Phase separation underlies the formation of biomolecular condensates. We hypothesize the cellular processes that occur within condensates shape their structural features. We use the example of transcription to discuss structure–function relationships in condensates. Various types of transcriptional condensates have been reported across the evolutionary spectrum in the cell nucleus as well as in mitochondrial and bacterial nucleoids. In vitro and in vivo observations suggest that transcriptional activity of condensates influences their supramolecular structure, which in (...) turn affects their function. Condensate organization thus becomes driven by differences in miscibility among the DNA and proteins of the transcription machinery and the RNA transcripts they generate. These considerations are in line with the notion that cellular processes shape the structural properties of condensates, leading to a dynamic, mutual interplay between structure and function in the cell. (shrink)

Cis‐regulatory elements govern gene expression programs to determine cell identity during development. Recently, the possibility that multiple enhancers are orchestrated in clusters of enhancers has been suggested. How these elements are arranged in the 3D space to control the activation of a specific promoter remains unclear. Our recent work revealed that the TGFβ pathway drives the assembly of enhancer clusters and precise gene activation during neurogenesis. We discovered that the TGFβ pathway coactivator JMJD3 was essential in maintaining these structures in (...) the 3D space. To do that, JMJD3 required an intrinsically disordered region involved in forming phase‐separated biomolecular condensates found in the enhancer clusters. Our data support the existence of a relationship between 3D‐conformation of the chromatin, biomolecular condensates, and TGFβ‐driven response during mammalian neurogenesis. In this review, we discuss how signaling (TGFβ), epigenetics (JMJD3), and biochemical properties (biomolecular condensates nucleation) are coordinated to modulate the genome structure to guarantee proper neural development. Moreover, we comment on the potential underlying mechanisms and implications of the enhancer‐mediated regulation. Finally, we point out the knowledge gaps that still need to be addressed. (shrink)

Cells contain a myriad of membraneless ribonucleoprotein (RNP) condensates with distinct compositions of proteins and RNAs. RNP condensates participate in different cellular activities, including RNA storage, mRNA translation or decay, stress response, etc. RNP condensates are assembled via liquid‐liquid phase separation (LLPS) driven by multivalent interactions. Transition of RNP condensates into bodies with abnormal material properties, such as solid‐like amyloid structures, is associated with the pathogenesis of various diseases. In this review, we focus on how RNAs (...) regulate multiple aspects of RNP condensates, such as dynamic assembly and/or disassembly and biophysical properties. RNA properties – including concentration, sequence, length and structure – also determine the phase behaviors of RNP condensates. RNA is also involved in specifying autophagic degradation of RNP condensates. Unraveling the role of RNA in RNPs provides novel insights into pathological accumulation of RNPs in various diseases. This new understanding can potentially be harnessed to develop therapeutic strategies. (shrink)

Liquid‐liquid phase separation (LLPS) has recently emerged as a possible mechanism that enables ubiquitin‐binding shuttle proteins to facilitate the degradation of ubiquitinated substrates via distinct protein quality control (PQC) pathways. Shuttle protein LLPS is modulated by multivalent interactions among their various domains as well as heterotypic interactions with polyubiquitin chains. Here, the properties of three different shuttle proteins (hHR23B, p62, and UBQLN2) are closely examined, unifying principles for the molecular determinants of their LLPS are identified, and how LLPS is connected (...) to their functions is discussed. Evidence supporting LLPS of other shuttle proteins is also found. In this review, it is proposed that shuttle protein LLPS leads to spatiotemporal regulation of PQC activities by mediating the recruitment of PQC machinery (including proteasomes or autophagic components) to biomolecular condensates, assembly/disassembly of condensates, selective enrichment of client proteins, and extraction of ubiquitinated proteins from condensates in cells. (shrink)

