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At least 19 recordsLinked to original sources
PubMed1978

Chromosome condensation and radiation-induced G2 arrest studied by the induction of premature chromosome condensation following cell fusion.

When mitotic and interphase cells are fused together, the chromosomes of the interphase cell sometimes condense prematurely. The phenomenon of premature chromosome condensation (PCC) was utilized in investigating the problem of whether the chromosomes of cells suffering a radiation-induced G2 delay are capable of condensation. Colcemide-arrested mitotic cells were fused with synchronized G2 cells, and with irradiated cells suffering a G2 delay. The frequency of PCC in mitotic X G2 binucleate cells was determined. This was compared to the PCC frequency in an unirradiated synchronized population rich in G2 cells after fusion with mitotic cells. Flash-labelling with 3HTdR and autoradiography allowed us to eliminate S-phase cells. The frequency of G2 PCCs was not significantly different for the irradiated G2-delayed or unirradiated cells. From these results we conclude that the chromosomes of cells suffering a G2 arrest are capable of condensation, although the involvement of the condensation process in radiation-induced G2 delay cannot be ruled out.

Cell Cycle↗
PubMed1976

[Experimental studies on the rumorigenic activity of cigarette smoke condensate on mouse skin. VI. Fractionation of cigarette smoke condensate (author's transl)].

This experiment has been performed to clarify the question to which extent fractions containing polycyclic aromatic hydrocarbons (PAH) or other carcinogenic compounds are responsible for the biological activity of cigarette smoke condensate. With chromatographic procedures using organic gels it was possible to separate quantitatively polar compounds from the PAH-fraction and to obtain fraction IX representing 0.4% of the whole condensate. In this fraction the PAH were enriched 250fold. Significant losses of tumorigenic effects by this fractionation method could not be observed. This PAH-containing fraction showed 50% of activity compared with the overall activity of whole smoke condensate of a reference cigarette. A so-called PAH-free fraction showed with 7% of the overall activity of the whole smoke condensate a weak carcinogenic effect. The importance of PAH for the tumorigenic effect of cigarette smoke is emphasized by these results.

Animals↗
PubMed1976

[Experimental studies on tumorigenic activity of cigarette smoke condensate on mouse skin. V. Comparative studies of condensates from different modified cigarettes (author's transl)].

The tumorigenic effect of smoke condensates from reference cigarettes and different modified cigarettes has been investigated on the mouse skin. The following results have been obtained: 1. Reconstituted tobacco sheets made from the blend of the reference cigarette T as well as different other tobacco mixtures showed a reduced tumorigenic effect. 50% or 20% of reconstituted tobacco sheets as additive to the tobacco T showed reduced tumorigenic effect too. 2. A dark tobacco mixture (cigar type) as well as the Virginia tobacco of the mixture T showed no significant differences in biological activity compared to the reference tobacco. Condensate of the Burley tobacco of the blend T showed a reduced tumorigenic effect. 3. A small amount of nitrate as additive (1.8% total nitrate) only showed a limited reduction of the tumorigenic effect. 4. Condensate of a cigarette with commercially used filters, 20% reconstituted tobacco sheets and a total nitrate content of 1.8% showed a distinctly reduced tumorigenic effect. 5. Statistical evaluations of this experiment indicated that each of the applied dose should not be too high. Application of high doses did not lead to a further increase of tumor incidence. Cytotoxicity and viscosity of higher concentrated solutions may be responsible for this fact.

Animals↗
PubMed1977

[Experimental investigations on the tumorigenic activity of cigarette smoke condensate on mouse skin. VII. Comparative studies of condensates from different modified cigarettes (author's transl)].

Condensate from different modified cigarettes were compared with condensate from a standard cigarette with regard to its tumorigenic activity on mouse skin. Significant lower effects were observed in test series with cigarettes from expanded tobacco. Different results were obtained in experiments with cigarettes from the new smoking materials. In one case the effect was higher, in two another cases the effect was lower in comparison to the effect of condensate from reference cigarettes. A certain influence may be referred to the diameter of the cigarette, i.e. a thinner cigarette shows a lower biological effect. The lowest tumoringenic effect was observed in tests with cigarettes with a high content of Burley-stems.

