Sequential Domains Research Articles

Structure and evolution of metapolycentromeres.

Metapolycentromeres consist of multiple sequential domains of centromeric chromatin associated with a centromere-specific variant of histone H3 (CENP-A), functioning collectively as a single centromere. To date, they have been revealed in nine flowering plant, five insect and six vertebrate species. In this paper, we focus on their structure and possible mechanisms of emergence and evolution. The metapolycentromeres may vary in the number of centromeric domains and in their genetic content and epigenetic modifications. However, these variations do not seem to affect their function. The emergence of metapolycentromeres has been attributed to multiple Robertsonian translocations and segmental duplications. Conditions of genomic instability, such as interspecific hybridization and malignant neoplasms, are suggested as triggers for the de novo emergence of metapolycentromeres. Addressing the "centromere paradox" - the rapid evolution of centromeric DNA and proteins despite their conserved cellular function - we explore the centromere drive hypothesis as a plausible explanation for the dynamic evolution of centromeres in general, and in particular the emergence of metapolycentromeres and holocentromeres. Apparently, metapolycentromeres are more common across different species than it was believed until recently. Indeed, a systematic review of the available cytogenetic publications allowed us to identify 27 candidate species with metapolycentromeres. Тhe list of the already established and newly revealed candidate species thus spans 27 species of flowering plants and eight species of gymnosperm plants, five species of insects, and seven species of vertebrates. This indicates an erratic phylogenetic distribution of the species with metapolycentromeres and may suggest an independent emergence of the metapolycentromeres in the course of evolution. However, the current catalog of species with identified and likely metapolycentromeres remains too short to draw reliable conclusions about their evolution, particularly in the absence of knowledge about related species without metapolycentromeres for comparative analysis. More studies are necessary to shed light on the mechanisms of metapolycentromere formation and evolution.

A census of actin-associated proteins in humans.

Actin filaments help in maintaining the cell structure and coordinating cellular movements and cargo transport within the cell. Actin participates in the interaction with several proteins and also with itself to form the helical filamentous actin (F-actin). Actin-binding proteins (ABPs) and actin-associated proteins (AAPs) coordinate the actin filament assembly and processing, regulate the flux between globular G-actin and F-actin in the cell, and help maintain the cellular structure and integrity. We have used protein-protein interaction data available through multiple sources (STRING, BioGRID, mentha, and a few others), functional annotation, and classical actin-binding domains to identify actin-binding and actin-associated proteins in the human proteome. Here, we report 2482 AAPs and present an analysis of their structural and sequential domains, functions, evolutionary conservation, cellular localization, abundance, and tissue-specific expression patterns. This analysis provides a base for the characterization of proteins involved in actin dynamics and turnover in the cell.

AAV9 gene transfer of N-terminal truncated cMyBPC ameliorates cardiac function in cMyBPC-deficient mice.

Cardiac myosin binding protein C (cMyBPC) is a sarcomeric protein made up of 11 sequential domains (C0-C10) integral to regulation of cardiac muscle. The N-terminal portion of the molecule has been extensively studied and is known to play a key role in cMyBPC's ability to modulate cardiac function. Studies show that AAV9-driven cardiac expression of C0C2 is sufficient to ameliorate cardiac function in cMyBPC-/- mice. Cardiac function in cMyBPC-/- mice is characterized by hypercontractile cross-bridge kinetics at the sarcomere level, which translates to truncated ejection time at the organ level. C0C2 expression normalizes hypercontractile cross-bridge kinetics and prolongs ejection time, thereby increasing ejection fraction. In contrast to the N-terminus, relatively little is known about the functional relevance of the remainder of the cMyBPC molecule. Recent in vitro studies have demonstrated a potential role for cMyBPC regions outside of the N-terminus in modulation of molecular structure and function. However, the contributions of these domains to in vivo function have yet to be fully explored. In this study, we examine the in vivo consequences of expression of N-terminal truncated cMyBPC, i.e., C3C10. We used AAV9 to drive cardiac expression of C3C10 or full-length cMyBPC in cMyBPC-/- mice. Neonatal mice were injected, and echocardiography was performed 6 weeks post-injection to evaluate cardiac structure and function. The presence of AAV9-delivered constructs was verified by Western Blot, and localization within the sarcomere was confirmed by immunohistochemistry. Our results show that in vivo incorporation of cMyBPC domains C3C10 into the sarcomere improves function and contributes to normalization of cardiac morphology, however, does not alter ejection time. Our findings suggest that other domains of cMyBPC contribute to regulation of cardiac function in vivo by mechanisms distinct from those attributable to N-terminal domains.

