Search Results (212)

The technical complexity of organizing energy systems’ operation has recently been compounded by the complexity of reconciling the interests of individual entities involved in interactions. This study proposes a possible solution to the problem of modeling their relationships within a large system. Our solution takes into account multiple levels of interactions, imperfect information, and conflicting interests. We present a mathematical statement of the problem of optimal interactions between the centralized system and prosumers in the integrated energy system (IES) with due consideration of the layered architecture of the IES. The paper also contributes a model for arranging the interactions between centralized and distributed energy sources for cases when IES prosumers form coalitions. The implementation of this model is based on multi-agent techniques and cooperative game theory tools. In order to arrive at a rational arrangement of the interactions of prosumers in the IES, the model implements different approaches to the allocation of the coalition’s total payoff (the Shapley value, Modiclus, PreNucleolus solution concepts). Furthermore, we propose a criterion for deciding on the “best” imputation. We contribute a multi-agent system that implements the proposed model and use a test IES setup to validate the model by simulations. The results of the simulations ensure optimal interactions between the entities involved in the energy supply process within the IES and driven by their own interests. The results also elucidate the conditions that make it feasible for prosumers to form coalitions. Full article

CRM1 (XPO1) has been well-characterized as a shuttling receptor that mediates the export of protein and RNA cargos to the cytoplasm, and previous analyses have pinpointed several key residues (A541, F572, K568, S1055, and Q742) that modulate CRM1 export activity. CRM1 also has a less studied nuclear function in RNA biogenesis, which is reflected by its localization to the Cajal body and the nucleolus. Here, we have investigated how the mutation of these key residues affects the intranuclear localization of CRM1 and its ability to mediate export of endogenous cargos. We identify A541K as a separation-of-function mutant that reveals the independent nature of the Cajal body and nucleolar localizations of CRM1. We also show that the F572A mutation may have strikingly opposite effects on the export of specific cargos. Importantly, and in contrast to previous claims, our findings indicate that S1055 phosphorylation is not generally required for CRM1 function and that the Q742 is not a function-defining residue in human CRM1. Collectively, our findings provide new insights into an understudied aspect of CRM1 biology and highlight several important issues related to CRM1 function and regulation that need to be re-evaluated and addressed in more detail. Full article

Background/Objectives: Actin plays a crucial role not only in the cytoplasm, but also in the nucleus, influencing various cellular behaviors, including cell migration and gene expression. Recent studies reveal that nuclear actin dynamics is altered by cellular stresses, such as DNA damage; however, the effect of heat shock on nuclear actin dynamics, particularly in the nucleolus, remains unclear. This study aims to elucidate the contribution of nucleolar actin to cellular responses under heat shock conditions. Methods: Nuclear actin dynamics in response to heat shock were investigated using nAC-GFP, a GFP-tagged actin chromobody, to visualize nuclear actin in HeLa cells. Bioinformatic analyses were also performed. Results: Heat shock induced the reversible assembly of nAC-GFP in the nucleolus, with disassembly occurring upon recovery in a heat shock protein (Hsp) 70-dependent manner. Because the nucleolus, formed via liquid–liquid phase separation (LLPS), sequesters misfolded proteins under heat shock to prevent irreversible aggregation, we hypothesized that nucleolar actin-binding proteins might also be sequestered in a similar manner. Using several databases, we identified 47 actin-binding proteins localized in the nucleolus and determined the proportion of intrinsically disordered regions (IDRs) known to promote LLPS. Our analysis revealed that many of these 47 proteins exhibited high levels of IDRs. Conclusions: The findings from our bioinformatics analysis and further cellular studies may help elucidate new roles for actin in the heat shock response. Full article

