Over the last decade, our appreciation of the importance of the nucleolus for cellular function has progressed from the ordinary to the extraordinary. We no longer think of the nucleolus as simply the site of ribosome production, or a dynamic subnuclear body noted by pathologists for its changes in size and shape with malignancy. Instead, the nucleolus has emerged as a key controller of many cellular processes that are fundamental to normal cell homeostasis and the target for (...) dysregulation in many human diseases; in some cases, independent of its functions in ribosome biogenesis. These extra‐nucleolar or new functions, which we term “non‐canonical” to distinguish them from the more traditional role of the nucleolus in ribosome synthesis, are the focus of this review. In particular, we explore how these non‐canonical functions may provide novel insights into human disease and in some cases new targets for therapeutic development. (shrink)

The mammalian oocyte is a round cell arrested at prophase I of meiosis. It is characterized by the presence of a large nucleus, called the germinal vesicle, in the middle of which is the nucleolus. Before it can be fertilized, the oocyte must resume meiosis, enter metaphase II and be ovulated. The nucleolus is dissolved during this process. However, the nucleoli of the male and female pronuclei in the zygote are both of maternal origin. A recent paper1 demonstrates (...) that the maternal nucleolus, together with other nucleoplasmic elements, is essential for early embryonic development. These nucleolar and nucleoplasmic factors remain undetermined. BioEssays 30:613–616, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The nucleolus is a region of the nucleus with high protein density and it acts as a ribosome factory. The nucleolus contains a distinct region of the genome, the ribosomal RNA gene repeats (rDNA) that supply ribosomal RNA (rRNA) molecules. The rDNA is the most‐abundant gene and occupies a large part of the genome, for example, there are thousands of rDNA copies in the genomes of plant cells. Therefore, it is natural to suppose that the condition of the (...) rDNA, such as its stability, might affect cellular functions. Here I would like to propose a new model regarding the roles of the rDNA and nucleolus. The key point of this model is that they act to preserve genome stability and trigger aging. BioEssays 30:267–272, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Nucleoli are the sites of ribosome biogenesis. Transcription of the ribosomal RNA genes as well as processing and initial packaging of their transcripts with ribosomal and non‐ribosomal proteins all occur within the nucleolus in an ordered manner and under defined topological conditions. Components of the nucleolus have been localized by immunocytochemistry and their functional aspects investigated by microinjection of antibodies directed against the enzyme responsible for rDNA transcription, RNA polymerase I. The role of nascent transcripts in postmitotic formation (...) of nucleoli will be discussed. (shrink)

The nucleolus may represent a key stress response organelle in the nucleus following proteotoxic stress by serving as a platform for protein aggregates. Aggregation of proteins often results from insufficient protein degradation by the ubiquitin‐proteasome system (UPS), occurring in inclusion diseases, upon treatment by proteasome inhibitors (PIs) or due to various forms of stress. As the nucleolar inclusions resemble cytoplasmic aggresomes in gathering ubiquitin and numerous UPS components and targets, including cancer‐related transcription factors and cell cycle regulators (e.g. p53 (...) and cyclin D) and proteins involved in neurodegenerative diseases (e.g. ataxin‐1, Malin), these organelles are termed herein as nucleolar aggresomes. These nucleolar aggresomes contain polyadenylated RNA, and seem to be linked to defects in nuclear export. Nucleolar aggresomes have been identified in non‐neuronal cells, but prominent similarities with nuclear ubiquitin and/or ribonuclear foci detected in triplet and other repeat disease pathologies are revealed here, creating a common interest between research in cancer and neurodegeneration. (shrink)

A community faces the obligation of providing an indivisible public good that each of its members is able to provide at a certain cost. The solution is to rely on the member who can provide the public good at the lowest cost, with a due compensation from the other members. This problem has been studied in a non-cooperative setting by Kleindorfer and Sertel. They propose an auction mechanism that results in an interval of possible individual contributions whose lower bound is (...) the equal division. Here, instead we take a cooperative stand point by modelling this problem as a cost sharing game that turns out to be a ‘reverse’ airport game whose core is shown to have a regular structure. This enables an easy calculation of the nucleolus that happens to define the upper bound of the Kleindorfer–Sertel interval. The Shapley value instead is not an appropriate solution in this context because it may imply compensations to non-providers. (shrink)