Appropriateness of the dialysis modality selection process: A cross-sectional study.

Studies that specifically quantify the appropriateness of the process of dialysis modality selection are lacking. Peritoneal dialysis (PD) offers clinical and social advantages over hemodialysis (HD), but may be underused. We aimed to determine the appropriateness of the process of dialysis modality selection and quantify the percentage of patients who could potentially have been PD candidates. We performed a cross-sectional study that included adult patients from a hospital Nephrology Department in Barcelona who started dialysis between 2014 and 2015. We assessed the appropriateness of dialysis modalities selection by defining 3 sequential domains based on 3 critical steps in choosing a dialysis modality: eligibility for either treatment, information about modalities, and shared decision-making. We obtained data using medical records and a patient questionnaire. The dialysis modality selection process was considered appropriate when patients had no contraindications for the selected option, received complete information about both modalities, and voluntarily chose the selected option. A total of 141 patients were included in this study. The median age was 72 years (interquartile range 63–82 years), and 65% of the patients were men. The dialysis modality selection process was potentially inappropriate in 22% of the participants because of problems related to information about dialysis modalities (15%) or shared decision-making (7%). Appropriate PD use can potentially increase from 17% to 38%. Patient age and lack of information regarding dialysis options were independently associated with the potential degree of inappropriate dialysis modality selection. Our findings indicate areas for improvement in the selection of dialysis modalities. With better education and shared decision-making, the number of patients with PD could potentially double. The analysis of appropriateness is a helpful approach for studying renal replacement treatment patterns and identifying strategies to optimize their use.

Effect of the Janus Amphiphilic Wall on the Viscosity Behavior of Aqueous Surfactant Solutions

The effects of the chemical nature of an interface are one of the key parameters which can affect self-assembly and rheological behavior. To date, several studies have reported self-assembled structures and rheological behaviors in the development of various functional materials. In this study, we investigated the self-assembly and viscosity behavior of aqueous surfactant solutions confined in three types of Janus amphiphilic nanotubes (JANTs), which have two, four, and eight sequential domains, respectively, using molecular simulation. We found that the viscosity behavior depends on the surfactant concentration and the chemical nature of the wall surface. For instance, although the concentration levels of the surfactants are the same (c = 10%), completely different viscosity behaviors were observed in the two sequential domains (Newtonian-like) and the four and eight sequential domains (strong shear-thinning) of the JANTs. Our simulations demonstrated how the rheological properties of aqueous surfactant solutions, including viscosity and velocity profiles, can be controlled by the chemical nature of the JANT wall surface, effect of confinement, and their self-assembly structures. Considering the foregoing, we hope that our study offers new knowledge on nanofluid systems.

Chimera states formed via a two-level synchronization mechanism

We introduce an oscillatory toy-model with variable frequency governed by a 3rd order equation to shed light on the formation of chimera states in systems of coupled oscillators. The toy-oscillators are constructed as bistable units and depending on the initial conditions their frequency may result in one of the two attracting fixed points, and (two-level synchronization). Numerical simulations demonstrate that when these oscillators are nonlocally coupled in networks, they organize in domains with alternating frequencies. In each domain the oscillators synchronize, while sequential domains follow different modes of synchronization. The border elements between two consecutive domains form the asynchronous domains as they are influenced by both frequencies. This way chimera states are formed via a two-level synchronization scenario. We investigate the influence of the frequency coupling constant and of the coupling range on the chimera morphology and we show that the chimera multiplicity decreases as the coupling range increases.The frequency spectrum is calculated in the coherent and incoherent domains of this model. In the coherent domains single frequencies ( or ) are observed, while in the incoherent domains both and as well as their superpositions appear. This mechanism of creating domains of alternating frequencies offers a reasonable generic scenario for chimera state formation.

