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Purpose: Matrin 3 (MATR3) is a nuclear matrix protein involved in mRNA stabilization, nuclear retention of hyper-edited RNAs, and RNA splicing. The role of MATR3 in cancer is still unclear. The present study aimed to investigate expression levels and prognostic significance of MATR3 in stage I and II non-small cell lung cancer (NSCLC) patients. Methods: We examined MATR3 protein immunohistochemically in tumoral and non-tumoral tissue sections from n = 67 NSCLC patients treated at hospital, and MATR3 mRNA from The Cancer Genome Atlas (TCGA) cohort with respect to valid prognostic and predictive features, as well as treatment outcome. Results: Significantly higher immunohistochemical levels of MATR3 protein were found in tumor-adjacent tissue compared to cancer (p = 0.049). A decrease in MATR3 protein expression was found to be a significant independent adverse prognostic factor for patients overall survival (p = 0.007). By contrast, we observed higher MATR3 mRNA levels in tumoral tissue compared to control lung tissues (p < 0.001). Based on the TCGA dataset, we reported that high MATR3 mRNA level was significantly associated with worse OS of NSCLC patients (p < 0.001); however, it was not an independent prognostic marker (p = 0.156). The discrepancies in prognostic significance of MATR3 gene mRNA and protein levels imply a need for further investigation. Conclusion: In conclusion, the present study warrants further investigation into the biological and prognostic value of MATR3 as a potential prognostic marker in early-stage NSCLC patients. [ABSTRACT FROM AUTHOR]

Muscle biopsy findings from anti-NXP-2 antibody-positive individuals show less active inflammation and more muscle atrophy when compared to patients with anti-NXP-2 antibody-negative DM ([[26]]). This work demonstrates how intestinal vasculopathy in a DM patient may present in adults and the differential that rheumatology providers should consider when approaching a DM patient with GI symptoms. Inflammatory myositis and systemic lupus erythematosus (SLE) mesenteric vasculitis overlap In a multicenter retrospective review of 1,718 adult and pediatric patients diagnosed as having SLE from 2010 to 2019 in an American academic medical center, 108 patients (6.3%) were also diagnosed as having inflammatory myositis ([7]). [Extracted from the article]

The regulation of gene expression is a critical process for establishing and maintaining cellular identity. Gene expression is controlled through a chromatin‐based mechanism in the nucleus of eukaryotic cells. Recent studies suggest that chromatin accessibility and the higher‐order structure of chromatin affect transcriptional outcome. This is especially evident when cells change their fate during development and nuclear reprogramming. Furthermore, non‐chromosomal contents of the cell nucleus, namely nucleoskeleton proteins, can also affect chromatin and nuclear structures, resulting in transcriptional alterations. Here, we review our current mechanistic understanding about how chromatin and nuclear structures impact transcription in the course of embryonic development, cellular differentiation and nuclear reprogramming, and also discuss unresolved questions that remain to be addressed in the field. [ABSTRACT FROM AUTHOR]

How cells adjust their growth to the spatial and mechanical constraints of their surrounding environment is central to many aspects of biology. Here, we examined how extracellular matrix (ECM) rigidity affects cell division. We found that cells divide more rapidly when cultured on rigid substrates. While we observed no effect of ECM rigidity on rounding or postmitotic spreading duration, we found that changes in matrix stiffness impact mitosis progression. We noticed that ECM elasticity up-regulates the expression of the linker of nucleoskeleton and cytoskeleton (LINC) complex component SUN2, which in turn promotes metaphase-to-anaphase transition by acting on mitotic spindle formation, whereas when cells adhere to soft ECM, low levels of SUN2 expression perturb astral microtubule organization and delay the onset of anaphase. [ABSTRACT FROM AUTHOR]