Animals↗
PubMed2026

Integrative chemical genetics platform identifies condensate modulators linked to neurological disorders.

Dysregulation of biomolecular condensates is implicated across multiple neurological disorders. However, approaches to systematically identify their modulators remain limited. Here, we expand the utility of MLF2 as a versatile condensate biomarker and develop CondenScreen, an integrated high-content screening and bioinformatics pipeline enabling identification of condensate modulators across chemical and genetic space. Screening 1760 bioactive compounds in a cellular DYT1 dystonia model, we validate the platform for condensate-targeted drug discovery, identifying drugs that prevent the accumulation of the MLF2 reporter into nuclear envelope condensates. In parallel, a genome-wide CRISPR/Cas9 screen correlates nuclear condensate abundance with genes implicated in microcephaly and over eight additional neurodevelopmental disorders. Machine learning and confocal imaging resolve distinct condensate phenotypes, with RNF26 deletion provoking nuclear envelope condensates that phenocopy hallmarks of torsin deficiency. Our study provides a scalable platform for identifying modulators of condensates and establishes a correlative connection between nuclear condensate accumulation and genes implicated in neurodevelopmental disorders.

Humans↗
PubMed1978

Ion-molecule condensation reactions: a mechanism for organic synthesis in ionized reducing atmospheres.

The CH3+ ion, formed in ionized methane, undergoes consecutive eliminative condensation reactions with methane to form the carbonium ions C2H5+, i-C3H7+ and t-C4H9+. At T smaller than 500 degrees K, NCH4 greater than 10(16) cm-3 these ions react with NH3 in competitive condensation -- H+ transfer reactions, e.g. C2H5 + NH3 M leads to C2H5NH3+ leads to NH4+ + C2H4 At particle densities of NCH4 smaller than 10(16) cm-3 proton transfer is the only significant reaction channel. At NCH4 greater than 10(17) cm-3 condensation constitutes 5--20% of the overall reactions. The product of the condensation reaction further associates with CO2 to form C2H5NH3+ . CO2; the atomic composition of this cluster ion is identical with the protonated amino acid alanine. The carbonium ions i-C3H7+ and t-C4H9+ condense also with HCN to yield protonated isocyanides. HCNH% also appears to condense with HCN at T greater than 570 degrees K, and form cluster ions with HCN at lower temperatures. The rate constants of the condensation reactions vary with temperature and pressure in a complex manner. Under conditions similar to those on Titan at an altitude of 100 km (T = 100--150 degrees K, NCH4 approximately 10(18) cm-3), with a methane atmosphere containing 1% H2 and traces of NH3 and H2O, ion-molecule condensation reactions followed by H+ transfer are expected to lead to the atmospheric synthesis of C2H6, C3H8, CH3OH, C2H5OH and the terminal ions NH4+, CH3NH3+ and C2H5NH3+. At higher temperatures (250 degrees K smaller than T smaller than 400 degrees K), the synthesis of i-C4H10, i-C3H7OH and t-C4H9OH and of the ions i-C3H7NH3+ and t-C4H9NH3+ is also expected. Electron recombination of the terminal ions may yield amines, imines and nitriles. Cycles of protonation and dissociative recombination of the alkanes and alcohols produced in condensation reactions will also produce unsaturated hydrocarbons, ketones and aldehydes in the ionized atmosphere.

Amines↗
PubMed1979

Reduction in mutagenicity of cigarette smoke condensate by added sugars.

The effects of adding sugars to high- and low-tar cigarettes on the mutagenicity of their smoke condensates were studied using Salmonella typhimurium TA100 and TA98 with and without metabolic activation. The sugars tested were glucose, fructose, galactose, sorbitol, sucrose and lactose. The lowest mutagenicities observed with these sugars per mg of smoke condensate assayed on TA98 with metabolic activation were 37% (high-tar cigarettes) and 22% (low-tar cigaretts) of that of smoke condensate from untreated cigarettes. Addition of sugars increased the total amounts of smoke condensates, but the mutagenicities of the total condensates were also decreased by all the sugars, the lowest values being 35% (high-tar cigarettes) and 36% (low-tar cigarettes) of that of smoke condensates from cigarettes without added sugar. On assay with TA100 with metabolic activation, decreases in both specific and total mutangenicities of condensates of high-tar cigarettes were observed with all the sugars tested except galactose and sucrose. Treatment with glucose, fructose or sorbitol decreased the specific mutagenicity of condensates of low-tar cigarettes and glucose and fructose reduced also their total mutagenicity. The effects of added sugars were more marked when assayed on TA98 than on TA100 and of the sugars tested fructose and sorbitol had the greatest effects. Addition of sugars had no effect of the mutagenicity of cigarette-smoke condensate without metabolic activation.