Multiobjective model-free learning for robot pathfinding with environmental disturbances

This article addresses the robot pathfinding problem with environmental disturbances, where a solution to this problem must consider potential risks inherent in an uncertain and stochastic environment. For example, the movements of an underwater robot can be seriously disturbed by ocean currents, and thus any applied control actions to the robot cannot exactly lead to the desired locations. Reinforcement learning is a formal methodology that has been extensively studied in many sequential decision-making domains with uncertainty, but most reinforcement learning algorithms consider only a single objective encoded by a scalar reward. However, the robot pathfinding problem with environmental disturbances naturally promotes multiple conflicting objectives. Specifically, in this work, the robot has to minimise its moving distance so as to save energy, and, moreover, it has to keep away from unsafe regions as far as possible. To this end, we first propose a multiobjective model-free learning framework, and then proceed to investigate an appropriate action selection strategy by improving a baseline with respect to two dimensions. To demonstrate the effectiveness of the proposed learning framework and evaluate the performance of three action selection strategies, we also carry out an empirical study in a simulated environment.

Extracting mutual exclusion invariants from lifted temporal planning domains

We present a technique for automatically extracting mutual exclusion invariants from temporal planning instances. It first identifies a set of invariant templates by inspecting the lifted representation of the domain and then checks these templates against properties that assure invariance. Our technique builds on other approaches to invariant synthesis presented in the literature but departs from their limited focus on instantaneous actions by addressing temporal domains. To deal with time, we formulate invariance conditions that account for the entire temporal structure of the actions and the possible concurrent interactions between them. As a result, we construct a more comprehensive technique than previous methods, which is able to find not only invariants for temporal domains but also a broader set of invariants for sequential domains. Our experimental results provide evidence that our domain analysis is effective at identifying a more extensive set of invariants, which results in the generation of fewer multi-valued state variables. We show that, in turn, this reduction in the number of variables reflects positively on the performance of the temporal planners that use a variable/value representation.

HRM frames of HR managers and line managers: congruence, consequences and context

In the HRM literature more and more attention is being paid to the role of HRM frames, especially in the phase of introducing new HRM sub-systems. Individual HRM frames consist of assumptions, expectations and knowledge about HRM. If individual HRM frames share common contents and structures, they are regarded as congruent. According to theory, congruent frames of different stakeholders increase the efficiency of the introduction of organisational changes. This study investigates the congruence of HRM frames between HR professionals and line managers in different European companies and industries by means of a qualitative analysis of 94 semi-structured interviews with HR professionals and line managers. The results suggest a model with four sequential domains: HRM-as-intended, HRM-as-composed, HRM-in-use and HRM-in-integration. This study contributes to the existing literature by exploring the importance of HRM frames during HR change, proposing a model that regards and explains HRM as a process.

HRM frames of HR managers and line managers: congruence, consequences and context

In the HRM literature more and more attention is being paid to the role of HRM frames, especially in the phase of introducing new HRM sub-systems. Individual HRM frames consist of assumptions, expectations and knowledge about HRM. If individual HRM frames share common contents and structures, they are regarded as congruent. According to theory, congruent frames of different stakeholders increase the efficiency of the introduction of organisational changes. This study investigates the congruence of HRM frames between HR professionals and line managers in different European companies and industries by means of a qualitative analysis of 94 semi-structured interviews with HR professionals and line managers. The results suggest a model with four sequential domains: HRM-as-intended, HRM-as-composed, HRM-in-use and HRM-in-integration. This study contributes to the existing literature by exploring the importance of HRM frames during HR change, proposing a model that regards and explains HRM as a process.

Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader.

The remarkable accuracy of eukaryotic cell division is partly maintained by the cohesin complex acting as a molecular glue to prevent premature sister chromatid separation. The loading of cohesin onto chromosomes is catalyzed by the Scc2-Scc4 loader complex. Here, we report the crystal structure of Scc4 bound to the N terminus of Scc2 and show that Scc4 is a tetratricopeptide repeat (TPR) superhelix. The Scc2 N terminus adopts an extended conformation and is entrapped by the core of the Scc4 superhelix. Electron microscopy (EM) analysis reveals that the Scc2-Scc4 loader complex comprises three domains: a head, body, and hook. Deletion studies unambiguously assign the Scc2N-Scc4 as the globular head domain, whereas in vitro cohesin loading assays show that the central body and the hook domains are sufficient to catalyze cohesin loading onto circular DNA, but not chromatinized DNA in vivo, suggesting a possible role for Scc4 as a chromatin adaptor.