The Choquet expected utility model deals with nonadditive probabilities (or capacities). Their dependence on the information the decision-maker has about the possibility of the events is taken into account. Two kinds of information are examined: interval information (for instance, the percentage of white balls in an urn is between 60% and 100%) and comparative information (for instance, the information that there are more white balls than black ones). Some implications are shown with regard to the core of the capacity and (...) to two additive measures which can be derived from capacities: the Shapley value and the nucleolus. Interval information bounds prove to be satisfied by all probabilities in the core, but they are not necessarily satisfied by the nucleolus (when the core is empty) and the Shapley value. We must introduce the constrained nucleolus in order for these bounds to be satisfied, while the Shapley value does not seem to be adjustable. On the contrary, comparative information inequalities prove to be not necessarily satisfied by all probabilities in the core and we must introduce the constrained core in order for these inequalities be satisfied. However, both the nucleolus and the Shapley value satisfy the comparative information inequalities, and the Shapley value does it more strictly than the nucleolus. (shrink)

The concern of this book is to see whether the phenomenological effervescence of politics is still possible to retrace the nucleolus of the political in its archetypical form.

The model of incomplete cooperative games incorporates uncertainty into the classical model of cooperative games by considering a partial characteristic function. Thus the values for some of the coalitions are not known. The main focus of this paper is 1-convexity under this framework. We are interested in two heavily intertwined questions. First, given an incomplete game, how can we fill in the missing values to obtain a complete 1-convex game? Second, how to determine in a rational, fair, and efficient way (...) the payoffs of players based only on the known values of coalitions? We illustrate the analysis with two classes of incomplete games—minimal incomplete games and incomplete games with defined upper vector. To answer the first question, for both classes, we provide a description of the set of 1-convex extensions in terms of its extreme points and extreme rays. Based on the description of the set of 1-convex extensions, we introduce generalisations of three solution concepts for complete games, namely the τ\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\tau $$\end{document}-value, the Shapley value and the nucleolus. For minimal incomplete games, we show that all of the generalised values coincide. We call it the average value and provide different axiomatisations. For incomplete games with defined upper vector, we show that the generalised values do not coincide in general. This highlights the importance and also the difficulty of considering more general classes of incomplete games. (shrink)

The discovery of the signal peptides that direct proteins to localize at the nucleolus is described here. The nucleolar targeting signal termed the NOS consists of clustered basic amino acids organized such that a portion also functions as the nuclear transporting signal. Although a NOS has been identified within the regulatory genes of human retroviruses, HTLV‐I and HIV‐I, signals of similar function in cellular proteins – such as heat shock proteins – may be induced through the configurational change of (...) protein structure by heat or stress. (shrink)

Ribosome biogenesis includes the making and processing of ribosomal RNAs, the biosynthesis of ribosomal proteins from their mRNAs in the cytosol and their transport to the nucleolus to assemble pre‐ribosomal particles. Several stresses including cellular senescence reduce nucleolar rRNA synthesis and maturation increasing the availability of ribosome‐free ribosomal proteins. Several ribosomal proteins can activate the p53 tumor suppressor pathway but cells without p53 can still arrest their proliferation in response to an imbalance between ribosomal proteins and mature rRNA production. (...) Recent results on senescence‐associated ribogenesis defects (SARD) show that the ribosomal protein S14 (RPS14 or uS11) can act as a CDK4/6 inhibitor linking ribosome biogenesis defects to the main engine of cell cycle progression. This work offers new insights into the regulation of the cell cycle and suggests novel avenues to design anticancer drugs. (shrink)