Cytoplasmic messenger ribonucleoprotein particles (mRNPs) represent the cellular transcriptome, and recent data have challenged our current understanding of their architecture, transport, and complexity before translation. Pre‐translational mRNPs are composed of a single transcript, whereas P‐bodies and stress granules are condensates. Both pre‐translational mRNPs and actively translating mRNPs seem to adopt a linear rather than a closed‐loop configuration. Moreover, assembly of pre‐translational mRNPs in physical RNA regulons is an unlikely event, and co‐regulated translation may occur locally following extracellular cues. We (...) envisage a stochastic mRNP transport mechanism where translational repression of single mRNPs—in combination with microtubule‐mediated cytoplasmic streaming and docking events—are prerequisites for local translation, rather than direct transport. (shrink)

Over the past decade, research has revealed biomolecular condensates' relevance in diverse cellular functions. Through a phase separation process, they concentrate macromolecules in subcompartments shaping the cellular organization and physiology. In the nucleus, biomolecular condensates assemble relevant biomolecules that orchestrate gene expression. We here hypothesize that chromatin condensates can also modulate the nongenetic functions of the genome, including the nuclear mechanical properties. The importance of chromatin condensates is supported by the genetic evidence indicating that (...) mutations in their members are causative of a group of rare Mendelian diseases named chromatinopathies (CPs). Despite a broad spectrum of clinical features and the perturbations of the epigenetic machinery characterizing the CPs, recent findings highlighted negligible changes in gene expression. These data argue in favor of possible noncanonical functions of chromatin condensates in regulating the genome's spatial organization and, consequently, the nuclear mechanics. In this review, we discuss how condensates may impact nuclear mechanical properties, thus affecting the cellular response to mechanical cues and, eventually, cell fate and identity.Chromatin condensates organize macromolecules in the nucleus orchestrating the transcription regulation and mutations in their members are responsible for rare diseases named chromatinopathies. We argue that chromatin condensates, in concert with the nuclear lamina, may also govern the nuclear mechanical properties affecting the cellular response to external cues. (shrink)

With decades of research seeking to generalize sterile alpha motif (SAM) biology, many outstanding questions remain regarding this multi‐tool protein module. Recent data from structural and molecular/cell biology has begun to reveal new SAM modes of action in cell signaling cascades and biomolecular condensation. SAM‐dependent mechanisms underlie blood‐related (hematologic) diseases, including myelodysplastic syndromes and leukemias, prompting our focus on hematopoiesis for this review. With the increasing coverage of SAM‐dependent interactomes, a hypothesis emerges that SAM interaction partners and binding affinities (...) work to fine tune cell signaling cascades in developmental and disease contexts, including hematopoiesis and hematologic disease. This review discusses what is known and remains unknown about the standard mechanisms and neoplastic properties of SAM domains and what the future might hold for developing SAM‐targeted therapies. (shrink)

The intracellular multiprotein complex β‐catenin destruction complex plays a key role in Wnt/β‐catenin signaling. Wnt stimulation induces the assembly of the receptor‐associated signalosome and the inactivation of the destruction complex, leading to β‐catenin accumulation and transcriptional activation of the target genes. The core components of the destruction complex include Axin, APC, GSK3β, CK1α and other proteins. Recent studies demonstrated that Axin and APC undergo liquid–liquid phase separation (LLPS), which is critical for their function to regulate Wnt/β‐catenin signaling. Here, we discuss (...) the possible roles of LLPS in Wnt/β‐catenin signaling and regulation of Axin LLPS by post‐translational modifications. (shrink)

As an explanation for order and long range correlations in living systems, Fröhlich (1968; 1970; 1975) proposed certain biomolecules pumped by metabolic processes could exhibit coherent phonon dynamics, perhaps even macroscopic quantum coherence akin to Bose Einstein condensation or lasers. The biomolecular requirements, according to Fröhlich, were: 1) a geometric array or lattice of dipoles constrained in a common voltage gradient, and 2) ample, non coherent biochemical energy. Eligible proposed candidates included membrane proteins, nucleic acids and cytoskeletal microtubules.