Gestation of a Glu Plasminogen Supra Fold via Molecular Dynamics Simulation

Plasminogen (Pgn) is the precursor of plasmin, a proteinase that plays key roles in tissue remodeling, cell migration, fibrinolysis, etc. Pgn, Mr ∼92 kD, is structured by seven in-tandem globular domains: an N-terminal preactivation peptide (PAN, 77 aa), five kringle (K) repeats (∼ 80 aa each), and a trypsinogen-like serine protease zymogen (243 aa). Upon activation, Pgn undergoes a conformational change such that binding sites in kringles become accessible and able to interact with fatty acids and exposed lysyl side-chains. Via molecular dynamics (MD) simulations, we have investigated changes in inter-domain interactions that reflect supra-fold of Pgn. A model structure built by connecting sequential domains with fully extended flexible linkers was placed in a box of 282487 explicit water molecules and allowed to equilibrate for 420 ns via NAMD under CHARMM force field. During the MD, the protein folds as monitored by its radius of gyration (RG) that decreases from 157 A to 34 A, in good agreement with experimental observations (Mangel WF, Lin BH, Ramakrishnan V. Science 1990;248:69-73; Ponting CP, Holland SK, Cederholm-Williams SA, et al. Biochim Biophys Acta 1992;1159:155-161). The equilibrated structure is compact with a spiral spatial configurations of the in-tandem domains, as reported for the crystal (Law RHP, Caradoc-Davies T, Cowieson N, et al. Cell Reports 2012;1:185-190). By reversing the time course of the trajectory, dynamics insights are gained for the unfolding that accompanies the Pgn conformational change in the process of fibrinolysis. The PAN-K5 interaction was analyzed via free energy calculations as a function of relevant key inter-atomic distances. Two energy minima unveil configurations that exhibit strong and weak interactions between the PAN Lys 50 and the Asp516/Asp518 loci at the canonical K5 lysine binding site.

Decoding the components of dynamics in three‐domain proteins

In this study, we examine the feasibility and limitations of describing the motional behavior of three-domain proteins in which the domains are linearly connected. In addition to attempting the determination of the internal and overall reorientational correlation times, we investigate the existence of correlations in the motions between the three domains. Since in linearly arranged three-domain proteins, there are typically no experimental data that can directly report on motional correlation between the first and the third domain, we address this question by dynamics simulations. Two limiting cases occur: (1) for weak repulsive potentials and (2) when strong repulsive potentials are applied between sequential domains. The motions of the terminal domains become correlated in the case of strong interdomain repulsive potentials when these potentials do not allow the angle between the sequential domains to be smaller than about 60°. Using the model-free (MF) and extended MF formalisms of Lipari and Szabo, we find that the motional behavior can be separated into two components; the first component represents the concerted overall motion of the three domains, and the second describes the independent component of the motion of each individual domain. We find that this division of the motional behavior of the protein is maintained only when their timescales are distinct and can be made when the angles between sequential domains remain between 60° and 160°. In this work, we identify and quantify interdomain motional correlations.

Discovering putative prion sequences in complete proteomes using probabilistic representations of Q/N-rich domains

BackgroundPrion proteins conform a special class among amyloids due to their ability to transmit aggregative folds. Prions are known to act as infectious agents in neurodegenerative diseases in animals, or as key elements in transcription and translation processes in yeast. It has been suggested that prions contain specific sequential domains with distinctive amino acid composition and physicochemical properties that allow them to control the switch between soluble and β-sheet aggregated states. Those prion-forming domains are low complexity segments enriched in glutamine/asparagine and depleted in charged residues and prolines. Different predictive methods have been developed to discover novel prions by either assessing the compositional bias of these stretches or estimating the propensity of protein sequences to form amyloid aggregates. However, the available algorithms hitherto lack a thorough statistical calibration against large sequence databases, which makes them unable to accurately predict prions without retrieving a large number of false positives.ResultsHere we present a computational strategy to predict putative prion-forming proteins in complete proteomes using probabilistic representations of prionogenic glutamine/asparagine rich regions. After benchmarking our predictive model against large sets of non-prionic sequences, we were able to filter out known prions with high precision and accuracy, generating prediction sets with few false positives. The algorithm was used to scan all the proteomes annotated in public databases for the presence of putative prion proteins. We analyzed the presence of putative prion proteins in all taxa, from viruses and archaea to plants and higher eukaryotes, and found that most organisms encode evolutionarily unrelated proteins with susceptibility to behave as prions.ConclusionsTo our knowledge, this is the first wide-ranging study aiming to predict prion domains in complete proteomes. Approaches of this kind could be of great importance to identify potential targets for further experimental testing and to try to reach a deeper understanding of prions’ functional and regulatory mechanisms.