The formation of mature large rRNAs from larger primary transcripts is very different in bacterial and mammalian cells. In both, cotranscription can help to assure the coordinated production of various rRNA species. However, in bacteria, processing is ordered, initiated by cleavages at double‐stranded stems which enclose the mature sequences; several cleavages are required to produce each mature terminus; and the final steps occur in polysomes, apparently linked to continued protein synthesis. In mouse cells, in contrast, cleavages generate nearly all mature (...) termini stochastically and directly, with no evidence for double‐stranded stems as cleavage signals; and processing occurs in the nucleolus, long before any new rRNA chains arrive in polysomes. Spacer sequences also serve different potnetial functions at the evolutionary extremes. In bacteria, transcribed spacer sequences are associated with different secondary structures in the pre‐rRNA compared to the mature rRNA, and these may promote ribosome formation. In mammalian cells, analyses are too premature to assign any comparable function to transcribed spacer sequences, but the non‐transcribed spacers are probably critical in the organization and replication of nucleoli, functions that are absent from bacteria. (shrink)

In this paper, we study solution concepts for cooperative games with stochastic payoffs. we define four kinds of solution concepts, namely the most coalitional (marginal) stable solution and the fairest coalitional (marginal) solution, by minimizing the total variance of excesses of coalitions (individual players). All these four concepts are optimal solutions of corresponding optimal problem under the least square criterion. It turns out that the fairest coalitional (marginal) solution belongs to the set of the most coalitional (marginal) stable solutions. Inspired (...) by the definition of nucleolus, we propose various extended nucleolus based on lexicographic criterion. Furthermore, axiomatizations of the proposed solutions are exhibited through the linkage between the stochastic and deterministic models. (shrink)

Jazz band is a 3 player superadditive game in characteristic function form. Three players have to divide the payoff they can get, while being in a grand coalition, provided their individual and duo coalitions payoffs are known. Assumptions of individual and collective rationality lead to the notion of the core of the game. We discuss offers that cannot readily be refused [OCRR] as the solutions of the game in case of an empty core, when duo coalitions are the best options (...) but only for two out of three players. The experiment shows that even in case of an empty core the most probable results are three-way coalitions and the share of the weakest player usually exceeds his OCRR. The Shapley value is introduced and its fairness is discussed as it lies at the side of the core while, on the other hand, the nucleolus lies exactly at the center of the core. We conclude that, in spite of that, the Shapley value is the best candidate for a fair sharing solution of the jazz band game and other similar games as, opposite to the other values, it is dependent both on individual and duo coalitions payoffs. (shrink)

The main purpose of this article is to introduce the weighted ENSC value for cooperative transferable utility games which takes into account players’ selfishness about the payoff allocations. Similar to Shapley’s idea of a one-by-one formation of the grand coalition [Shapley ], we first provide a procedural implementation of the weighted ENSC value depending on players’ selfishness as well as their marginal contributions to the grand coalition. Second, in the spirit of the nucleolus [Schmeidler ], we prove that the (...) weighted ENSC value is obtained by lexicographically minimizing a complaint vector associated with a new complaint criterion relying on players’ selfishness. (shrink)

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

Eukaryotic genome DNA is wrapped around core histones and forms a nucleosome structure. Together with associated proteins and RNAs, these nucleosomes are organized three‐dimensionally in the cell as chromatin. Emerging evidence demonstrates that chromatin consists of rather irregular and variable nucleosome arrangements without the regular fiber structure and that its dynamic behavior plays a critical role in regulating various genome functions. Single‐nucleosome imaging is a promising method to investigate chromatin behavior in living cells. It reveals local chromatin motion, which reflects (...) chromatin organization not observed in chemically fixed cells. The motion data is like a gold mine. Data analyses from many aspects bring us more and more information that contributes to better understanding of genome functions. In this review article, we describe imaging of single‐nucleosomes and their tracked behavior through oblique illumination microscopy. We also discuss applications of this technique, especially in elucidating nucleolar organization in living cells. (shrink)