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We study phase-separation kinetics of symmetric diblock copolymer (BCP) melt in $3d$ 3 d subjected to sequential light on/off cycles. The incompatible blocks of each BCP chain are connected by a photosensitive bond, which undergoes breakage during photo-illumination (on-cycle) and recombination during the off-cycle. We set a shorter fixed time limit for each on-cycles and focus on analysing how the much longer duration of the light off-cycles affects the segregation kinetics. We explore two scenarios for each off-cycle time variation: one with equal and another with increasing durations. For both cases, we determine the rate constants for bond formation and degradation reactions and assess their influence on the dynamical scaling functions and the growth scale of evolving morphologies. The average domain size typically exhibits diffusive growth ($R\lpar t\rpar \sim t^{1/3}$ R (t) ∼ t 1 / 3 ) for a couple of cycles in the beginning. However, the domain growth nearly freezes during the rest of the cycles, resulting in bicontinuous and nearly frozen isotropic morphologies. [ABSTRACT FROM AUTHOR]

nArgBP2, a protein whose disruption is implicated in intellectual disability, concentrates in excitatory spine-synapses. By forming a triad with GKAP and SHANK, it regulates spine structural rearrangement. We here find that GKAP and SHANK3 concentrate close to the synaptic contact, whereas nArgBP2 concentrates more centrally in the spine. The three proteins collaboratively form biomolecular condensates in living fibroblasts, exhibiting distinctive layered localizations. nArgBP2 concentrates in the inner phase, SHANK3 in the outer phase, and GKAP partially in both. Upon co-expression of GKAP and nArgBP2, they evenly distribute within condensates, with a notable peripheral localization of SHANK3 persisting when co-expressed with either GKAP or nArgBP2. Co-expression of SHANK3 and GKAP with CaMKIIα results in phasein-phase condensates, with CaMKIIα at the central locus and SHANK3 and GKAP exhibiting peripheral localization. Additional co-expression of nArgBP2 maintains the layered organizational structure within condensates. Subsequent CaMKIIα activation disperses a majority of the condensates, with an even distribution of all proteins within the extant deformed condensates. Our findings suggest that protein segregation via phase separation may contribute to establishing layered organization in dendritic spines. [ABSTRACT FROM AUTHOR]

Blending different types of polymers with traces of a telechelic macromolecule that is end‐functionalized with excimer‐forming chromophores affords materials that display a highly sensitive, reversible, and strain‐dependent mechanochromic response. Confocal microscopy imaging reveals that the additive forms discrete, phase‐separated inclusions in host polymers such as poly(ε‐caprolactone), poly‐isoprene, poly(styrene‐b‐butadiene‐b‐styrene), and different thermoplastic polyurethanes. A comprehensive analysis shows that the mechanochromism of the blends originates from the distortion of the inclusions, which, independent of the additive content and chemical composition of the matrix, deform homogeneously and reversibly in response to the applied macroscopic strain. These findings support the conclusion that such excimer‐forming, telechelic macromolecules can be used as universal additives that allow the straightforward fabrication of a wide range of mechanochromic materials. [ABSTRACT FROM AUTHOR]

Membraneless organelles (MLOs) are vital and dynamic reaction centers in cells that compartmentalize the cytoplasm in the absence of a membrane. Multivalent interactions between protein low-complexity domains contribute to MLO organization. Previously, we used computational methods to identify structural motifs termed low-complexity amyloid-like reversible kinked segments (LARKS) that promote phase transition to form hydrogels and that are common in human proteins that participate in MLOs. Here, we searched for LARKS in the proteomes of six model organisms: Homo sapiens, Drosophila melanogaster, Plasmodium falciparum, Saccharomyces cerevisiae, Mycobacterium tuberculosis, and Escherichia coli to gain an understanding of the distribution of LARKS in the proteomes of various species. We found that LARKS are abundant in M. tuberculosis, D. melanogaster, and H. sapiens but not in S. cerevisiae or P. falciparum. LARKS have high glycine content, which enables kinks to form as exemplified by the known LARKS-rich amyloidogenic structures of TDP43, FUS, and hnRNPA2, three proteins that are known to participate in MLOs. These results support the idea of LARKS as an evolved structural motif. Based on these results, we also established the LARKSdb Web server, which permits users to search for LARKS in their protein sequences of interest.

Poly(β-hydroxybutyrate) (PHB) is a well-known biodegradable bio-based polymer but can be brittle. Polymer blending of PHB with polyethylene (PE) or polypropylene (PP) has been proposed to improve the mechanical properties. Compatibilizers have been considered to improve the performance of the polymer blend with PHB; however, the effect of compatibilizers on biodegradation is controversial. In the present study, the PHB polymer was blended with PP, a non-biodegradable synthetic polymer, and spun into fiber form. Furthermore, the effect of increased interaction between the polymers was investigated by increasing the miscibility with compatibilizer, maleic anhydride-grafted polypropylene (MAPP). The biodegradation of PHB in the blends was investigated in aquatic aerobic conditions with a closed respirometer with activated sludge as inoculum. Since PP is not a biodegradable polymer, the PHB-based biodegradation was calculated based on the ratio of oxygen consumption to the theoretical oxygen demand of PHB polymer in the blends. The fibers with a concentration of PHB below 75% showed a significant decrease in PHB biodegradation. This result confirms that non-biodegradable polymers in the blend can hinder the biodegradation of biodegradable polymers. Additionally, this blending is shown herein to have unintended consequences, creating micro and nano pollution of residual synthetic PP material. MAPP has an effect of increasing the miscibility between PP and PHB; however, this increased miscibility rendered the PHB biodegradation to be very low, less than 25%. This result suggests that even though increased miscibility can improve mechanical performance, it can decrease the biodegradation of biodegradable polymers in non-biodegradable/biodegradable polymer blends. [ABSTRACT FROM AUTHOR]

The organization of chromatin into different types of compact versus open states provides a means to fine tune gene regulation. Recent studies have suggested a role for phase-separation in chromatin compaction, raising new possibilities for regulating chromatin compartments. This perspective discusses some specific molecular mechanisms that could leverage such phase-separation processes to control the functions and organization of chromatin.