Mast cell tumors (MCTs) are common skin neoplasms in dogs. Prognostic indicators include histologic grade, clinical stage, high Ki-67 index, elevated argyrophilic nucleolus organizer regions (AgNOR) index, c-kit mutations, and recurrence after surgery. Blood serum redox status has been shown to correlate with prognostic factors in canine lymphoma and mammary tumors. This study aimed to assess the correlation between established prognostic factors and serum redox status and lipid metabolism analytes in dogs with MCTs. Dogs with cutaneous (n = 33) or subcutaneous (n = 6) MCTs, without comorbidities, were studied. Staging was evaluated based on cytology of regional lymph nodes and ultrasound-guided liver and spleen aspiration cytology. Histologic grading and immunohistochemical staining for Ki-67 and KIT patterns were performed on excised tumor specimens. Dogs were categorized by Patnaik grading (1–3), Kiupel grading (low/high), metastatic status, Ki-67 positive nuclei per cm² (>23 or ≤23), and KIT pattern (I, II–III). Paraoxonase-1, Butyrylcholinesterase, Cupric Reducing Antioxidant Capacity (CUPRAC), Diacron Reactive Oxygen Metabolites (d-ROMs), and oxy-adsorbent levels were measured before any therapeutic intervention. ANOVA and independent t-tests were used to detect differences in the mean values among groups. Paraoxonase-1 activity was significantly lower in Patnaik grade 3 (p = 0.003) and Kiupel high-grade (p = 0.022) MCTs. No significant differences were found in CUPRAC, d-ROMs, or oxy-adsorbent levels across different prognostic groups. This study found a significant correlation between histologic grading and Paraoxonase-1 activity, suggesting a potential role of Paraoxonase-1 as a prognostic biomarker in canine MCTs. Full article

The cell cycle, essential for growth, reproduction, and genetic stability, is regulated by a complex network of cyclins, Cyclin-Dependent Kinases (CDKs), phosphatases, and checkpoints that ensure accurate cell division. CDKs and phosphatases are crucial for controlling cell cycle progression, with CDKs promoting it and phosphatases counteracting their activity to maintain balance. The nucleolus, as a biomolecular condensate, plays a key regulatory role by serving as a hub for ribosome biogenesis and the sequestration and release of various cell cycle regulators. This phase separation characteristic of the nucleolus is vital for the specific and timely release of Cdc14, required for most essential functions of phosphatase in the cell cycle. While mitosis distributes chromosomes to daughter cells, meiosis is a specialized division process that produces gametes and introduces genetic diversity. Central to meiosis is meiotic recombination, which enhances genetic diversity by generating crossover and non-crossover products. This process begins with the introduction of double-strand breaks, which are then processed by numerous repair enzymes. Meiotic recombination and progression are regulated by proteins and feedback mechanisms. CDKs and polo-like kinase Cdc5 drive recombination through positive feedback, while phosphatases like Cdc14 are crucial for activating Yen1, a Holliday junction resolvase involved in repairing unresolved recombination intermediates in both mitosis and meiosis. Cdc14 is released from the nucleolus in a regulated manner, especially during the transition between meiosis I and II, where it helps inactivate CDK activity and promote proper chromosome segregation. This review integrates current knowledge, providing a synthesis of these interconnected processes and an overview of the mechanisms governing cell cycle regulation and meiotic recombination. Full article

Background/objectives: Nucleolin is a major component of the nucleolus and is involved in various aspects of ribosome biogenesis. However, it is also implicated in non-nucleolar functions such as cell cycle regulation and proliferation, linking it to various pathologic processes. The aim of this study was to use differential gene expression analysis and Weighted Gene Co-expression Network analysis (WGCNA) to identify nucleolin-related regulatory pathways and possible key genes as novel therapeutic targets for cancer, viral infections and other diseases. Methods: We used two different siRNAs to downregulate the expression of nucleolin in a human hepatoblastoma (HepG2) cell line. We carried out RNA-sequencing (RNA-Seq), performed enrichment analysis of the pathways of the differentially expressed genes (DEGs) and identified protein–protein interaction (PPI) networks. Results: Both siRNAs showed high knockdown efficiency in HepG2 cells, resulting in the disruption of the nucleolar architecture and the downregulation of rRNA gene expression, both downstream hallmarks of a loss of nucleolin function. RNA-Seq identified 44 robust DEGs in both siRNA cell models. The enrichment analysis of the pathways of the downregulated genes confirmed the essential role of nucleolin in DNA replication and cell cycle processes. In addition, we identified seven hub genes linked to NCL: MCM6, MCM3, FEN1, MYBL2, MSH6, CDC6 and RBM14; all are known to be implicated in DNA replication, cell cycle progression and oncogenesis. Conclusions: Our findings demonstrate the functional consequences of nucleolin depletion in HepG2 and confirm the importance of nucleolin in DNA replication and cell cycle processes. These data will further enhance our understanding of the molecular and pathologic mechanisms of nucleolin and provide new therapeutic perspectives in disease. Full article

