolecules ◽  
Separation Processes ◽  
Cellular Environment ◽  
Liquid Liquid Phase Separation

ABSTRACTPhase separation processes are increasingly being recognized as important organizing mechanisms of biological macromolecules in cellular environments. Well established drivers of liquid-liquid phase separation are multi-valency and intrinsic disorder. Here, we show that globular macromolecules may condense simply based on electrostatic complementarity. More specifically, phase separation of mixtures between RNA and positively charged proteins is described from a combination of multiscale computer simulations with microscopy and spectroscopy experiments. Condensates retain liquid character and phase diagrams are mapped out as a function of molecular concentrations in experiment and as a function of molecular size and temperature via simulations. The results suggest a more general principle for phase separation that is based primarily on electrostatic complementarity without invoking polymer properties as in most previous studies. Simulation results furthermore suggest that such phase separation may occur widely in heterogenous cellular environment between nucleic acid and protein components.STATEMENT OF SIGNIFICANCELiquid-liquid phase separation has been recognized as a key mechanism for forming membrane-less organelles in cells. Commonly discussed mechanisms invoke a role of disordered peptides and specific multi-valent interactions. We report here phase separation of RNA and proteins based on a more universal principle of charge complementarity that does not require disorder or specific interactions. The findings are supported by coarse-grained simulations, theory, and experimental validation via microscopy and spectroscopy. The broad implication of this work is that condensate formation may be a universal phenomenon in biological systems.

scholarly journals Solubility product constant directs the formation of biomolecular condensates

2020 ◽  
Author(s):  
Aniruddha Chattaraj ◽  
Michael L. Blinov ◽  
Leslie M. Loew
Keyword(s):  
Phase Separation ◽  
Solubility Product ◽  
Cluster Formation ◽  
Cellular Structures ◽  
Stochastic Network ◽  
Physical Chemical ◽  
Solubility Product Constant ◽  
Concentration Threshold ◽  
Large Clusters ◽  
Liquid Liquid Phase Separation

AbstractBiomolecular condensates, formed by liquid-liquid phase separation (LLPS), are important cellular structures. Using stochastic network-free kinetic models, we establish a physical-chemical basis for the concentration threshold of heterotypic multivalent molecules required for LLPS. We associate phase separation with a bimodal partitioning of the cluster distribution into small oligomers vs. huge polymers. The simulations reveal that LLPS obeys the solubility product constant (Ksp): the product of monomer concentrations, accounting for ideal stoichiometries, does not exceed a threshold no matter how much additional monomer is added to the system – additional monomer is funneled into large clusters. The Ksp applies over a range of valencies and stoichiometries. However, consistent with the importance of disordered domains for LLPS, removing flexible linker domains funnels valency-matched monomers into a “dimer trap”, and Ksp no longer defines a threshold for large cluster formation. We propose Ksp as a new tool for elucidating biomolecular condensate biophysics.

scholarly journals Structure of biomolecular condensates from dissipative particle dynamics simulations

2019 ◽  
Author(s):  
Julian C. Shillcock ◽  
Maelick Brochut ◽  
Etienne Chénais ◽  
John H. Ipsen
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Intrinsically Disordered Proteins ◽  
Liquid Phase Separation ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Wide Range ◽  
End Caps ◽  
Liquid Liquid Phase Separation