Understanding the mechanisms underlying the complex 3D architecture of mammalian genomes poses, at a more fundamental level, the problem of how two or multiple genomic sites can establish physical contacts in the nucleus of the cells. Beyond stochastic and fleeting encounters related to the polymeric nature of chromatin, experiments have revealed specific, privileged patterns of interactions that suggest the existence of basic organizing principles of folding. In this review, we focus on two major and recently proposed physical processes of chromatin organization: loop-extrusion and polymer phase-separation, both supported by increasing experimental evidence. We discuss their implementation into polymer physics models, which we test against available single-cell super-resolution imaging data, showing that both mechanisms can cooperate to shape chromatin structure at the single-molecule level. Next, by exploiting the comprehension of the underlying molecular mechanisms, we illustrate how such polymer models can be used as powerful tools to make predictions in silico that can complement experiments in understanding genome folding. To this aim, we focus on recent key applications, such as the prediction of chromatin structure rearrangements upon disease-associated mutations and the identification of the putative chromatin organizing factors that orchestrate the specificity of DNA regulatory contacts genome-wide. [ABSTRACT FROM AUTHOR]

Abstract Background Acute myeloid leukemia (AML) is characterized by accumulation of aberrantly differentiated hematopoietic myeloid progenitor cells. The karyotyping-silent NUP98-NSD1 fusion is a molecular hallmark of pediatric AML and is associated with the activating FLT3-ITD mutation in > 70% of the cases. NUP98-NSD1 fusion protein promotes myeloid progenitor self-renewal in mice via unknown molecular mechanism requiring both the NUP98 and the NSD1 moieties. Methods We used affinity purification coupled to label-free mass spectrometry (AP-MS) to examine the effect of NUP98-NSD1 structural domain deletions on nuclear interactome binding. We determined their functional relevance in NUP98-NSD1 immortalized primary murine hematopoietic stem and progenitor cells (HSPC) by inducible knockdown, pharmacological targeting, methylcellulose assay, RT-qPCR analysis and/or proximity ligation assays (PLA). Fluorescence recovery after photobleaching and b-isoxazole assay were performed to examine the phase transition capacity of NUP98-NSD1 in vitro and in vivo. Results We show that NUP98-NSD1 core interactome binding is largely dependent on the NUP98 phenylalanine-glycine (FG) repeat domains which mediate formation of liquid-like phase-separated NUP98-NSD1 nuclear condensates. We identified condensate constituents including imitation switch (ISWI) family member SMARCA5 and BPTF (bromodomain PHD finger transcription factor), both members of the nucleosome remodeling factor complex (NURF). We validated the interaction with SMARCA5 in NUP98-NSD1+ patient cells and demonstrated its functional role in NUP98-NSD1/FLT3-ITD immortalized primary murine hematopoietic cells by genetic and pharmacological targeting. Notably, SMARCA5 inhibition did not affect NUP98-NSD1 condensates suggesting that functional activity rather than condensate formation per se is crucial to maintain the transformed phenotype. Conclusions NUP98-NSD1 interacts and colocalizes on the genome with SMARCA5 which is an essential mediator of the NUP98-NSD1 transformation in hematopoietic cells. Formation of NUP98-NSD1 phase-separated nuclear condensates is not sufficient for the maintenance of transformed phenotype, which suggests that selective targeting of condensate constituents might represent a new therapeutic strategy for NUP98-NSD1 driven AML.

The polyvinylidene fluoride (PVDF) membranes were synthesized using immersion precipitation technique. The effect of four solvents, N, N-dimethyl formamide (DMF), N, N-dimethylacetamide (DMAC), N-methyl-2-pyrrolidone (NMP), and dimethyl sulfoxide (DMSO) on the water flux and beef serum albumin (BSA) rejection efficiency was reported. The structure and morphology of PVDF membranes were studied using Scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and water contact angle measurements. The cross-section of a membrane formed in a DMF as a solvent exhibit a spongy/fingerlike hybrid structure, while DMSO favors the formation of more porous structure. The increase in the solvent mass fraction facilitates liquid phase separation and solution casting, and changes the structure of PVDF membrane from denser, bicontinuous structure to a looser, stacked structure. Moreover, the results revealed that the properties of PVDF membranes sub-layer are controlled by the diffusion rate of the nonsolvent. The membrane with the best performance was prepared using 80% DMF (mass fraction) as a solvent, and it reached water flux of 66 L·m−2·h−1, and 91.53% BSA rejection efficiency. [ABSTRACT FROM AUTHOR]