The purpose of this paper is to analyze the profitability of wind energy and demand response (DR) resources participating in the energy and frequency regulation markets. Since wind power producers (WPPs) must reduce their output to provide up-regulation and DR aggregators (DRAs) have to purchase additional power to facilitate down-regulation, this may result in revenue loss. If WPPs coordinate with DRAs, these two costs could be reduced. Thus, it would be profitable for WPPs and DRAs to form a coalition to participate in the regulation market. To better utilize the frequency response characteristics of wind and DR resources, this paper proposes a cooperation scheme to optimize the bidding strategy of the coalition. Furthermore, cooperative game theory methods, including Nucleolus- and Shapley-value-based models, are employed to fairly allocate additional benefits among WPPs and DRAs. The uncertainties associated with wind power and the behavior of DR customers are modeled through stochastic programming. In the optimization process, the decision-maker’s attitude toward risks is considered using conditional value at risk (CVaR). Case studies demonstrate that the proposed bidding strategy can improve the performance of the coalition and lead to higher benefits for both WPPs and DRAs. Specifically, the expected revenue of the coordinated strategies increased by 12.1% compared to that of uncoordinated strategies. Full article

Dendrolimus kikuchii Matsumura (D. kikuchii) is a serious pest of coniferous trees. Bacillus thuringiensis (Bt) has been widely studied and applied as a biological control agent for a variety of pests. Here, we found that the mortality rate of D. kikuchii larvae after being fed Bt reached 95.33% at 24 h; the midgut membrane tissue was ulcerated and liquefied, the MDA content in the midgut tissue decreased and the SOD, CAT and GPx enzyme activities increased, indicating that Bt has toxic effects on D. kikuchii larvae. In addition, transmission electron microscopy showed that Bt infection caused severe deformation of the nucleus of the midgut tissue of D. kikuchii larvae, vacuoles in the nucleolus, swelling and shedding of microvilli, severe degradation of mitochondria and endoplasmic reticulum and decreased number. Surprisingly, metabolomics and transcriptome association analysis revealed that four metabolic-related signaling pathways, Nicotinate and nicotinamide metabolism, Longevity regulating pathway—worm, Vitamin digestion and absorption and Lysine degradation, were co-annotated in larvae. More surprisingly, Niacinamide was a common differential metabolite in the first three signaling pathways, and both Niacinamide and L-2-Aminoadipic acid were reduced. The differentially expressed genes involved in the four signaling pathways, including NNT, ALDH, PNLIP, SETMAR, GST and RNASEK, were significantly down-regulated, but only SLC23A1 gene expression was up-regulated. Our results illustrate the effects of Bt on the 5th instar larvae of D. kikuchii at the tissue, cell and molecular levels, and provide theoretical support for the study of Bt as a new biological control agent for D. kikuchii. Full article