Carbohydrates↗
PubMed2025

An RNA Condensate Model for the Origin of Life.

The RNA World hypothesis predicts that self-replicating RNAs evolved before DNA genomes and coded proteins. Despite widespread support for the RNA World, self-replicating RNAs have yet to be identified in a natural context, leaving a key 'missing link' for this explanation of the origin of life. Inspired by recent work showing that condensates of charged polymers are capable of catalyzing chemical reactions, we consider a catalytic RNA condensate as a candidate for the self-replicating RNA. Specifically, we propose that short, low-complexity RNA polymers formed catalytic condensates capable of templated RNA polymerization. Because the condensate properties depend on the RNA sequences, RNAs that formed condensates with improved polymerization and demixing capacity would be amplified, leading to a 'condensate chain reaction' and evolution by natural selection. Many of the needed properties of this self-replicating RNA condensate have been realized experimentally in recent studies and our predictions could be tested with current experimental and theoretical tools. Our theory addresses central problems in the origins of life: (i) the origin of compartmentalization, (ii) the error threshold for the accuracy of templated replication, (iii) the free energy cost of maintaining an information-rich population of replicating RNA polymers. Furthermore, we note that the extant nucleolus appears to satisfy many of the requirements of an evolutionary relic for the model we propose. More generally, we suggest that future work on the origin of life would benefit from condensate-centric biophysical models of RNA evolution.

Origin of Life↗
PubMed2026

Bridging-driven condensation by eukaryotic SMC complexes is a conserved feature of genome organization.

The Structural Maintenance of Chromosome (SMC) protein family plays a central role in higher-order genome organization through ATP-dependent DNA loop extrusion by cohesin and condensin and other processes. Whether these activities fully account for the complexity of chromosome architecture remains unknown. Here, we uncover a conserved ATP-independent mechanism of chromatin condensation by SMC complexes, occurring via biomolecular condensation. Using single-molecule fluorescence imaging, we show that a variety of SMCs form dynamic DNA-bound condensates that exhibit key features of biomolecular condensates, including droplet coalescence, fluorescence recovery after photobleaching, and rapid exchange with free SMC complexes. Atomic force microscopy analysis of human cohesin-DNA assemblies reveals DNA-length-dependent clustering, providing evidence for bridging-driven condensation. Analyses of in vivo super-resolution imaging and high-throughput chromosome conformation capture (Hi-C) data indicate that these condensates form chromatin-associated clusters with multi-loop structures. Together, our results establish that SMC complexes employ ATP-independent phase condensation as well as ATP-dependent activities to shape genome architecture. This work reveals a broadly conserved principle of chromosomal organization across eukaryotes.

Chromosomal Proteins, Non-Histone↗
PubMed2026

Emergent 3D genome reorganization and graded gene control from the stepwise assembly of transcriptional condensates.

Transcriptional condensates are clusters of transcription factors, coactivators, and RNA Pol II associated with gene activation, yet how they assemble and function within the cell remains unclear. Here, we show that transcriptional condensates form in a stepwise manner to enable both graded and three-dimensional (3D) gene control in the yeast heat shock response (HSR). First, the transcription factor Hsf1 (heat shock factor 1) clusters upon partial dissociation from the chaperone Hsp70. Next, the coactivator Mediator partitions following further Hsp70 dissociation and Hsf1 phosphorylation. Finally, Pol II condenses, driving emergent coalescence of HSR genes. Separation-of-function Hsf1 mutants revealed graded (non-switch-like) control of transcription and a decoupling of condensate formation and gene activation. Fully assembled HSR condensates promoted adaptive 3D genome reconfiguration, suggesting a role beyond transcription. In the HSR, differential condensation of the transcriptional machinery quantitatively tunes gene expression and qualitatively remodels the 3D genome.