ECOMICS:Ecosystem Trans-OMICS Tools and Methods for Complex Environmental Samples and Datasets

Despite the apparent detachment of modern industrial societies from natural ecosystems, such systems continue to provide enormous and essential benefits in the form of ecosystem services, including potable water, clean air, and forest products and fisheries. Further, engineered ecosystems, but ecosystems nevertheless, provide the majority of agricultural and additional forestry products. Relationships between ecosystem services and human needs can be identified by connecting genomic information of component organisms with enzyme functions, metabolic pathways and resulting product chemicals such as biomass. Tools that advance the understanding of ecosystem function from the perspective of both environmental and metabolic systems are an important aspect of the emerging systems approach to biological science. We introduce here a web service designated “ECOMICS” to provide an omics approach to clarify such relationships. ECOMICS comprises the E-class web tool for taxonomic (metagenomic) classification based on prokaryotic and eukaryotic ribosomal sequences and selected functional (enzymatic) classification based on sequential domains, FT2DB for the digitization of NMR spectra for chemicals from metabolic to macromolecular phenotyping, Bm-Char for the chemical (macromolecular biomass) assignment of lignocellulose components, and HetMap for identifying and viewing correlations between heterogeneous trans-omics data sets that are produced by such web tools. This website is open to the public domain: https://database.riken.jp/ecomics/.

Fucose-binding Lectin from Opportunistic Pathogen Burkholderia ambifaria Binds to Both Plant and Human Oligosaccharidic Epitopes

Burkholderia ambifaria is generally associated with the rhizosphere of plants where it has biocontrol effects on other microorganisms. It is also a member of the Burkholderia cepacia complex, a group of closely related bacteria that cause lung infections in immunocompromised patients as well as in patients with granulomatous disease or cystic fibrosis. Our previous work indicated that fucose on human epithelia is a frequent target for lectins and adhesins of lung pathogens (Sulák, O., Cioci, G., Lameignère, E., Balloy, V., Round, A., Gutsche, I., Malinovská, L., Chignard, M., Kosma, P., Aubert, D. F., Marolda, C. L., Valvano, M. A., Wimmerová, M., and Imberty, A. (2011) PLoS Pathog. 7, e1002238). Analysis of the B. ambifaria genome identified BambL as a putative fucose-binding lectin. The 87-amino acid protein was produced recombinantly and demonstrated to bind to fucosylated oligosaccharides with a preference for αFuc1-2Gal epitopes. Crystal structures revealed that it associates as a trimer with two fucose-binding sites per monomer. The overall fold is a six-bladed β-propeller formed by oligomerization as in the Ralstonia solanacearum lectin and not by sequential domains like the fungal fucose lectin from Aleuria aurantia. The affinity of BambL for small fucosylated glycans is very high as demonstrated by microcalorimetry (K(D) < 1 μM). Plant cell wall oligosaccharides and human histo-blood group oligosaccharides H-type 2 and Lewis Y are bound with equivalent efficiency. Binding to artificial glycosphingolipid-containing vesicles, human saliva, and lung tissues confirmed that BambL could recognize a wide spectrum of fucosylated epitopes, albeit with a lower affinity for biological material from nonsecretor individuals.

A synthetic theory of sequential domains

Synthetic Domain Theory (SDT) was originally suggested by Dana Scott as a uniform and logic based account of domain theory. In SDT the domain structure is intrinsic to a chosen class of sets with “good” properties.General SDT has a lot of different models which differ w.r.t. the ambient logic but also w.r.t. the PCF hierarchy, i.e. the finite type hierarchy over the partial natural numbers. From the early days of SDT we know satisfactory axiomatizations of SDT à la Scott which enforce the existence of “parallel or”. A realizability model for SDT where the PCF hierarchy coincides with the strongly stable model of Bucciarelli and Ehrhard has been found independently by van Oosten (1999) [24] and Longley (2002) [13]. Their model is based on the typed partial combinatory algebra SA of concrete data structures and sequential algorithms.In this paper, we try to axiomatize this kind of Sequential SDT for the first time. Our approach is based on replacing SA by OSA, the observably sequential algorithms, as suggested by Cartwright et al. (1994) [3]. The axioms are inspired by the realizability model over OSA and its type O of observations with two global elements standing for nontermination and termination with error, respectively. Unlike in traditional domain theory this type is not a dominance because binary infimum is not available as an operation. This forces us to adapt some of the basic machinery of SDT.