Within cell nuclei, several biophysical processes occur in order to allow the correct activities of the genome such as transcription and gene regulation. To quantitatively investigate such processes, polymer physics models have been developed to unveil the molecular mechanisms underlying genome functions. Among these, phase-separation plays a key role since it controls gene activity and shapes chromatin spatial structure. In this paper, we review some recent experimental and theoretical progress in the field and show that polymer physics in synergy with numerical simulations can be helpful for several purposes, including the study of molecular condensates, gene-enhancer dynamics, and the three-dimensional reconstruction of real genomic regions. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms underlying the complex 3D architecture of mammalian genomes poses, at a more fundamental level, the problem of how two or multiple genomic sites can establish physical contacts in the nucleus of the cells. Beyond stochastic and fleeting encounters related to the polymeric nature of chromatin, experiments have revealed specific, privileged patterns of interactions that suggest the existence of basic organizing principles of folding. In this review, we focus on two major and recently proposed physical processes of chromatin organization: loop-extrusion and polymer phase-separation, both supported by increasing experimental evidence. We discuss their implementation into polymer physics models, which we test against available single-cell super-resolution imaging data, showing that both mechanisms can cooperate to shape chromatin structure at the single-molecule level. Next, by exploiting the comprehension of the underlying molecular mechanisms, we illustrate how such polymer models can be used as powerful tools to make predictions in silico that can complement experiments in understanding genome folding. To this aim, we focus on recent key applications, such as the prediction of chromatin structure rearrangements upon disease-associated mutations and the identification of the putative chromatin organizing factors that orchestrate the specificity of DNA regulatory contacts genome-wide.

Background: Acute myeloid leukemia (AML) is characterized by accumulation of aberrantly differentiated hematopoietic myeloid progenitor cells. The karyotyping-silent NUP98-NSD1 fusion is a molecular hallmark of pediatric AML and is associated with the activating FLT3-ITD mutation in > 70% of the cases. NUP98-NSD1 fusion protein promotes myeloid progenitor self-renewal in mice via unknown molecular mechanism requiring both the NUP98 and the NSD1 moieties. Methods: We used affinity purification coupled to label-free mass spectrometry (AP-MS) to examine the effect of NUP98-NSD1 structural domain deletions on nuclear interactome binding. We determined their functional relevance in NUP98-NSD1 immortalized primary murine hematopoietic stem and progenitor cells (HSPC) by inducible knockdown, pharmacological targeting, methylcellulose assay, RT-qPCR analysis and/or proximity ligation assays (PLA). Fluorescence recovery after photobleaching and b-isoxazole assay were performed to examine the phase transition capacity of NUP98-NSD1 in vitro and in vivo. Results: We show that NUP98-NSD1 core interactome binding is largely dependent on the NUP98 phenylalanine-glycine (FG) repeat domains which mediate formation of liquid-like phase-separated NUP98-NSD1 nuclear condensates. We identified condensate constituents including imitation switch (ISWI) family member SMARCA5 and BPTF (bromodomain PHD finger transcription factor), both members of the nucleosome remodeling factor complex (NURF). We validated the interaction with SMARCA5 in NUP98-NSD1+ patient cells and demonstrated its functional role in NUP98-NSD1/FLT3-ITD immortalized primary murine hematopoietic cells by genetic and pharmacological targeting. Notably, SMARCA5 inhibition did not affect NUP98-NSD1 condensates suggesting that functional activity rather than condensate formation per se is crucial to maintain the transformed phenotype. Conclusions: NUP98-NSD1 interacts and colocalizes on the genome with SMARCA5 which is an essential mediator of the NUP98-NSD1 transformation in hematopoietic cells. Formation of NUP98-NSD1 phase-separated nuclear condensates is not sufficient for the maintenance of transformed phenotype, which suggests that selective targeting of condensate constituents might represent a new therapeutic strategy for NUP98-NSD1 driven AML. [ABSTRACT FROM AUTHOR]

Liquid-liquid phase separation (LLPS) is a way to concentrate biochemical reactions while excluding noninteracting components. Disordered domains of proteins, as well as interaction with RNA, favor condensation but are not mandatory for modulating this process. Recent insights about phase-separation mechanisms pointed to new fascinating models that could explain how cells could cope with DNA damage responses, conferring both spatial and temporal fine regulation. APE1 is a multifunctional protein belonging to the Base Excision Repair (BER) pathway, bearing additional ‘non-canonical’ DNA-repair functions associated with processes like RNA metabolism. Recently, it has been highlighted that several DNA repair enzymes, such as 53BP1 and APE1, are endowed with RNA binding abilities. In this work, after reviewing the recent literature supporting a role of LLPS in DDR, we analyze, as a proof of principle, the interactome of APE1 using a bioinformatics approach to look for clues of LLPS in BER. Some of the APE1 interactors are associated with cellular processes in which LLPS has been either proved or proposed and are involved in different pathogenic events. This work might represent a paradigmatical pipeline for evaluating the relevance of LLPS in DDR.

Procyanidin extracted from fruits, such as apples, has been shown to improve lipid metabolization. Recently, studies have revealed that procyanidin interacts with lipid molecules in membranes to enhance lipid metabolism; however, direct evidence of the interaction between procyanidin and lipid membranes has not been demonstrated. In this study, the phase behaviors and changes in the membrane fluidity of cell-sized liposomes containing apple procyanidin, procyanidin B2 (PB2), were demonstrated for the first time. Phase separation in 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/cholesterol ternary membranes significantly decreased after the addition of PB2. The prospect of applying procyanidin content measurements, using the results of this study, to commercial apple juice was also assessed. Specifically, the PB2 concentrations were 50%, 33%, and 0% for pure apple juice, 2-fold diluted apple juice, and pure water, respectively. The results of the actual juice were correlated with PB2 concentrations and phase-separated liposomes ratios, as well as with the results of experiments involving pure chemicals. In conclusion, the mechanism through which procyanidin improves lipid metabolism through the regulation of membrane fluidity was established.