ABSTRACTPhase separation of immiscible fluids is a common phenomenon in polymer chemistry, and is recognized as an important mechanism by which cells compartmentalize their biochemical reactions. Biomolecular condensates are condensed fluid droplets in cells that form by liquid-liquid phase separation of intrinsically-disordered proteins. They have a wide range of functions and are associated with chronic neurodegenerative diseases in which they become pathologically rigid. Intrinsically-disordered proteins are conformationally flexible and possess multiple, distributed binding sites for each other or for RNA. However, it remains unclear how their material properties depend on the molecular structure of the proteins. Here we use coarse-grained simulations to explore the phase behavior and structure of a model biomolecular condensate composed of semi-flexible polymers with attractive end-caps in a good solvent. Although highly simplified, the model contains the minimal molecular features that are sufficient to observe liquid-liquid phase separation of soluble polymers. The polymers condense into a porous, three-dimensional network in which their end-caps reversibly bind at junctions. The spatial separation of connected junctions scales with the polymer backbone length as a self-avoiding random walk over a wide range of concentration with a weak affinity-dependent prefactor. By contrast, the average number of polymers that meet at the junctions depends strongly on the end-cap affinity but only weakly on the polymer length. The regularity and porosity of the condensed network suggests a mechanism for cells to regulate biomolecular condensates. Interaction sites along a protein may be turned on or off to modulate the condensate’s porosity and tune the diffusion and interaction of additional proteins.

The role of turbulence strength on the acceleration of transrelativistic electrons

2020 ◽  
Author(s):  
Domenico Trotta ◽  
Luca Franci ◽  
David Burgess ◽  
Petr Hellinger ◽  
Joe Giacalone
Keyword(s):  
Dynamical Evolution ◽  
Electron Acceleration ◽  
Initial Energy ◽  
Turbulent Structures ◽  
Particle In Cell ◽  
Magnetic Structures ◽  
Physical Mechanisms ◽  
Wide Range ◽  
Particle Simulations

<p>Energetic particles are widely observed in many astrophysical systems, but the physical mechanisms responsible for their acceleration are not yet fully understood. We address the interaction of suprathermal, transrelativistic electrons with plasma turbulence at ion and sub-ion scales using a combination of hybrid particle-in-cell and test particle simulations. First, we present results of simulations with different turbulence amplitude. Two different mechanisms for electron energisation are identified: one is consistent with the picture of stochastic acceleration in turbulence, yielding to moderate electron energisation, while the other one involves electron trapping in turbulent structures, resulting in an efficient and fast electron energisation. The latter is observed to be active only for certain combinations of turbulence amplitude and electron initial energy. Furthermore, varying the injection scale, we explore the importance of the size of turbulent magnetic structures and of the nonlinear time associated to their dynamical evolution on electron acceleration. These results have important implications for electron acceleration in a wide range of space and astrophysical systems.</p>

scholarly journals Emergence of chromatin hierarchical loops from protein disorder and nucleosome asymmetry

2020 ◽  
Vol 117 (13) ◽  
pp. 7216-7224 ◽  
Author(s):  
Akshay Sridhar ◽  
Stephen E. Farr ◽  
Guillem Portella ◽  
Tamar Schlick ◽  
Modesto Orozco ◽  
...  
Keyword(s):  
Large Scale ◽  
Coarse Grained ◽  
Multiscale Approach ◽  
Protein Disorder ◽  
Wide Range ◽  
Chromatin Structural ◽  
Degree Of Condensation ◽  
Dynamics Simulations ◽  
Nucleosome Binding

Protein flexibility and disorder is emerging as a crucial modulator of chromatin structure. Histone tail disorder enables transient binding of different molecules to the nucleosomes, thereby promoting heterogeneous and dynamic internucleosome interactions and making possible recruitment of a wide-range of regulatory and remodeling proteins. On the basis of extensive multiscale modeling we reveal the importance of linker histone H1 protein disorder for chromatin hierarchical looping. Our multiscale approach bridges microsecond-long bias-exchange metadynamics molecular dynamics simulations of atomistic 211-bp nucleosomes with coarse-grained Monte Carlo simulations of 100-nucleosome systems. We show that the long C-terminal domain (CTD) of H1—a ubiquitous nucleosome-binding protein—remains disordered when bound to the nucleosome. Notably, such CTD disorder leads to an asymmetric and dynamical nucleosome conformation that promotes chromatin structural flexibility and establishes long-range hierarchical loops. Furthermore, the degree of condensation and flexibility of H1 can be fine-tuned, explaining chromosomal differences of interphase versus metaphase states that correspond to partial and hyperphosphorylated H1, respectively. This important role of H1 protein disorder in large-scale chromatin organization has a wide range of biological implications.