Influence of glycosylation and oligomerization of vaccinia virus complement control protein on level and pattern of functional activity and immunogenicity

Vaccinia virus complement control protein (VCP) is one of the proteins encoded by vaccinia virus to modulate the host inflammatory response. VCP modulates the inflammatory response and protects viral habitat by inhibiting the classical and the alternative pathways of complement activation. The extended structure of VCP, mobility between its sequential domains, charge distribution and type of residues at the binding regions are factors that have been identified to influence its ability to bind to complement proteins. We report that a Lister strain of vaccinia virus encodes a VCP homolog (Lis VCP) that is functional, glycosylated, has two amino acids less than the well-characterized VCP from vaccinia virus WR strain (WR VCP), and the human smallpox inhibitor of complement enzymes (SPICE) from variola virus. The glycosylated VCP of Lister is immunogenic in contrast to the weak immunogenicity of the nonglycosylated VCP. Lis VCP is the only orthopoxviral VCP homolog found to be glycosylated, and we speculate that glycosylation influences its pattern of complement inhibition. We also correlate dimerization of VCP observed only in mammalian and baculovirus expression systems to higher levels of activity than monomers, observed in the yeast expression system.

The C. elegans Hox gene ceh-13 regulates cell migration and fusion in a non-colinear way. Implications for the early evolution of Hoxclusters

BackgroundHox genes play a central role in axial patterning during animal development. They are clustered in the genome and specify cell fate in sequential domains along the anteroposterior (A-P) body axis in a conserved order that is co-linear with their relative genomic position. In the soil worm Caenorhabditis elegans, this striking rule of co-linearity is broken by the anterior Hox gene ceh-13, which is located between the two middle Hox paralogs, lin-39 and mab-5, within the loosely organized nematode Hox cluster. Despite its evolutionary and developmental significance, the functional consequence of this unusual genomic organization remains unresolved.ResultsIn this study we have investigated the role of ceh-13 in different developmental processes, and found that its expression and function are not restricted to the anterior body part. We show that ceh-13 affects cell migration and fusion as well as tissue patterning in the middle and posterior body regions too. These data reveal novel roles for ceh-13 in developmental processes known to be under the control of middle Hox paralogs. Consistently, enhanced activity of lin-39 and mab-5 can suppress developmental arrest and morphologic malformation in ceh-13 deficient animals.ConclusionOur findings presented here show that, unlike other Hox genes in C. elegans which display region-specific accumulation and function along the A-P axis, the expression and functional domain of the anterior Hox paralog ceh-13 extends beyond the anterior region of the worm. Furthermore, ceh-13 and the middle Hox paralogs share several developmental functions. Together, these results suggest the emergence of the middle-group Hox genes from a ceh-13-like primordial Hox ancestor.

Molecular basis of cellular localization of poly C binding protein 1 in neuronal cells

Poly C binding protein 1 (PCBP) is involved in the transcriptional regulation of neuronal mu-opioid receptor gene. In this study, we examined the molecular basis of PCBP cellular/nuclear localization in neuronal cells using EGFP fusion protein. PCBP, containing three KH domains and a variable domain, distributed in cytoplasm and nucleus with a preferential nuclear expression. Domain-deletional analyses suggested the requirement of variable and KH3 domains for strong PCBP nuclear expression. Within the nucleus, a low nucleolar PCBP expression was observed, and PCBP variable domain contributed to this restricted nucleolar expression. Furthermore, the punctate nuclear pattern of PCBP was correlated to its single-stranded (ss) DNA binding ability, with both requiring cooperativity of at least three sequential domains. Collectively, certain PCBP domains thus govern its nuclear distribution and transcriptional regulatory activity in the nucleus of neurons, whereas the low nucleolar expression implicates the disengagement of PCBP in the ribosomal RNA synthesis.