The European starling, Sturnus vulgaris, is an ecologically significant, globally invasive avian species that is also suffering from a major decline in its native range. Here, we present the genome assembly and long‐read transcriptome of an Australian‐sourced European starling (S. vulgaris vAU), and a second, North American, short‐read genome assembly (S. vulgaris vNA), as complementary reference genomes for population genetic and evolutionary characterization. S. vulgaris vAU combined 10× genomics linked‐reads, low‐coverage Nanopore sequencing, and PacBio Iso‐Seq full‐length transcript scaffolding to generate a 1050 Mb assembly on 6222 scaffolds (7.6 Mb scaffold N50, 94.6% busco completeness). Further scaffolding against the high‐quality zebra finch (Taeniopygia guttata) genome assigned 98.6% of the assembly to 32 putative nuclear chromosome scaffolds. Species‐specific transcript mapping and gene annotation revealed good gene‐level assembly and high functional completeness. Using S. vulgaris vAU, we demonstrate how the multifunctional use of PacBio Iso‐Seq transcript data and complementary homology‐based annotation of sequential assembly steps (assessed using a new tool, saaga) can be used to assess, inform, and validate assembly workflow decisions. We also highlight some counterintuitive behaviour in traditional busco metrics, and present buscomp, a complementary tool for assembly comparison designed to be robust to differences in assembly size and base‐calling quality. This work expands our knowledge of avian genomes and the available toolkit for assessing and improving genome quality. The new genomic resources presented will facilitate further global genomic and transcriptomic analysis on this ecologically important species. [ABSTRACT FROM AUTHOR]

The CUPID-Mo experiment to search for 0 ν β β decay in 100 Mo has been recently completed after about 1.5 years of operation at Laboratoire Souterrain de Modane (France). It served as a demonstrator for CUPID, a next generation 0 ν β β decay experiment. CUPID-Mo was comprised of 20 enriched Li 2 100 MoO 4 scintillating calorimeters, each with a mass of ∼ 0.2 kg, operated at ∼ 20 mK. We present here the final analysis with the full exposure of CUPID-Mo ( 100 Mo exposure of 1.47 kg × year ) used to search for lepton number violation via 0 ν β β decay. We report on various analysis improvements since the previous result on a subset of data, reprocessing all data with these new techniques. We observe zero events in the region of interest and set a new limit on the 100 Mo 0 ν β β decay half-life of T 1 / 2 0 ν > 1.8 × 10 24 year (stat. + syst.) at 90% CI. Under the light Majorana neutrino exchange mechanism this corresponds to an effective Majorana neutrino mass of m β β < (0.28 - 0.49) eV, dependent upon the nuclear matrix element utilized. [ABSTRACT FROM AUTHOR]

Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation. PML NBs recruit many partner proteins, but the actual biochemical mechanism underlying their pleiotropic functions remains elusive. Similarly, PML role in embryonic stem cell (ESC) and retro-element biology is unsettled. Here we demonstrate that PML is essential for oxidative stress-driven partner SUMO2/3 conjugation in mouse ESCs (mESCs) or leukemia, a process often followed by their poly-ubiquitination and degradation. Functionally, PML is required for stress responses in mESCs. Differential proteomics unravel the KAP1 complex as a PML NB-dependent SUMO2-target in arsenic-treated APL mice or mESCs. PML-driven KAP1 sumoylation enables activation of this key epigenetic repressor implicated in retro-element silencing. Accordingly, Pml−/− mESCs re-express transposable elements and display 2-Cell-Like features, the latter enforced by PML-controlled SUMO2-conjugation of DPPA2. Thus, PML orchestrates mESC state by coordinating SUMO2-conjugation of different transcriptional regulators, raising new hypotheses about PML roles in cancer. Here the authors identify novel PML-partners and demonstrate that PML NBs control their sumoylation and that PML-controlled sumoylation of transcriptional regulators maintains the embryonic stem cell transcriptome and transposable element silencing. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recombinant human interferon α-2b is a cytokine with antiviral, antiproliferative, antitumor, and immunomodulatory activities, which has certain preventive and curative effects on scar tissue. OBJECTIVE: To explore the effects of recombinant human interferon α-2b on scar fibroblasts and to observe its effects on the proliferation and migration abilities of scar fibroblasts. METHODS: In vitro scar fibroblasts were cultured to logarithmic growth phase and treated with 0, 5 000, 10 000, 20 000 IU/mL recombinant human interferon α-2b for 48 hours. Cell proliferation was observed by EdU staining and cell migration was detected through cell scratch test and Transwell test. Expression levels of proliferating cell nuclear antigen and matrix metalloproteinase 2, proliferation- and migration-associated proteins of scar fibroblasts were detected by western blot assay. RESULTS AND CONCLUSION: The results of in vitro cell experiments showed that, compared with the control group, recombinant human interferon α-2b could significantly decrease the number of EdU-positive cells, the wound healing rate, the number of migrated cells, and the protein levels of proliferating cell nuclear antigen and matrix metalloproteinase 2 (P < 0.05). All these findings indicate that recombinant human interferon α-2b can inhibit the proliferation and migration of scar fibroblasts. [ABSTRACT FROM AUTHOR]