MicroRNA (miRNA)-mediated translational suppression of mRNAs is involved in the regulation of multiple cellular processes. A recent study showed that Nup358, a protein mutated in a neurological disorder called acute necrotizing encephalopathy 1 (ANE1), helps in the coupling of miRNA-induced silencing complex (miRISC) - consisting of miRNA, AGO and GW182/TNRC6 proteins - with the target mRNA. Here we provide a detailed characterization of the interaction between Nup358 and GW182. We identified that the N-terminal region of Nup358 directly interacts with the C-terminal silencing domain of GW182. Interestingly, ANE1-associated Nup358 mutants display reduced interaction with GW182. Consistent with this, one of the prevalent ANE1 mutations, 585th threonine (T) residue changed to methionine (M) [T585M] compromised Nup358's ability to function in the miRNA pathway. Collectively, these results suggest that the ANE1-associated mutations in Nup358 might affect the miRNA pathway and contribute to the development of ANE1. • N-terminal region of Nup358 interacts with the C-terminal silencing domain of GW182. • ANE1-associated mutations compromise the interaction of Nup358 with GW182. • Most prevalent ANE1 mutation, T585M, interferes with Nup358's function in miRNA pathway. • T585M mutation does not affect oligomerization property of Nup358-N or interaction with PKCζ, Dvl1 or AGO2. [ABSTRACT FROM AUTHOR]

In this article, we present the behavior of two‐mode phase field crystal (2MPFC) method under a concentration dependent deformation. A mixed finite element formulation is proposed for the 2MPFC method that solves a 10th‐order parabolic equation. Lithium concentration diffusion in the electrode particle is captured by the Cahn–Hilliard (CH) equation and the host electrode material, LixMn2O4 (LMO), which has a face‐centered cubic (fcc) lattice structure, is modeled using 2MPFC. The coupling between 2MPFC and CH models brings about the concentration dependent deformation in the polycrystalline LMO electrode particle. The atomistic dynamics is assumed to operate on a faster time‐scale compared to the diffusion of lithium, thereby both the 2MPFC and CH models evolve on two different time‐scales. The coupled 2MPFC–CH system models the diffusion induced grain boundary migration in LMO capturing the charging and discharging state of the battery. [ABSTRACT FROM AUTHOR]

Within cell nuclei, several biophysical processes occur in order to allow the correct activities of the genome such as transcription and gene regulation. To quantitatively investigate such processes, polymer physics models have been developed to unveil the molecular mechanisms underlying genome functions. Among these, phase-separation plays a key role since it controls gene activity and shapes chromatin spatial structure. In this paper, we review some recent experimental and theoretical progress in the field and show that polymer physics in synergy with numerical simulations can be helpful for several purposes, including the study of molecular condensates, gene-enhancer dynamics, and the three-dimensional reconstruction of real genomic regions.

Higher-order spatial organization of the genome into chromatin compartments (permissive and repressive), self-associating domains (TADs), and regulatory loops provides structural integrity and offers diverse gene regulatory controls. In particular, chromatin regulatory loops, which bring enhancer and associated transcription factors in close spatial proximity to target gene promoters, play essential roles in regulating gene expression. The establishment and maintenance of such chromatin loops are predominantly mediated involving CTCF and the cohesin machinery. In recent years, significant progress has been made in revealing how loops are assembled and how they modulate patterns of gene expression. Here we will discuss the mechanistic principles that underpin the establishment of three-dimensional (3D) chromatin structure and how changes in chromatin structure relate to alterations in gene programs that establish immune cell fate.

Transportin-1 (Trn1), also known as karyopherin-β2 (Kapβ2), is probably the best-characterized nuclear import receptor of the karyopherin-β family after Importin-β, but certain aspects of its functions in cells are still puzzling or are just recently emerging. Since the initial identification of Trn1 as the nuclear import receptor of hnRNP A1 ∼25 years ago, several molecular and structural studies have unveiled and refined our understanding of Trn1-mediated nuclear import. In particular, the understanding at a molecular level of the NLS recognition by Trn1 made a decisive step forward with the identification of a new class of NLSs called PY-NLSs, which constitute the best-characterized substrates of Trn1. Besides PY-NLSs, many Trn1 cargoes harbour NLSs that do not resemble the archetypical PY-NLS, which complicates the global understanding of cargo recognition by Trn1. Although PY-NLS recognition is well established and supported by several structures, the recognition of non-PY-NLSs by Trn1 is far less understood, but recent reports have started to shed light on the recognition of this type of NLSs. Aside from its principal and long-established activity as a nuclear import receptor, Trn1 was shown more recently to moonlight outside nuclear import. Trn1 has for instance been caught in participating in virus uncoating, ciliary transport and in modulating the phase separation properties of aggregation-prone proteins. Here, we focus on the structural and functional aspects of Trn1-mediated nuclear import, as well as on the moonlighting activities of Trn1.

Higher-order spatial organization of the genome into chromatin compartments (permissive and repressive), self-associating domains (TADs), and regulatory loops provides structural integrity and offers diverse gene regulatory controls. In particular, chromatin regulatory loops, which bring enhancer and associated transcription factors in close spatial proximity to target gene promoters, play essential roles in regulating gene expression. The establishment and maintenance of such chromatin loops are predominantly mediated involving CTCF and the cohesin machinery. In recent years, significant progress has been made in revealing how loops are assembled and how they modulate patterns of gene expression. Here we will discuss the mechanistic principles that underpin the establishment of three-dimensional (3D) chromatin structure and how changes in chromatin structure relate to alterations in gene programs that establish immune cell fate. [ABSTRACT FROM AUTHOR]