The defining principle of evolutionary biology is that all species, extant and extinct, evolved from ancient prokaryotic cells. Their initial appearance and adaptive evolution are proposed to have been accompanied by a cellular sentience, by feelings, subjectivity or, in a word, 'consciousness'. Prokaryotic cells, such as archaea and bacteria, have natural unitary, valence-marked 'mental' representations. They process and evaluate sensory information in a context-dependent manner. They learn, establish memories, and communicate using biophysical fields acting on excitable membranes. Symbiotic eukaryotic cells, (...) which evolved much later, initiated a compound cellular subjectivity utilizing 'senomic' and 'ephaptic' principles that evolved into the varieties of consciousness seen in multicellular species. This Cellular Basis of Consciousness (CBC) model provides a novel framework within which to approach fundamental issues such as the origins of life and the emergence of mind. (shrink)

The concept of „fundamental unity of life" belongs to the descriptive element of biology. It contrasts with the equally empirical concept of multiplicity and diversity of living forms. „Fundamental unity of life" means that however peculiar a biological form might be, some of its essential mechanisms are exactly the same as in the rest of the biological world. It is astonishing to realize that so different beings as bacteria, plants and men manifest several evidently non fortuitous identities. For thousands of (...) years man has been aware, that many behavioral traits are common to all living beings. Every living being processes matter, multiplies, regenerates, adapts to its surroundings'. During the last century a new, impressive confirmation and amplification of these resemblances was found on the molecular and subcellular level. One may say that the previous, rather raw concepts of nutrition, reproduction, adaptation and regeneration have been replaced by the more or less direct evidence, observable within the single living cells. So the idea of „fundamental unity of life" underwent a legitimate „reduction" to the level of biochemistry. (shrink)

The concept of „fundamental unity of life" belongs to the descriptive element of biology. It contrasts with the equally empirical concept of multiplicity and diversity of living forms. „Fundamental unity of life" means that however peculiar a biological form might be, some of its essential mechanisms are exactly the same as in the rest of the biological world. It is astonishing to realize that so different beings as bacteria, plants and men manifest several evidently non fortuitous identities. For thousands of (...) years man has been aware, that many behavioral traits are common to all living beings. Every living being processes matter, multiplies, regenerates, adapts to its surroundings'. During the last century a new, impressive confirmation and amplification of these resemblances was found on the molecular and subcellular level. One may say that the previous, rather raw concepts of nutrition, reproduction, adaptation and regeneration have been replaced by the more or less direct evidence, observable within the single living cells. So the idea of „fundamental unity of life" underwent a legitimate „reduction" to the level of biochemistry. (shrink)

This essay considers the prospects of modeling spacetime as a phenomenon that emerges in the low-energy limit of a quantum liquid. It evaluates three examples of spacetime analogues in condensed matter systems that have appeared in the recent physics literature, indicating the extent to which they are viable, and considers what they suggest about the nature of spacetime.

A model \ of ZF is said to be condensable if \\prec _{\mathbb {L}_{{\mathcal {M}}}} {\mathcal {M}}\) for some “ordinal” \, where \:=,\in )^{{\mathcal {M}}}\) and \ is the set of formulae of the infinitary logic \ that appear in the well-founded part of \. The work of Barwise and Schlipf in the 1970s revealed the fact that every countable recursively saturated model of ZF is cofinally condensable \prec _{\mathbb {L}_{{\mathcal {M}}}}{\mathcal {M}}\) for an unbounded collection of \). Moreover, it (...) can be readily shown that any \-nonstandard condensable model of \ is recursively saturated. These considerations provide the context for the following result that answers a question posed to the author by Paul Kindvall Gorbow.Theorem A. Assuming a modest set-theoretic hypothesis, there is a countable model \ of ZFC that is both definably well-founded is in the well-founded part of \}\) and cofinally condensable. We also provide various equivalents of the notion of condensability, including the result below.Theorem B. The following are equivalent for a countable model \ of \: \ is condensable. \ is cofinally condensable. \ is nonstandard and \\prec _{\mathbb {L}_{{\mathcal {M}}}}{\mathcal {M}}\) for an unbounded collection of \. (shrink)