Summary: The plant nucleus provides a major hub for environmental signal integration at the chromatin level. Multiple light signaling pathways operate and exchange information by regulating a large repertoire of gene targets that shape plant responses to a changing environment. In addition to the established role of transcription factors in triggering photoregulated changes in gene expression, there are eminent reports on the significance of chromatin regulators and nuclear scaffold dynamics in promoting light‐induced plant responses. Here, we report and discuss recent advances in chromatin‐regulatory mechanisms modulating plant architecture and development in response to light, including the molecular and physiological roles of key modifications such as DNA, RNA and histone methylation, and/or acetylation. The significance of the formation of biomolecular condensates of key light signaling components is discussed and potential applications to agricultural practices overviewed. [ABSTRACT FROM AUTHOR]

Simultaneously enlarging perovskite grain size and passivating grain boundary defects are highly desired for achieving a high photovoltaic performance of perovskite solar cells (PSCs). Herein, the amino‐functionalized carbon nanotube (NH2‐CNT) is introduced into the perovskite precursor solution as both the crystal growth templates and the grain boundary passivator to modulate the grain growth and carrier behavior dynamics of perovskite films. The amino groups can anchor the perovskite crystal nuclear on the NH2‐CNT skeleton to obtain perovskite films with larger grain sizes. Moreover, the NH2‐CNT mainly located at the grain boundaries can not only effectively passivates the defects due to the strong interaction between amino group and perovskite, but also tunes the energy band alignment and provides a faster carrier transport channel to accelerate the electrons extraction and transfer process. As a result, the MAPbI3‐based PSCs with NH2‐CNT exhibit a power conversion efficiency of 21.01%. This work presents a promising strategy for fabricating efficient and stable PSCs by tuning perovskite films using environmentally friendly functionalized carbon materials. [ABSTRACT FROM AUTHOR]

Abstract Background Chromatin architecture is critical for gene expression during development. Matrix attachment regions (MARs) control and regulate chromatin dynamics. The position of MARs in the genome determines the expression of genes in the organism. In this study, we set out to elucidate how MARs temporally regulate the expression of the fibroin heavy chain (FIBH) gene during development. We addressed this by identifying MARs and studying their distribution and differentiation, in the posterior silk glands of Bombyx mori during 5th instar development. Results Of the MARs identified on three different days, 7.15% MARs were common to all 3 days, whereas, 1.41, 19.27 and 52.47% MARs were unique to day 1, day 5, and day 7, respectively highlighting the dynamic nature of the matrix associated DNA. The average chromatin loop length based on the chromosome wise distribution of MARs and the distances between these MAR regions decreased from day 1 (253.91 kb) to day 5 (73.54 kb) to day 7 (39.19 kb). Further significant changes in the MARs in the vicinity of the FIBH gene were found during different days of 5th instar development which implied their role in the regulation and expression of the FIBH gene. Conclusions The presence of MARs in the flanking regions of genes found to exhibit differential expression during 5th instar development indicates their possible role in the regulation of their expression. This reiterates the importance of MARs in the genomic functioning as regulators of the molecular mechanisms in the nucleus. This is the first study that takes into account the tissue specific genome-wide MAR association and the potential role of these MARs in developmentally regulated gene expression. The current study lays a foundation to understand the genome wide regulation of chromatin during development.