Polymerization of 3′,5′ cyclic guanosine monophosphate (3′,5′ cGMP) was previously reported to afford short RNA sequences from a plausible mildly activated prebiotic precursor in a non‐enzymatic and template‐free manner. In the current paper we analyze the reaction with PAGE as well as by infrared micro‐ and nanospectroscopy on time scales not considered before. We provide evidence that a preliminary oligomerization step in dry state allows for a continued synthesis of RNA oligomers even in the presence of subsequently added water. On a longer time scale, the oligomerization yield oscillates in an apparently chaotic fashion hinting at the importance of some non‐reversible phase‐separation processes on the experimentally observed outcome of the polymerization/degradation chemistries. The long‐lasting (hundreds of hours) intrinsic sustainability and resilience of the process gives a robust prebiotic potential to this unique oligomerization reaction, which could lead to the very first oligonucleotide sequences on the primordial Earth. [ABSTRACT FROM AUTHOR]

Protein clustering plays numerous roles in cell physiology and disease. However, protein oligomers can be difficult to detect because they are often too small to appear as puncta in conventional fluorescence microscopy. Here, we describe a fluorescent reporter strategy that detects protein clusters with high sensitivity called CluMPS (clusters magnified by phase separation). A CluMPS reporter detects and visually amplifies even small clusters of a binding partner, generating large, quantifiable fluorescence condensates. We use computational modeling and optogenetic clustering to demonstrate that CluMPS can detect small oligomers and behaves rationally according to key system parameters. CluMPS detected small aggregates of pathological proteins where the corresponding GFP fusions appeared diffuse. CluMPS also detected and tracked clusters of unmodified and tagged endogenous proteins, and orthogonal CluMPS probes could be multiplexed in cells. CluMPS provides a powerful yet straightforward approach to observe higher-order protein assembly in its native cellular context. A record of this paper's transparent peer review process is included in the supplemental information., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

nArgBP2, a protein whose disruption is implicated in intellectual disability, concentrates in excitatory spine-synapses. By forming a triad with GKAP and SHANK, it regulates spine structural rearrangement. We here find that GKAP and SHANK3 concentrate close to the synaptic contact, whereas nArgBP2 concentrates more centrally in the spine. The three proteins collaboratively form biomolecular condensates in living fibroblasts, exhibiting distinctive layered localizations. nArgBP2 concentrates in the inner phase, SHANK3 in the outer phase, and GKAP partially in both. Upon co-expression of GKAP and nArgBP2, they evenly distribute within condensates, with a notable peripheral localization of SHANK3 persisting when co-expressed with either GKAP or nArgBP2. Co-expression of SHANK3 and GKAP with CaMKIIα results in phase-in-phase condensates, with CaMKIIα at the central locus and SHANK3 and GKAP exhibiting peripheral localization. Additional co-expression of nArgBP2 maintains the layered organizational structure within condensates. Subsequent CaMKIIα activation disperses a majority of the condensates, with an even distribution of all proteins within the extant deformed condensates. Our findings suggest that protein segregation via phase separation may contribute to establishing layered organization in dendritic spines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee and Chang.)

Aluminium-Titanium–Zinc mixed-metal-oxide system was investigated in order to elucidate appropriate sorbent material for the High-Temperature Gas-Desulphurisation (HTGD) in the Integrated Gasification Combined Cycle (IGCC). Conceptually, Zn-based constituent phases support sorption functionality, Ti-based constituent phases support chemical stability and Al-based constituent phases support mechanical durability. Samples were prepared using sol-gel synthesis in a broad compositional range from gahnite to Zn-titanate spinel; i.e. gahnite was Ti-doped on the account of Al (0–100%). Complexing agent was used to control the hydrolysis rate. We monitored the thermal and structural evolution in order to observe and clarify different mechanisms of phase formation, as a function of the doping and temperature conditions. The significance of this work lies within insight in the stability ranges of the observed solid-solutions, whereas gahnite spinel and zinc titanate spinels can interchange cations only in limited amounts, depending on the conditions, as confirmed from the structure refinement. It was observed that these solid-solution phases exhibit quite different stability when thermally treated. More importantly, observed partial phase-separation at low-temperature thermal treatment (which occur on behalf of different hygroscopic properties of the (Al,Ti)–Zn gels) significantly precludes the mechanisms of phase development at high-temperatures. Thereof, intermediate Zn-based phase was found to be responsible for the facilitated early zincite crystallisation. Microstructural and textural changes were correlated according to structural changes. Characterisation results allowed understanding of compositional and treatment conditions necessary for the selection of sorbent best with best functionality. • Desulphurisation sorbents were prepared in the Al–Ti–Zn mixed-metal-oxide system. • Sorbents are sol-gel derived gahnite Ti-doped on the account of Al (0–100%). • Gels resemble partial phase-separation that strongly precludes phases-development. • Different hygroscopies of the (Al,Ti)–Zn gels cause the partial phase-separation. • (Micro)Structure, specific surface, etc. nominate best sorbent treatment & doping. [ABSTRACT FROM AUTHOR]

While the important functions of long noncoding RNAs (lncRNAs) in nuclear organization are well documented, their orchestrating and architectural roles in the cytoplasmic environment have long been underestimated. However, recently developed fractionation and proximity labelling approaches have shown that a considerable proportion of cellular lncRNAs is exported into the cytoplasm and associates nonrandomly with proteins in the cytosol and organelles. The functions of these lncRNAs range from the control of translation and mitochondrial metabolism to the anchoring of cellular components on the cytoskeleton and regulation of protein degradation at the proteasome. In the present review, we provide an overview of the functions of lncRNAs in cytoplasmic structures and machineries und discuss their emerging roles in the coordination of the dense intracellular milieu. It is becoming apparent that further research into the functions of these lncRNAs will lead to an improved understanding of the spatiotemporal organization of cytoplasmic processes during homeostasis and disease. [ABSTRACT FROM AUTHOR]