Condensed detachment is usually regarded as a notation, and defined by example. In this paper it is regarded as a rule of inference, and rigorously defined with the help of the Unification Theorem of J. A. Robinson. Historically, however, the invention of condensed detachment by C. A. Meredith preceded Robinson's studies of unification. It is argued that Meredith's ideas deserve recognition in the history of unification, and the possibility that Meredith was influenced, through ukasiewicz, by ideas of Tarski going back (...) at least to 1939, and possibly to 1930 or earlier, is discussed. It is proved that a term is derivable by substitution and ordinary detachment from given axioms if and only if it is a substitution instance of a term which is derivable from these axioms by condensed detachment, and it is shown how this theorem enables the ideas of ukasiewicz and Tarski mentioned above to be formalized and extended. Finally, it is shown how condensed detachment may be subsumed within the resolution principle of J. A. Robinson, and several computer studies of particular Hilbert-type propositional calculi using programs based on condensed detachment or on resolution are briefly discussed. (shrink)

We address anticipated fermion–antifermion and dimension-4 gauge-field vacuum-condensate contributions to the magnetic portion of the fermion–photon vertex function in the presence of a vacuum with nonperturbative content, such as that of QCD. We discuss how inclusion of such condensate contributions may lead to a vanishing anomalous magnetic moment, in which case vacuum condensates may account for the apparent consistency between constituent quark masses characterizing baryon magnetic moments and those characterizing baryon spectroscopy.

The belief in the Darwinian theory of evolution appeared to be shaken when one tried to interpret statements of molecular biology in it. As a consequence there arose a theory of non-Darwinian neutral evolution. The supporters of this theory believe that under natural conditions no factors exist which can distinguish and select organisms on their internal (molecular) structure. In the opinion of these neutralists natural selection cannot in principle control the molecular constitution of organisms. Contrary to the viewpoint of the (...) critics of neutralism it is impossible to admit that nucleic acids, proteins and other biomolecules can evolve without the participation of natural selection. This controversy in contemporary theoretical biology can be solved by integrating the conceptions of molecular ecology with Darwinian theory. Molecular ecology acknowledges the interactions of organisms by means of chemical substances synthesized by them. Such chemical ecological factors play a leading part in the selective stages of biomolecular evolution. These diverse chemical ecological interrelations take place intensively when living beings interact with parasitic microbes. (shrink)

It is widely hoped that quantum gravity will shed light on the question of the origin of time in physics. The currently dominant approaches to a candidate quantum theory of gravity have naturally evolved from general relativity, on the one hand, and from particle physics, on the other hand. A third important branch of twentieth century ‘fundamental’ physics, condensed-matter physics, also offers an interesting perspective on quantum gravity, and thereby on the problem of time. The bottomline might sound disappointing: to (...) understand the origin of time, much more experimental input is needed than what is available today. Moreover it is far from obvious that we will ever find out the true origin of physical time, even if we become able to directly probe physics at the Planck scale. But we might learn some interesting lessons about time and the structure of our universe in the process. A first lesson is that there are probably several characteristic scales associated with “quantum gravity” effects, rather than the single Planck scale usually considered. These can differ by several orders of magnitude, and thereby conspire to hide certain effects expected from quantum gravity, rendering them undetectable even with Planck-scale experiments. A more tentative conclusion is that the hierarchy between general relativity, special relativity and Newtonian physics, usually taken for granted, might have to be interpreted with caution. (shrink)

In this essay, I consider what condensed matter physics has to say about the nature of spacetime. In particular, I consider the extent to which spacetime can be modeled as a quantum liquid, with matter and force fields described by effective field theories of the low-energy excitations of the liquid. After a brief review of effective field theories in 2-dim highly-correlated condensed matter systems, I evaluate analogies in the recent physics literature between spacetime and superfluid Helium, and proposals that suggest (...) spacetime is an emergent phenomenon arising from the edge states of a 4-dim Quantum Hall liquid. KeyworCh: spacetime, effective field theory, condensed matter, quantum gravity.. (shrink)

An introduction to the area of condensed matter in a nutshell. This textbook covers the standard topics, including crystal structures, energy bands, phonons, optical properties, ferroelectricity, superconductivity, and magnetism.