3D genome↗
PubMed2026

From pan-life phase insights to PhaseHub: Analyzing protein condensate complexity.

Intracellular biomolecular condensation forms multicomponent signaling hubs that regulate development, stress responses, and environmental adaptation. While the molecular grammar encoded within scaffold proteins defines the basal associative features driving condensation, heterotypic condensates are intrinsically dynamic, multicomponent, and far-from-equilibrium systems. Consequently, how condensates organize component composition, stoichiometry, and functional specificity in space and time under physiological conditions remains poorly understood. Addressing this challenge requires integrative frameworks that combine predictive biophysical features with experimental information on protein abundance, interaction networks, subcellular localization, and evolutionary conservation. In this study, we first analyzed phase separation (PS) proteins across the tree of life in 1106 species, revealing a stark contrast in computationally predicted PS propensity between eukaryotes and prokaryotes, with genome size as a key determinant. Through a broad analysis of amino acid homorepeat-containing proteins (HRPs) across all species, we uncovered how PS evolves via a balance between functional condensation and avoidance of harmful, aggregation-prone sequences. We further identified potential signaling hubs and components across kingdoms by integrating PS-positive proteins with experimentally derived abundance and interactome data from four model eukaryotic species. Using Arabidopsis as a model, we dissected the relationships among PS propensity, condensation hub prediction, HRPs, subcellular localization, and structural conservation. Finally, we developed PhaseHub, a user-friendly interface for exploring scaffold-client dynamics, PS components, sequence signatures within each PS protein, and hubs. Collectively, our work provides an evolutionary framework for understanding multicomponent PS hubs by integrating molecular grammar with physiological context, thereby facilitating hypothesis generation and rational design.

Phase Separation↗
PubMed2025

Live-Cell Monitoring and Omics Analysis of Liquid-Solid Transitions of Biomolecular Condensates.

Biomolecular condensates, or so-called membraneless organelles, transition from liquid into more solid-like states over time, contributing to the development of pathological conditions. The present study proposes a simple method using photoactive yellow protein (PYP) and its specific fluorescent covalent ligands to distinguish between the liquid and solid states of protein condensates in live cells. The method, compatible with fluorescence-activated cell sorting (FACS), correlates the stiffness of specific protein condensates with their accessibility to PYP ligands, enabling quantitative multicolor monitoring of condensate solidification. We applied this technique to 12 phase-separating proteins and their mutants, finding that TDP-43, particularly its A315T mutant linked to familial amyotrophic lateral sclerosis, most readily forms solid aggregates. Furthermore, this FACS-compatible strategy enabled the isolation of distinct cell populations based on condensate states, allowing for subsequent proteomic and transcriptomic analyses. Our findings demonstrate that condensate solidification is accompanied by the upregulated expression of extracellular matrix proteins, suggesting a previously unrecognized link between solid aggregate formation and extracellular matrix hardening.

Humans↗
PubMed2026

High-throughput identification of endogenous biomolecular condensates and phase-separating proteins.

Biomolecular condensates formed through liquid-liquid phase separation regulate cellular processes, and their dysregulation causes disease. Current methods for identifying endogenous phase-separating proteins have low throughput and cannot capture dynamic responses to stimuli. Here we present a protocol combining osmotic compression or transforming growth factor-β (TGF-β) treatment to induce condensation with sucrose density gradient centrifugation and quantitative mass spectrometry to enable systematic, high-throughput identification of endogenous condensates and phase-separating proteins. The method exploits the density changes that occur when phase-separating proteins undergo oligomerization during condensate formation. In H1975 cells, we identified over 1,500 phase-separating proteins under osmotic compression or TGF-β treatment; 538 of these candidates were not present in PhaSepDB, a database that compiles in vivo, in vitro and omics-derived proteins. The approach detects constitutive condensates and proteins that dynamically phase-separate in response to osmotic stress or TGF-β signaling. This protocol provides proteome-wide analysis of fractions of proteins having different densities and enables temporal resolution of phase-separation events. The procedure takes ~9 d and requires expertise in cell culture, biochemistry and mass spectrometry. This method enables systematic study of biomolecular condensates and disease-associated phase-separation mechanisms.