Polymer electrolyte membrane fuel cell (PEMFC) is an eco-friendly energy conversion device that can convert chemical energy into electrical energy without emission of harmful oxidants such as nitrogen oxides (NOx) and/or sulfur oxides (SOx) during operation. Nafion®, a representative perfluorinated sulfonic acid (PFSA) ionomer-based membrane, is generally incorporated in fuel cell systems as a polymer electrolyte membrane (PEM). Since the PFSA ionomers are composed of flexible hydrophobic main backbones and hydrophilic side chains with proton-conducting groups, the resulting membranes are found to have high proton conductivity due to the distinct phase-separated structure between hydrophilic and hydrophobic domains. However, PFSA ionomer-based membranes have some drawbacks, including high cost, low glass transition temperatures and emission of environmental pollutants (e.g., HF) during degradation. Hydrocarbon-based PEMs composed of aromatic backbones with proton-conducting hydrophilic groups have been actively studied as substitutes. However, the main problem with the hydrocarbon-based PEMs is the relatively low proton-conducting behavior compared to the PFSA ionomer-based membranes due to the difficulties associated with the formation of well-defined phase-separated structures between the hydrophilic and hydrophobic domains. This study focused on the structural engineering of sulfonated hydrocarbon polymers to develop hydrocarbon-based PEMs that exhibit outstanding proton conductivity for practical fuel cell applications.

Two diketopyrrolopyrrole dimers with different oligomethylene tether length showed distinct aggregation behaviours, leading to a significant difference in the degree of phase separation upon mixing with PC61BM. Despite almost same optical properties, their blend films with PC61BM exhibited distinct power conversion efficiency in bulk‐heterojunction solar cells as a result of difference in phase separation. [ABSTRACT FROM AUTHOR]

Vapor co-deposited metal nanocomposites with immiscible components have shown to have several superior properties including mechanical performance, radiation tolerance, and enhanced functionalities. The morphology and structural design of these nanocomposites are important in determining the expression of these properties. The conditions used to deposit thin film nanocomposites are the governing factors in determining the final nanostructure. In this work, we link the effects of process gas pressure, substrate temperature, and sputtering target power on resultant Cu/Nb thin film nanostructures. We find that for films with equiatomic phase fractions of Cu and Nb, inhomogeneous precipitate segregation dominated the structure at lower substrate temperature depositions while higher temperatures distributed the Cu and Nb phases more uniformly. Increasing process gas pressure during deposition lead to a spatially homogeneous, nanocrystalline structure of Cu/Nb. In situ annealing of this sample shows that the phase separated morphology of the two immiscible materials depends on the initial composition. Finally, compositions of Cu and Nb that were highly disparate lead to interface segregation of the minority phase. The morphological evolution observed in the Cu/Nb system is compatible with modified structural zone models for immiscible thin film systems. • Substrate temperatures above 100 °C led to inhomogeneous Cu/Nb segregation. • Increasing process pressure allowed a homogeneous structure of Cu/Nb to dominate. • Highly concentrated compositions drove interface segregation. [ABSTRACT FROM AUTHOR]

Double-strand breaks (DSBs) are the most severe type of DNA damage. Previously, we demonstrated that RNA polymerase II (RNAPII) phosphorylated at the tyrosine 1 (Y1P) residue of its C-terminal domain (CTD) generates RNAs at DSBs. However, the regulation of transcription at DSBs remains enigmatic. Here, we show that the damage-activated tyrosine kinase c-Abl phosphorylates hSSB1, enabling its interaction with Y1P RNAPII at DSBs. Furthermore, the trimeric SOSS1 complex, consisting of hSSB1, INTS3, and c9orf80, binds to Y1P RNAPII in response to DNA damage in an R-loop-dependent manner. Specifically, hSSB1, as a part of the trimeric SOSS1 complex, exhibits a strong affinity for R-loops, even in the presence of replication protein A (RPA). Our in vitro and in vivo data reveal that the SOSS1 complex and RNAPII form dynamic liquid-like repair compartments at DSBs. Depletion of the SOSS1 complex impairs DNA repair, underscoring its biological role in the R-loop-dependent DNA damage response. [Display omitted] • Double-strand breaks (DSBs) are the most severe type of DNA damage • c-Abl phosphorylates hSSB1 (SOSS1), enabling its interaction with Y1P RNAPII at DSBs • The trimeric SOSS1 complex is present at DSBs in an R-loop-dependent manner • The SOSS1 complex and RNAPII form dynamic liquid-like repair compartments at DSBs Double-strand breaks (DSBs) are the most severe type of DNA damage. Long et al. show that hSSB1 is modified and forms a trimeric SOSS1 complex that comes to DSBs in an R-loop-dependent manner. At DSBs, SOSS1 and RNA polymerase II form liquid-like repair compartments. Depletion of the SOSS1 impairs DNA repair. [ABSTRACT FROM AUTHOR]