Corollaire à "l'homme mesure de toute chose" se place "l'homme démesure de toute chose". La démesure n'est pas dommageable en soi, ne pas prendre la mesure de cette démesure ni engager une culture préparant à digérer la démesure est par contre désastreux. Toute médiation est aussi facteur de démesure. Première des médiations humaines, le langage verbal entre dans un vertige de la démesure, à la mesure des médiations technologiques et de leur puissance inouïe. Cet essai sur la condensation se place (...) dans l'effort pour penser les fondements de la médiation symbolique et ce à partir d'une économie sensible de la représentation qui prend pour appui le langage plastique. Kim Leroy est docteur en Philosophie et lettres de l'Université libre de Bruxelles (2006). il enseigne la philosophie de l'art et la sémiologie des médias à l'académie royale des Beaux-arts de Bruxelles et à Arts2 à Mons. coopérateur à la coopérative Quatre Quarts à court-saint-Etienne, il est aussi observateur au conseil d'administration du Mundaneum à Mons et Membre de SEA (sustainable economy association). (shrink)

The complexity of aII 4 set of natural numbers is encoded into a linear order to show that the finite condensation of a recursive linear order can beII 2–II 1. A priority argument establishes the same result, and is extended to a complete classification of finite condensations iterated finitely many times.

This paper considers the issue of Bose–Einstein condensation in a weakly interacting Bose gas with a fixed total number of particles. We use an old current algebra formulation of non-relativistic many body systems due to Dashen and Sharp to show that, at sufficiently low temperatures, a gas of weakly interacting Bosons displays Off-diagonal Long Range Order in the sense introduced by Penrose and Onsager. Even though this formulation is somewhat cumbersome it may demystify many of the standard results in the (...) field for those uncomfortable with the conventional broken symmetry based approaches. All the physics presented here is well understood but as far as we know this perspective, although dating from the 60's and 70's, has not appeared in the literature. We have attempted to make the presentation as self-contained as possible in the hope that it will be accessible to the many students interested in the field. (shrink)

Many abiotic and other signals are transduced in eukaryotic cells by changes in the level of free calcium via pumps, channels and stores. We suggest here that ion condensation should also be taken into account. Calcium, like other counterions, is condensed onto linear polymers at a critical value of the charge density. Such condensation resembles a phase transition and has a topological basis in that it is promoted by linear as opposed to spherical assemblies of charges. Condensed counterions are delocalised (...) and can diffuse in the so‐called near region along the polymers. It is generally admitted that cytoskeletal filaments, proteins colocalised with these filaments, protein filaments distinct from cytoskeletal filaments, and filamentous assemblies of other macromolecules, constitute an intracellular macromolecular network. Here we draw attention to the fact that this network has physicochemical characteristics that enable counterion condensation. We then propose a model in which the feedback relationships between the condensation/decondensation of calcium and the activation of calcium‐dependent kinases and phosphatases control the charge density of the filaments of the intracellular macromolecular network. We show how condensation might help mediate free levels of calcium both locally and globally. In this model, calcium condensation/decondensation on the macromolecular network creates coherent patterns of protein phosphorylation that integrate signals. This leads us to hypothesize that the process of ion condensation operates in signal transduction, that it can have an integrative role and that the macromolecular network serves as an integrative receptor. BioEssays 26:549–557, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Inner speech has been shown to vary in form along several dimensions. Along condensation, condensed inner speech forms have been described, that are supposed to be deprived of acoustic, phonological and even syntactic qualities. Expanded forms, on the other extreme, display articulatory and auditory properties. Along dialogality, inner speech can be monologal, when we engage in internal soliloquy, or dialogal, when we recall past conversations or imagine future dialogues involving our own voice as well as that of others addressing us. (...) Along intentionality, it can be intentional (when we deliberately rehearse material in short-term memory) or it can arise unintentionally (during mind wandering). We introduce the ConDialInt model, a neurocognitive predictive control model of inner speech that accounts for its varieties along these three dimensions. ConDialInt spells out the condensation dimension by including inhibitory control at the conceptualization, formulation or articulatory planning stage. It accounts for dialogality, by assuming internal model adaptations and by speculating on neural processes underlying perspective switching. It explains the differences between intentional and spontaneous varieties in terms of monitoring. We present an fMRI study in which we probed varieties of inner speech along dialogality and intentionality, to examine the validity of the neuroanatomical correlates posited in ConDialInt. Condensation was also informally tackled. Our data support the hypothesis that expanded inner speech recruits speech production processes down to articulatory planning, resulting in a predicted signal, the inner voice, with auditory qualities. Along dialogality, covertly using an avatar’s voice resulted in the activation of right hemisphere homologues of the regions involved in internal own-voice soliloquy and in cerebellar deactivation, consistent with internal model adaptation. Switching from first-person to third-person perspective resulted in activations in precuneus and parietal lobules. Along intentionality, compared with intentional inner speech, mind wandering with inner speech episodes was associated with greater bilateral inferior frontal activation and decreased activation in left temporal regions. This is consistent with the reported subjective evanescence and presumably reflects condensation processes. Our results provide neuroanatomical evidence compatible with predictive control and in favor of the assumptions made in the ConDialInt model. (shrink)