The main role of the nucleolus is ribosomal biogenesis, but it also responds to stress with changes in number, area, and/or morphology. Nucleoli with transcriptionally active ribosomal RNA genes are selectively stained by silver nitrate. Hypothesising that fire recurrence and/or polyethylene glycol (PEG)-induced water stress would cause nucleolar changes in Pinus pinaster roots, nucleolar parameters were analysed upon the germination of seeds harvested in post-fire naturally regenerated stands with different fire regimes. An unburned stand was used as a control. The nucleoli number varied from 1 to 15 among stands and PEG treatments, but a mode of five or six nucleoli was found. The number of nucleoli per interphase (N) increased (p < 0.001) with fire recurrence (stand effect). Increasing PEG concentration (treatment effect) decreased the nucleoli number, notably in the stand with the highest fire recurrence. The nucleolar area decreased (p < 0.001) with increased nucleoli number, fire recurrence, and/or PEG concentration. Fire recurrence and water scarcity are forecasted for future climate scenarios. As demonstrated earlier, these factors could influence protein synthesis or the cell cycle’s regularity, which are crucial processes for root growth and pine seedling establishment. Furthermore, this work revealed that nucleolar parameters could be suitable biomarkers for pine stress studies. Full article

Neuropathic pain is a prevalent and debilitating chronic syndrome that is often resistant to treatment. It frequently arises as a consequence of damage to first-order nociceptive neurons in the lumbar dorsal root ganglia (DRG), with chromatolysis being the primary neuropathological response following sciatic nerve injury (SNI). Nevertheless, the function of miRNAs in modulating this chromatolytic response in the context of neuropathic pain remains unexplored. Our previous research demonstrated that the intracisternal administration of a miR-30c mimic accelerates the development of neuropathic pain, whereas the inhibition of miR-30c prevents pain onset and reverses established allodynia. In the present study, we sought to elucidate the role of miR-30c-5p in the pathogenesis of neuropathic pain, with a particular focus on its impact on DRG neurons following SNI. The organisation and ultrastructural changes in DRG neurons, particularly in the protein synthesis machinery, nucleolus, and Cajal bodies (CBs), were analysed. The results demonstrated that the administration of a miR-30c-5p mimic exacerbates chromatolytic damage and nucleolar stress and induces CB depletion in DRG neurons following SNI, whereas the administration of a miR-30c-5p inhibitor alleviates these effects. We proposed that three essential cellular responses—nucleolar stress, CB depletion, and chromatolysis—are the pathological mechanisms in stressed DRG neurons underlying neuropathic pain. Moreover, miR-30c-5p inhibition has a neuroprotective effect by reducing the stress response in DRG neurons, which supports its potential as a therapeutic target for neuropathic pain management. This study emphasises the importance of miR-30c-5p in neuropathic pain pathogenesis and supports further exploration of miRNA-based treatments. Full article

It became clear more than 20 years ago that the nucleolus not only performs the most important biological function of assembling ribonucleic particles but is also a key controller of many cellular processes, participating in cellular adaptation to stress. The nucleolus’s multifunctionality is due to the peculiarities of its biogenesis. The nucleolus is a multilayered biomolecular condensate formed by liquid–liquid phase separation (LLPS). In this review, we focus on changes occurring in the nucleolus during cellular stress, molecular features of the nucleolar response to abnormal and stressful conditions, and the role of long non-coding RNAs transcribed from the intergenic spacer region of ribosomal DNA (IGS rDNA). Full article

Oocyte meiotic maturation includes large-scale chromatin remodeling as well as cytoskeleton and nuclear envelope rearrangements. This review addresses the dynamics of key cytoskeletal proteins (tubulin, actin, vimentin, and cytokeratins) and nuclear envelope proteins (lamin A/C, lamin B, and the nucleoporin Nup160) in parallel with chromatin reorganization in maturing mouse oocytes. A major feature of this reorganization is the concentration of heterochromatin into a spherical perinucleolar rim called surrounded nucleolus or karyosphere. In early germinal vesicle (GV) oocytes with non-surrounded nucleolus (without karyosphere), lamins and Nup160 are at the nuclear envelope while cytoplasmic cytoskeletal proteins are outside the nucleus. At the beginning of karyosphere formation, lamins and Nup160 follow the heterochromatin relocation assembling a new spherical structure in the GV. In late GV oocytes with surrounded nucleolus (fully formed karyosphere), the nuclear envelope gradually loses its integrity and cytoplasmic cytoskeletal proteins enter the nucleus. At germinal vesicle breakdown, lamin B occupies the karyosphere interior while all the other proteins stay at the karyosphere border or connect to chromatin. In metaphase oocytes, lamin A/C surrounds the spindle, Nup160 localizes to its poles, actin and lamin B are attached to the spindle fibers, and cytoplasmic intermediate filaments associate with both the spindle fibers and the metaphase chromosomes. Full article