Phase Separation↗
PubMed1976

The possible role of solid surface area in condensation reactions during chemical evolution: reevaluation.

Published data on adsorption and condensation of amino acids, purine and pyrimidine bases, sugars, nucleosides, and nucleotides are analyzed in connection with Bernal's hypothesis that clays and other minerals may have provided the most likely surface for adsorption and condensation of these molecules in prebiotic times. Using surface concentration and reaction rate as the main criteria for the feasibility of condensation reactions, four types of prebiotic environments were analyzed: (1) an ocean-sediment system, (2) a dehydrated lagoon bed produced by evaporation, (3) the surface of a frozen sediment, and (4) a fluctuating system where hydration (rainstorms, tidal variations, flooding) and dehysration (evaporation) take place in a cyclic manner. With the possible exception of nucleotides, low adsorption of organomonomers on sediment surfaces of a prebiotic ocean (pH 8) is expected, and significant condensation is considered unlikely. In dehydrated and frozen systems, high surface concentrations are probable and condensation is more likely. In fluctuating environments, condensation rates will be enhanced and the size distribution of the oligomers formed during dehydration may be influenced by a "redistribution mechanism" in which adsorbed oligomers and monomers are desorbed and redistributed on the solid surface during the next hydration-dehydration cycle.

Adsorption↗
PubMed1977

Relation between chemical constituents of tobacco and mutagenic activity of cigarette smoke condensate.

Mutagenic activities of cigarette smoke condensate were assayed in the presence of S-9 Mix using Salmonella typhimurium TA 98. The results were examined in relation to chemical data of tobacco leaves. Among the nitrogenous constituents examined, the contents of total nitrogen and protein nitrogen and the soluble nitrogenous fraction were positively and significantly related to an increase in mutagenic activity of the smoke condensate, whereas nicotine and nitrate were not important in contributing to mutagenic potency of such condensates. The age of tobacco leaves influenced the mutagenic potency of the condensate, which was lowest in leaves from the lower stalk position and increased with ascending leaf position on the stalk. Smoke condensate from tobacco with higher sugar content resulted in lower mutagenic activity. The present results, together with the previous study on the mutagenicity of the amino acid pyrolyzates, suggest that potent mutagens in cigarette smoke condensate are nitrogen-containing compounds, which may be formed from proteins and amino acids during the burning of a cigarette.

Amino Acids↗
PubMed1977

Studies on the local and systemic carcinogenicity of topically applied smoke condensate from a substitute smoking material.

The topical carcinogenicity to mouse skin of smoke condensates obtained from a tobacco substitute (NSM), alone or in combination with tobacco, has been compared with condensate from tobacco and with acetone, the solvent used. Sixteen different types of cigarette were used to make the condensates, and the age-standardized results have been analysed according to the Weibull distribution model. The results show that NSM condensate has less than 25% of the potency of tobacco condensate (37% at 95% upper confidence limit), and that condensates from blends of NSM and tobacco are similarly reduced in activity. General pathology analysis failed to reveal abnormalities due to NSM.

Animals↗
PubMed2026

NAP1 switches from an activator to a limiter of interferon induction by trapping TBK1 in condensates.

TBK1 kinase is a central regulator of type I IFN production. Upon activation of the IFN-β induction pathway, TBK1-adaptor proteins (NAP1, SINTBAD, TANK) form liquid condensates. We show that NAP1 condensates concentrate TBK1. Using NAP1KO cell lines, we demonstrate that NAP1 exerts a dual effect on TBK1 activity. Initially, NAP1 binds TBK1 and increases its activity, promoting IFN pathway activation. Subsequently, TBK1-mediated phosphorylation of NAP1 induces the formation of condensates. These NAP1 condensates concentrate both TBK1 and the phosphatase PP2A, which dephosphorylates and consequently deactivates TBK1, thus limiting IFN induction. Additionally, in patients with lupus or interferonopathies, we identify NAP1 variants unable to form condensates upon danger signal exposure, which sustain TBK1 activation without limiting its activity. This study reveals a mode of regulating a signaling pathway through condensate formation and provides a potential molecular explanation for immune dysregulation associated with NAP1 variants in certain patients with interferonopathies.

Protein Serine-Threonine Kinases↗