Abstract Objectives The nuclear matrix maintains and regulates chromatin structure. RNA is an integral component of the nuclear matrix and is essential to its structural maintenance. Bombyx mori is a major economic contributor in the sericulture industry and produces fibroin—the most important silk protein in its posterior silk glands during 5th instar larval stage. The present study investigates the composition of nuclear matrix RNA prepared from the posterior silk glands of Bombyx mori during fifth instar larval stage where maximum silk production occurs. The datasets from which the analysis is carried out are part of data note titled “Nuclear matrix associated RNA datasets of posterior silk glands of Bombyx mori during 5th instar larval development”. Results The results showed significant enrichment of nuclear matrix RNA from day 1, to day 5 and day 7. Nuclear RNA showed increased abundance from day 1 to day 5 and day 7. Nuclear matrix RNA exhibited repetitive RNA sequences, of which UGUCC and GCUGGU were the most abundant. Genes involved in metabolic pathways showed significant enrichment correlating with silk production. These results emphasize the role of dynamic, repetitive DNA transcripts in chromatin architecture and further reveal the close association between the nuclear matrix and gene expression.

[Display omitted] • hnRNP U is a nuclear scaffolding protein that bridges DNA, RNA and protein. • While hnRNP U is known to bind RNA, its binding specificity remains unclear. • Binding analysis reveals that hnRNP U binds RNA promiscuously. • Binding selectivity of hnRNP U's RGG/RG motifs is ablated by surrounding sequence. • RGG/RG motifs serve to augment affinity of neighboring specific RNA binding domains. The abundant nuclear protein hnRNP U interacts with a broad array of RNAs along with DNA and protein to regulate nuclear chromatin architecture. The RNA-binding activity is achieved via a disordered ∼100 residue C-terminal RNA-binding domain (RBD) containing two distinct RGG/RG motifs. Although the RNA-binding capabilities of RGG/RG motifs have been widely reported, less is known about hnRNP U's RNA-binding selectivity. Furthermore, while it is well established that hnRNP U binds numerous nuclear RNAs, it remains unknown whether it selectively recognizes sequence or structural motifs in target RNAs. To address this question, we performed equilibrium binding assays using fluorescence anisotropy (FA) and electrophoretic mobility shift assays (EMSAs) to quantitatively assess the ability of human hnRNP U RBD to interact with segments of cellular RNAs identified from eCLIP data. These RNAs often, but not exclusively, contain poly-uridine or 5′-AGGGAG sequence motifs. Detailed binding analysis of several target RNAs reveal that the hnRNP U RBD binds RNA in a promiscuous manner with high affinity for a broad range of structured RNAs, but with little preference for any distinct sequence motif. In contrast, the isolated RGG/RG of hnRNP U motif exhibits a strong preference for G-quadruplexes, similar to that observed for other RGG motif bearing peptides. These data reveal that the hnRNP U RBD attenuates the RNA binding selectivity of its core RGG motifs to achieve an extensive RNA interactome. We propose that a critical role of RGG/RG motifs in RNA biology is to alter binding affinity or selectivity of adjacent RNA-binding domains. [ABSTRACT FROM AUTHOR]