Objectives: Methacrylamides are proposed as components for dental adhesive systems with enhanced resistance to hydrolytic and enzymatic degradation. The specific objective of this study was to evaluate the polymerization kinetics, water sorption and solubility, pH-derived degradation and microtensile bond strength of various monofunctional acrylamides and meth(acrylamides) when copolymerized with dimethacrylates. Methods: Base monomers were added at 60 wt%, and included either BisGMA or UDMA. Monofunctional monomers were added at 40 wt%, including one (meth)acrylate as the control, two secondary methacrylamides and two tertiary acrylamides. DMPA (0.2 wt%) and DPI-PF6 (0.4 wt%)/BHT (0.1 wt%) were added as initiators/inhibitor. Polymerization kinetics wwere followed with near-IR spectroscopy in real time. Water sorption (WS) and solubility (SL) were measured following ISO 4049. Monomer degradation at different pH levels was assessed with 1H NMR. Microtensile bond strength (MTBS) was assessed in caries-free human third molars 48 h and 3 weeks after restorations were placed using solvated BisGMA-based adhesives (40 vol% ethanol). Data were analyzed with one-way ANOVA/Tukey's test (α = 0.05). Results: As expected, rate of polymerization and final degree of conversion (DC) were higher for the acryl versions of each monomer, and decreased with increasing steric hindrance around the vinyl group for each molecule. In general, UDMA copolymerizations were more rapid and extensive than for BisGMA, but this was dependent upon the specific monofunctional monomer added. WS/SL were in general higher for the (meth)acrylamides compared to the (meth)acrylates, except for the tertiary acrylamide, which showed the lowest values. One of the secondary methacrylamides was significantly more stable than the methacrylate control, but the alpha substitutions decreased stability to degradation in acid pH. MTBS in general was higher for the (meth)acrylates. While for all materials the MTBS values at 3 weeks decreased in relation to the 24 h results, the tertiary acrylamide showed no reduction in bond strength. Significance: This study highlights the importance of considering steric and electronic factors when designing monomers for applications where rapid polymerizations are needed, especially when co-polymerizations with other base monomers are required to balance mechanical properties, as is the case with dental adhesives. The results of this investigation will be used to design fully formulated adhesives to be tested in clinically-relevant conditions. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • High-performance, flexible and renewable artificial muscle via cellulose/ ionic liquid electrolyte was developed. • The electrolyte layer by solution-phase separation behaved advantages in flexibility and ions transfer efficiency. • Electrochemical characterization revealed reasons for the improvement of actuators. Abstract A flexible nano-biocomposite artificial muscle based on a mesoporous renewable cellulose/ionic liquid (IL-Cel) electrolyte membrane with high porosity of 91.31% was developed in this paper. The IL-Cel electrolyte membrane, fabricated by a solution-phase separation process, exhibited absolute advantages in flexibility and ion transfer efficiency, so IL-Cel regenerated actuators exhibited significant enhancement in the deflection displacement and force, which were 4 and 2 times greater than traditional DMAC/Li-dissolved cellulose (Dm-Cel)-based actuators. Good flexibility (from the tensile test) and low surface resistance (within 100 Ω, from SEM) were also attained by actuators composed of an IL-Cel electrolyte membrane without regenerated substances (from FT-IR and XRD). Actuators with a solid-state electric double layer capacitor using multi-wall carbon nanotubes as electrodes and [Emim]Ac-Cel as the polymer electrolyte, exhibited the highest specific capacitance of 890 mF g−1 at 20 mV s−1, a lower internal resistance (0.098 Ω g−1) at range of 105 Hz–0.01 Hz, and the lowest power density (149 W kg−1) at 10 A g−1. Results indicated that cathode deflection was achieved by the action of van der Waals force and anion volumetric strain. These findings suggest that the developed mesoporous IL-Cel based actuators hold great promise in the further study of high-performance actuators. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Polymerization-induced phase separation is used to fabricate Janus particles. • Cauliflower-like and dumbbell-like structures are obtained. • Fabricated particles are used to simultaneously carry both DOX and ibuprofen. Abstract Most recent studies on Janus particles have concentrated on amphiphilic Janus particles. Herein, a facile and efficient method based on polymerization-induced phase separation is presented to fabricate Janus particles with different morphologies. Theses novel hydrophilic Janus particles with two distinct hydrophilic domains have been prepared by combination of distillation precipitation polymerization (DPP) and seeded emulsion polymerization. Crosslinked poly(2-hydroxyehtyl methacrylate) (PHEMA) cores were synthesized via DPP and used as seed particles. Also, methacrylic acid (MAA) was used as second hydrophilic monomer. Effect of feeding approach, and reaction medium were investigated on the morphology of fabricated composite particles. Different morphologies such as cauliflower-like, dumbbell-like, and core-shell toward cauliflower-like structures were obtained by varying feeding approach and polymerization medium. The morphology of resultant particles was observed by means of FE-SEM and TEM images and their particle sizes were confirmed by DLS. Fabricated composite particles were used to simultaneously carry both DOX and ibuprofen. Drug release studies showed that Janus particles can be used in loading and release of two drugs simultaneously. However, release behaviors of DOX and ibuprofen were different at different pH values. Also, release behavior was significantly affected by the structure of composite particles. [ABSTRACT FROM AUTHOR]