The Problem of Identifying and Modeling the Relationship between Monetary Factor and Inflation in the Russian Economy

2008 ◽  
pp. 61-76
Author(s):  
A. Porshakov ◽  
A. Ponomarenko
Keyword(s):  
Money Supply ◽  
Money Demand ◽  
Russian Economy ◽  
Long Run ◽  
Complex Approach ◽  
Wide Range ◽  
Long Time ◽  
The Relationship ◽  
Supply Side Factors

The role of monetary factor in generating inflationary processes in Russia has stimulated various debates in social and scientific circles for a relatively long time. The authors show that identification of the specificity of relationship between money and inflation requires a complex approach based on statistical modeling and involving a wide range of indicators relevant for the price changes in the economy. As a result a model of inflation for Russia implying the decomposition of inflation dynamics into demand-side and supply-side factors is suggested. The main conclusion drawn is that during the recent years the volume of inflationary pressures in the Russian economy has been determined by the deviation of money supply from money demand, rather than by money supply alone. At the same time, monetary factor has a long-run spread over time impact on inflation.

Patterns in diversity and composition of the microbenthos of subarctic intertidal beaches with different morphodynamics

2020 ◽  
Vol 648 ◽  
pp. 19-38
Author(s):  
AI Azovsky ◽  
YA Mazei ◽  
MA Saburova ◽  
PV Sapozhnikov
Keyword(s):  
Species Abundance ◽  
Abundance Ratio ◽  
Wave Action ◽  
Coarse Grained ◽  
Sediment Properties ◽  
Β Diversity ◽  
Α Diversity ◽  
Wide Range ◽  
Similar Mode ◽  
Abundance And Diversity

Diversity and composition of benthic diatom algae and ciliates were studied at several beaches along the White and Barents seas: from highly exposed, reflective beaches with coarse-grained sands to sheltered, dissipative silty-sandy flats. For diatoms, the epipelic to epipsammic species abundance ratio was significantly correlated with the beach index and mean particle size, while neither α-diversity measures nor mean cell length were related to beach properties. In contrast, most of the characteristics of ciliate assemblages (diversity, total abundance and biomass, mean individual weight and percentage of karyorelictids) demonstrated a strong correlation to beach properties, remaining low at exposed beaches but increasing sharply in more sheltered conditions. β-diversity did not correlate with beach properties for either diatoms or ciliates. We suggest that wave action and sediment properties are the main drivers controlling the diversity and composition of the intertidal microbenthos. Diatoms and ciliates, however, demonstrated divergent response to these factors. Epipelic and epipsammic diatoms exhibited 2 different strategies to adapt to their environments and therefore were complementarily distributed along the environmental gradient and compensated for each other in diversity. Most ciliates demonstrated a similar mode of habitat selection but differed in their degree of tolerance. Euryporal (including mesoporal) species were relatively tolerant to wave action and therefore occurred under a wide range of beach conditions, though their abundance and diversity were highest in fine, relatively stable sediments on sheltered beaches, whereas the specific interstitial (i.e. genuine microporal) species were mostly restricted to only these habitats.

Introduction: Emotion, History and the Arts

2018 ◽  
Vol 7 (2) ◽  
pp. 117-128 ◽  
Author(s):  
Erin Sullivan ◽  
Marie Louise Herzfeld-Schild
Keyword(s):  
Historical Change ◽  
Carson Mccullers ◽  
Emotional Life ◽  
Review Section ◽  
The Arts ◽  
Wide Range ◽  
War Correspondents ◽  
History Of ◽  
Johan Huizinga