Nuclear matrix elements (NMEs) for neutrinoless double-beta (0 ν β β) decay in candidate nuclei play a crucial role in interpreting results from current experiments and in designing future ones. Accurate NME values serve as important nuclear inputs for constraining parameters in new physics, such as neutrino mass and the Wilson coefficients of lepton-number-violating (LNV) operators. In this study, we present a comprehensive calculation of NMEs for 0 ν β β decay in 76Ge, 82Se, 100Mo, 130Te, and 136Xe, using nuclear wave functions obtained from multi-reference covariant density functional theory (MR-CDFT). We employ three types of transition potentials at the leading order in chiral effective field theory. Our results, along with recent data, are utilized to constrain the coefficients of LNV operators. The results demonstrate that the combined NMEs based on the Feynman diagrams at the hadronic scale for the nonstandard mechanisms leads to the uncertainty by different nuclear models comparable to that for the standard mechanism. The use of NMEs from various nuclear models does not dramatically change the parameter space intervals for the coefficients, although MR-CDFT yields the most stringent constraint. Furthermore, our NMEs can also be used to perform a more comprehensive analysis with multiple isotopes. [ABSTRACT FROM AUTHOR]

Starting from a manifestly Lorentz-invariant chiral Lagrangian, we present a model-free prediction for the transition amplitude of the process n n → p p e − e − induced by light Majorana neutrinos, which is a key process of the neutrinoless double beta decay (0 ν β β) in heavy nuclei employed in large-scale searches. Contrary to the nonrelativistic case, we show that the transition amplitude can be renormalized at leading order without any uncertain contact operators. The predicted amplitude defines a stringent benchmark for the previous estimation with model-dependent inputs, and greatly reduces the uncertainty of 0 ν β β transition operator in the calculations of nuclear matrix elements. Generalizations of the present framework could also help to address the uncertainties in 0 ν β β decay induced by other mechanisms. In addition, the present work motivates a relativistic ab initio calculation of 0 ν β β decay in light and medium-mass nuclei. [ABSTRACT FROM AUTHOR]

The neutrinoless double- β (0 ν β β) decay and the double Gamow-Teller (DGT) transition are investigated with the state-of-the-art Relativistic Configuration-interaction Density functional theory. A strong linear correlation between the nuclear matrix elements (NMEs) of the 0 ν β β decay and the DGT transition is demonstrated. This linear correlation is found to originate from the similarity of the leading-order term of the 0 ν β β -decay operator and the DGT-transition one, as revealed by expanding the 0 ν β β -decay operator in terms of the spherical harmonics. The present results provide a strong support to constrain the 0 ν β β -decay NMEs through the double charge-exchange reactions. [ABSTRACT FROM AUTHOR]

• Patients with multiple endocrine neoplasia type 1 (MEN1) may face an increased risk for breast carcinogenesis. • Menin is predominantly a nuclear scaffold protein to interact with various signaling regulators in breast carcinogenesis. • Four menin-targeted small molecules were tested in breast cancer. • Attesting to anti-cancer effects of other menin inhibitors in breast carcinoma are in an urgent needed. To date, mounting evidence have shown that patients with multiple endocrine neoplasia type 1 (MEN1) may face an increased risk for breast carcinogenesis. The product of the MEN 1 gene, menin, was also indicated to be an important regulator in breast cancer signaling network. Menin directly interacts with MLL, EZH2, JunD, NF-κB, PPARγ, VDR, Smad3, β-catenin and ERα to modulate gene transcriptions leading to cell proliferation inhibition. Moreover, interaction of menin-FANCD2 contributes to the enhancement of BRCA1-mediated DNA repair mechanism. Ectopic expression of menin causes Bax-, Bak- and Caspase-8-dependent apoptosis. However, despite numbers of menin inhibitors were exploited in other cancers, data on the usage of menin inhibitors in breast cancer treatment remain limited. In this review, we focused on the menin associated signaling pathways and gene transcription regulations, with the aim of elucidating its molecular mechanisms and of guiding the development of novel menin targeted drugs in breast cancer therapy. [ABSTRACT FROM AUTHOR]