ABSTRACT In this article I read Freud’s theory of dream condensation alongside Blanchot and Derrida’s analysis of the literary fragment. Both these thinkers describe how an imperturbable secret provides an excess that calls out for a response. I thus analyze the structure of dream interpretation as one where the latent dream thoughts respond to a call imbedded in the condensed dream-content. Through a deconstructive reading of Freud and a quote by Nietzsche, I argue that the structure of this call is (...) the condensation of the secret, which is both a mark and occurrence of forgetting. (shrink)

This paper gives a simple, elegant statement of the condensed detachment rule that is independent of most general unifiers and proves that this is equivalent to the longer, more usual, formulation.

The Hartree–Fock–Popov theory of interacting Bose particles is generalized to the Cooper-pair system with a screened Coulomb repulsive interaction in high-temperature superconductors. At zero temperature, it is found that the condensate density \\) of Cooper pairs is of the order \\simeq 10^{18}\) cm\, consistently with the fact that a small fraction of the total p holes participate in pairing. We find that the phonon velocity c at zero temperature is of the order \\simeq 10\) km s\. The computation shows that (...) the transition temperature \ is a dome-shaped function of the p hole concentration \, which is consistent with experiments. At finite temperature, we find that the condensate fraction \/n\) decreases continuously from \/n\) to zero as the temperature increases from zero to the transition temperature \. For higher temperatures, we find that the repulsive interaction between Cooper pairs drives more Cooper pairs into the condensate. The computation reveals that the phonon velocity c decreases continuously from c to zero as the temperature increases from zero to the transition temperature \. The Cooper-pair system undergoes a first-order phase transition from the normal state to the BEC state. (shrink)

We present the bundle (Aff(3)⊗ℂ⊗Λ)(ℝ3), with a geometric Dirac equation on it, as a three-dimensional geometric interpretation of the SM fermions. Each (ℂ⊗Λ)(ℝ3) describes an electroweak doublet. The Dirac equation has a doubler-free staggered spatial discretization on the lattice space (Aff(3)⊗ℂ)(ℤ3). This space allows a simple physical interpretation as a phase space of a lattice of cells.We find the SM SU(3) c ×SU(2) L ×U(1) Y action on (Aff(3)⊗ℂ⊗Λ)(ℝ3) to be a maximal anomaly-free gauge action preserving E(3) symmetry and symplectic (...) structure, which can be constructed using two simple types of gauge-like lattice fields: Wilson gauge fields and correction terms for lattice deformations.The lattice fermion fields we propose to quantize as low energy states of a canonical quantum theory with ℤ2-degenerated vacuum state. We construct anticommuting fermion operators for the resulting ℤ2-valued (spin) field theory.A metric theory of gravity compatible with this model is presented too. (shrink)