Abstract In arid and water-deficient areas, contaminants on solar panels seriously affect the conversion efficiency of solar cells, since they are not removed by rainwater. This study introduces a superhydrophobic silica surface with special self-cleaning characteristics. Even in arid areas, dust on the surface is removed autonomously via the departure of dew drops: the self-jumping behavior of drops dramatically improves the dedusting efficiency and cleans the surface in a short time. This coating is prepared via a unique method in which interpenetrating nanosized silica pores are formed in sodium borosilicate glass. After surface modification, the treated glass has higher light transmission and better superhydrophobic and oleophobic properties, and subsequent heat treatment ensures good mechanical stability. We investigated different scenarios for particle removal from surfaces via condensate self-jumping for different particle numbers, sizes and types. The results provide new ideas and insights into the application of self-cleaning materials in optical instruments. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Activated carbon monolith with a co-continuous porous structure was fabricated. • Polyacrylonitrile (PAN)/bacterial cellulose (BC) monolith was used as precursor. • BC nanofibers entwined in porous PAN skeleton gives continuous carbon matrix. • Grain boundary impedance is very small even without external conductive agent. • Good electrode material for EDLC with high-speed charge/discharge capability. Abstract Bacterial cellulose (BC) gel is synthesized by static culture process at the interface between air and medium. The solvent-exchanged BC gel is incorporated into polyacrylonitrile (PAN) copolymer solution under heating at 90 °C and subsequent cooling gives bacterial cellulose-polyacrylonitrile composite (BC-PAN) monolith. The BC-PAN monolith is carbonized at 1000 °C with physical activation in the presence of CO 2 to obtain the activated carbon monolith, BC-PAN-AC , with large surface area and high microporosity. Unique morphologies are observed for BC gel which is propagated to the BC-PAN monolith and restored in BC-PAN-AC. The BC nanofibers remain entwined throughout the porous skeleton of the PAN backbone and the entangled structure helps in retaining the continuity of the matrix of BC-PAN-AC and reduce the grain boundary impedance for electrical conduction. Cyclic voltammetry shows that these activated carbons are good electrode materials in electric double layer capacitors (EDLC) with capability of high-speed charging and discharging. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Simple binary mixtures of hydrogenated and perfluorinated surfactants are typically immiscible in monolayers, with mixtures forming highly-structured films at the air-water and solid-air interfaces. While dispersion interactions between tail groups of the surfactants play a key role in dictating the micron-scale morphology of such mixed films, the influence of the head group on film morphology has been minimally explored. In this work, surfactant head group effects are investigated by comparing thermodynamic miscibility in combination with film morphology in binary mixed films comprised of nonadecanoic acid (ND; CH 3 (CH 2) 17 COOH) with perfluorotetradecanoic acid (PF; CF 3 (CF 2) 12 COOH), as well as the corresponding fatty alcohol nonadecanol (NDOH; CH 3 (CH 2) 18 OH) with PF. Both the fatty acid and fatty alcohol were immiscible with PF in monolayers, with the systems exhibiting small, negative deviations from ideal mixing and forming phase-separated domains under a variety of preparation conditions. Micron and nanometer-scale film morphologies for the two sets of films were significantly different, however, with fatty acid mixtures tending to form polygonal, faceted domains enriched in hydrocarbon whereas the fatty alcohol mixtures formed significantly less structured domains, both at the solid- and liquid-air interfaces. Differences in film morphologies are discussed in terms of head and tail group interactions, and placed in context of existing literature on closely-related monolayer systems. [ABSTRACT FROM AUTHOR]

A conventional planar InGaN/GaN multiple quantum well (MQW)-based light emitting diode (LED) producing a blue-green dual-wavelength spectrum, due to phase separation in the InGaN well layers, is grown, and fabricated into a nanopillar (NP) LED array structure with an etching depth penetrating through the MQW region using a top-down dry etching process. Excitation power and temperature dependences of the photoluminescence (PL) spectra of the planar and NP samples have shown that the fabrication of the nanotexture not only decreases the quantum-confined Stark effect (QCSE), but also enhances the carrier localisation effect, both in the InGaN matrix region and in the In-rich quasi-quantum dot (QD) region, due to the reduction of the strain relaxation-induced piezoelectric field in the MQWs embedded in the nanopillars. Moreover, the fabrication of the nanotexture also improves the light extraction efficiency (LEE), due to the increased light-extracting surface area and light-guiding effect. These results are also consistent with the measured quantum efficiencies of the two samples. [ABSTRACT FROM AUTHOR]

The gelation mechanism of agarose solution on cooling has been successfully elucidated by measurements from macroscopic to microscopic scales using a dynamic rheometer, the multiple particle tracking with two different diameters and the pulsed-field-gradient stimulated echo (PGSTE) 1H NMR. The dynamic rheometer detected the gradual increase of G ' in the temperature range from 55 to 40 °C before the steep increase at the gelation temperature. The time-averaged mean square displacement (msd) obtained by multiple particle tracking for particles with diameter of 270 nm and 1000 nm revealed the generation of micro domains with the network structure obstructing particle diffusion. Further, the NMR measurements gave detailed information about the change of molecular mobility for agarose chains during the formation of the micro domains and the macroscopic overall network structure. These results suggest a gelation mechanism and gel network structure including the formation of micro domains in the temperature range from 55 to 40 °C and the connection among the micro domains by agarose aggregates to form the overall network structure at the gelation temperature. [Display omitted] • Particle tracking detected the formation of micro domain of network before gelation. • Particles with different sizes were used to elucidate the network structure with different length scale. • Gradient NMR gave the information about the formation of aggregates during gelation. [ABSTRACT FROM AUTHOR]

It is widely, but not universally, believed that the lipids of the plasma membrane are not uniformly distributed, but that “rafts” of sphingolipids and cholesterol float in a “sea” of unsaturated lipids. The physical origin of such heterogeneities is often attributed to a phase coexistence between the two different domains. We argue that this explanation is untenable for several reasons. Further, we note that the results of recent experiments are inconsistent with this picture. However, they are quite consistent with an alternate explanation, namely, that the plasma membrane is a microemulsion of the two kinds of regions. To show this, we briefly review a simplified version of this theory and its phase diagram. We also explicate the dependence of the predicted domain size on four physical parameters. They are the energy cost of gradients in the composition, the spontaneous curvature of the membrane, its bending modulus and its surface tension. Taking values of the latter two from experiment, we obtain domain sizes for several different cell types that vary from 58 to 88 nm.