Introduction: Juvenile dermatomyositis (JDM) is characterized by persistent non-purulent inflammation in the muscle and skin. The underlying mechanisms still remain uncertain. This study aims to elucidate the mechanism of interleukin-6 (IL-6) activation of Janus kinase/signal transducer and activator of transcription 3 pathway (JAK/STAT3), contributing to the pathogenesis of JDM.Serum IL-6 levels were compared between 72 newly diagnosed patients with JDM and the same patient cohort in treatment remission. Single-cell RNA sequencing (scRNA-seq) was employed to identify differential signaling pathway expression in muscle biopsy samples from two patients with JDM and healthy controls. Immunohistochemistry was used to examine differences in STAT3 phosphorylation between JDM and control muscle tissues. In vitro, skeletal muscle cell lines were stimulated with IL-6, and the transcription levels of genes related to mitochondrial calcium channels were quantified via reverse transcription-polymerase chain reaction (RT-PCR). Reactive oxygen species (ROS) production was measured in both IL-6 treated and untreated groups. ROS levels were then compared between IL-6 receptor antagonist pre-treated skeletal muscle cells and untreated cells.IL-6 levels in newly onset patients with JDM were significantly higher compared to the same patient cohort in remission states (p < 0.0001). Serum IL-6 was significantly increased in patients with negative myositis specific antibody (MSA), positive melanoma differentiation associated protein 5 (MDA5) and positive nuclear matrix protein 2 (NXP2), yet not for JDM with positive transcriptional intermediary factor γ (TIF1γ), based on subgroup analysis. ScRNA-seq analysis of muscle biopsies from patients with MDA5-positive JDM and patients with MSA negative JDM revealed abnormal activation of the JAK/STAT3 pathway in skeletal myocytes, macrophages, and vascular endothelial cells. The phosphorylation levels of STAT3 were elevated in active JDM cases. Transcription of the calcium channel modulation gene sarcolipin (SLN) was significantly higher in JDM primary skeletal muscle cells compared to normal cells. In vitro, IL-6 enhanced SLN transcription and induced ROS production, and blocking the IL-6 receptor resulted in decreased ROS generation in skeletal muscle cells.IL-6/JAK/STAT3 signaling pathway was abnormally activated in patients with JDM. IL-6 may be involved in the pathogenesis of muscle damage by triggering the development of calcium overload and production of ROS. Blockade of the IL-6/JAK/STAT3 pathway can be a potential treatment option for JDM, especially MDA5-positive patients and those who are negative for MSA.Methods: Juvenile dermatomyositis (JDM) is characterized by persistent non-purulent inflammation in the muscle and skin. The underlying mechanisms still remain uncertain. This study aims to elucidate the mechanism of interleukin-6 (IL-6) activation of Janus kinase/signal transducer and activator of transcription 3 pathway (JAK/STAT3), contributing to the pathogenesis of JDM.Serum IL-6 levels were compared between 72 newly diagnosed patients with JDM and the same patient cohort in treatment remission. Single-cell RNA sequencing (scRNA-seq) was employed to identify differential signaling pathway expression in muscle biopsy samples from two patients with JDM and healthy controls. Immunohistochemistry was used to examine differences in STAT3 phosphorylation between JDM and control muscle tissues. In vitro, skeletal muscle cell lines were stimulated with IL-6, and the transcription levels of genes related to mitochondrial calcium channels were quantified via reverse transcription-polymerase chain reaction (RT-PCR). Reactive oxygen species (ROS) production was measured in both IL-6 treated and untreated groups. ROS levels were then compared between IL-6 receptor antagonist pre-treated skeletal muscle cells and untreated cells.IL-6 levels in newly onset patients with JDM were significantly higher compared to the same patient cohort in remission states (p < 0.0001). Serum IL-6 was significantly increased