Energy Communities (ECs) are aggregations of users that cooperate to achieve economic benefits by sharing energy instead of operating individually in the so-called “disagreement” case. As there is no unique notion of fairness for the cost/profit allocation of ECs, this paper aims to identify an allocation method that allows for an appropriate weighting of both the interests of an EC as a whole and those of all its members. The novelty is in comparing different optimization approaches and cooperative allocation criteria, satisfying different notions of fairness, to assess which one may be best suited for an EC. Thus, a cooperative model is used to optimize the operation of an EC that includes two consumers and two solar PV prosumers. The model is solved by the “Social Welfare” approach to maximizing the total “incremental” economic benefit (i.e., cost saving and/or profit increase) and by the “Nash Bargaining” approach to simultaneously maximize the total and individual incremental economic benefits, with respect to the “disagreement” case. Since the “Social Welfare” approach could lead to an unbalanced benefit distribution, the Shapley value and Nucleolus criteria are applied to re-distribute the total incremental economic benefit, leading to higher annual cost savings for consumers with lower electricity demand. Compared to “Social Welfare” without re-distribution, the Nash Bargaining distributes 39–49% and 9–17% higher annual cost savings to consumers with lower demand and to prosumers promoting the energy sharing within the EC, respectively. However, total annual cost savings drop by a maximum of 5.5%, which is the “Price of Fairness”. Full article

Nuclear bodies are structures in eukaryotic cells that lack a plasma membrane and are considered protein condensates, DNA, or RNA molecules. Known nuclear bodies include the nucleolus, Cajal bodies, and promyelocytic leukemia nuclear bodies. These bodies are involved in the concentration, exclusion, sequestration, assembly, modification, and recycling of specific components involved in the regulation of ribosome biogenesis, RNA transcription, and RNA processing. Additionally, nuclear bodies have been shown to participate in cellular processes such as the regulation of transcription of the cell cycle, mitosis, apoptosis, and the cellular stress response. The dynamics and functions of these bodies depend on the state of the cell. It is now known that both DNA and RNA viruses can direct their proteins to nuclear bodies, causing alterations in their composition, dynamics, and functions. Although many of these mechanisms are still under investigation, it is well known that the interaction between viral and nuclear body proteins is necessary for the success of the viral infection cycle. In this review, we concisely describe the interaction between viral and nuclear body proteins. Furthermore, we focus on the role of the nucleolus in RNA virus infections. Finally, we discuss the possible implications of the interaction of viral proteins on cellular transcription and the formation/degradation of non-coding RNAs. Full article

Movement proteins (MPs) encoded by plant viruses are essential for cell-to-cell transport of viral genomes through plasmodesmata. The genome of hibiscus green spot virus contains a module of two MP genes termed ‘binary movement block’ (BMB), encoding the proteins BMB1 and BMB2. Here, BMB1 is shown to induce a defense response in Nicotiana benthamiana plants that inhibits BMB-dependent virus transport. This response is characterized by the accumulation of reactive oxygen species, callose deposition in the cell wall, and upregulation of 9-LOX expression. However, the BMB1-induced response is inhibited by coexpression with BMB2. Furthermore, BMB1 is found to localize to subnuclear structures, in particular to Cajal bodies, in addition to the cytoplasm. As shown in experiments with a BMB1 mutant, the localization of BMB1 to nuclear substructures enhances BMB-dependent virus transport. Thus, the virus transport mediated by BMB proteins is modulated by (i) a BMB1-induced defense response that inhibits transport, (ii) suppression of the BMB1-induced response by BMB2, and (iii) the nuclear localization of BMB1 that promotes virus transport. Collectively, the data presented demonstrate multiple levels of interactions between viral pathogens and their plant hosts during virus cell-to-cell transport. Full article