This introduction surveys the rise of the history of emotions as a field and the role of the arts in such developments. Reflecting on the foundational role of the arts in the early emotion-oriented histories of Johan Huizinga and Jacob Burkhardt, as well as the concerns about methodological impressionism that have sometimes arisen in response to such studies, the introduction considers how intensive engagements with the arts can open up new insights into past emotions while still being historically and theoretically rigorous. Drawing on a wide range of emotionally charged art works from different times and places—including the novels of Carson McCullers and Harriet Beecher-Stowe, the private poetry of neo-Confucian Chinese civil servants, the photojournalism of twentieth-century war correspondents, and music from Igor Stravinsky to the Beatles—the introduction proposes five ways in which art in all its forms contributes to emotional life and consequently to emotional histories: first, by incubating deep emotional experiences that contribute to formations of identity; second, by acting as a place for the expression of private or deviant emotions; third, by functioning as a barometer of wider cultural and attitudinal change; fourth, by serving as an engine of momentous historical change; and fifth, by working as a tool for emotional connection across communities, both within specific time periods but also across them. The introduction finishes by outlining how the special issue's five articles and review section address each of these categories, while also illustrating new methodological possibilities for the field.

Short Films from a Small Nation

2018 ◽  
Author(s):  
C. Claire Thomson
Keyword(s):  
Public Information ◽  
Industrial Process ◽  
Actor Network Theory ◽  
Documentary Films ◽  
Wide Range ◽  
Short Films ◽  
Post War ◽  
The 1960S ◽  
Art And Architecture

The first book-length study in English of a national corpus of state-sponsored informational film, this book traces how Danish shorts on topics including social welfare, industry, art and architecture were commissioned, funded, produced and reviewed from the inter-war period to the 1960s. For three decades, state-sponsored short filmmaking educated Danish citizens, promoted Denmark to the world, and shaped the careers of renowned directors like Carl Th. Dreyer. Examining the life cycle of a representative selection of films, and discussing their preservation and mediation in the digital age, this book presents a detailed case study of how informational cinema is shaped by, and indeed shapes, its cultural, political and technological contexts.The book combines close textual analysis of a broad range of films with detailed accounts of their commissioning, production, distribution and reception in Denmark and abroad, drawing on Actor-Network Theory to emphasise the role of a wide range of entities in these processes. It considers a broad range of genres and sub-genres, including industrial process films, public information films, art films, the city symphony, the essay film, and many more. It also maps international networks of informational and documentary films in the post-war period, and explores the role of informational film in Danish cultural and political history.

Quantitative and Qualitative Methods of Studying the Processes of Socialization of a Modern Teenager

2020 ◽  
pp. 102-109
Author(s):  
Svetlana Alekseevna Raschetina ◽  
Keyword(s):  
Research Methods ◽  
Interpersonal Relations ◽  
Internet Communication ◽  
Socialization Process ◽  
Wide Range ◽  
The Family ◽  
Modern Family ◽  
Making Friends ◽  
Main Support

Relevance and problem statement. Modern unstable society is characterized by narrowing the boundaries of controlled socialization and expanding the boundaries of spontaneous socialization of a teenager based on his immersion in the question arises about the importance of the family in the process of socialization of a teenager in the conditions of expanding the space of socialization. There is a need to study the role of the family in this process, to search, develop and test research methods that allow us to reveal the phenomenon of socialization from the side of its value characteristics. The purpose and methodology of the study: to identify the possibilities of a systematic and anthropological methodology for studying the role of the family in the process of socialization of adolescents in modern conditions, testing research methods: photo research on the topic “Ego – I” (author of the German sociologist H. Abels), profile update reflexive processes (by S. A. Raschetina). Materials and results of the study. The study showed that for all the problems that exist in the family of the perestroika era and in the modern family, it acts for a teenager as a value and the first (main) support in the processes of socialization. The positions well known in psychology about the importance of interpersonal relations in adolescence for the formation of attitudes towards oneself as the basis of socialization are confirmed. Today, the frontiers of making friends have expanded enormously on the basis of Internet communication. The types of activities of interest to a teenager (traditional and new ones related to digitalization) are the third pillar of socialization. Conclusion. The “Ego – I” method of photo research has a wide range of possibilities for quantitative and qualitative analysis of the socialization process to identify the value Pillars of this process.

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