in patients with negative myositis specific antibody (MSA), positive melanoma differentiation associated protein 5 (MDA5) and positive nuclear matrix protein 2 (NXP2), yet not for JDM with positive transcriptional intermediary factor γ (TIF1γ), based on subgroup analysis. ScRNA-seq analysis of muscle biopsies from patients with MDA5-positive JDM and patients with MSA negative JDM revealed abnormal activation of the JAK/STAT3 pathway in skeletal myocytes, macrophages, and vascular endothelial cells. The phosphorylation levels of STAT3 were elevated in active JDM cases. Transcription of the calcium channel modulation gene sarcolipin (SLN) was significantly higher in JDM primary skeletal muscle cells compared to normal cells. In vitro, IL-6 enhanced SLN transcription and induced ROS production, and blocking the IL-6 receptor resulted in decreased ROS generation in skeletal muscle cells.IL-6/JAK/STAT3 signaling pathway was abnormally activated in patients with JDM. IL-6 may be involved in the pathogenesis of muscle damage by triggering the development of calcium overload and production of ROS. Blockade of the IL-6/JAK/STAT3 pathway can be a potential treatment option for JDM, especially MDA5-positive patients and those who are negative for MSA.Results: Juvenile dermatomyositis (JDM) is characterized by persistent non-purulent inflammation in the muscle and skin. The underlying mechanisms still remain uncertain. This study aims to elucidate the mechanism of interleukin-6 (IL-6) activation of Janus kinase/signal transducer and activator of transcription 3 pathway (JAK/STAT3), contributing to the pathogenesis of JDM.Serum IL-6 levels were compared between 72 newly diagnosed patients with JDM and the same patient cohort in treatment remission. Single-cell RNA sequencing (scRNA-seq) was employed to identify differential signaling pathway expression in muscle biopsy samples from two patients with JDM and healthy controls. Immunohistochemistry was used to examine differences in STAT3 phosphorylation between JDM and control muscle tissues. In vitro, skeletal muscle cell lines were stimulated with IL-6, and the transcription levels of genes related to mitochondrial calcium channels were quantified via reverse transcription-polymerase chain reaction (RT-PCR). Reactive oxygen species (ROS) production was measured in both IL-6 treated and untreated groups. ROS levels were then compared between IL-6 receptor antagonist pre-treated skeletal muscle cells and untreated cells.IL-6 levels in newly onset patients with JDM were significantly higher compared to the same patient cohort in remission states (p < 0.0001). Serum IL-6 was significantly increased in patients with negative myositis specific antibody (MSA), positive melanoma differentiation associated protein 5 (MDA5) and positive nuclear matrix protein 2 (NXP2), yet not for JDM with positive transcriptional intermediary factor γ (TIF1γ), based on subgroup analysis. ScRNA-seq analysis of muscle biopsies from patients with MDA5-positive JDM and patients with MSA negative JDM revealed abnormal activation of the JAK/STAT3 pathway in skeletal myocytes, macrophages, and vascular endothelial cells. The phosphorylation levels of STAT3 were elevated in active JDM cases. Transcription of the calcium channel modulation gene sarcolipin (SLN) was significantly higher in JDM primary skeletal muscle cells compared to normal cells. In vitro, IL-6 enhanced SLN transcription and induced ROS production, and blocking the IL-6 receptor resulted in decreased ROS generation in skeletal muscle cells.IL-6/JAK/STAT3 signaling pathway was abnormally activated in patients with JDM. IL-6 may be involved in the pathogenesis of muscle damage by triggering the development of calcium overload and production of ROS. Blockade of the IL-6/JAK/STAT3 pathway can be a potential treatment option for JDM, especially MDA5-positive patients and those who are negative for MSA.Conclusions: Juvenile dermatomyositis (JDM) is characterized by persistent non-purulent inflammation in the muscle and skin. The underlying mechanisms still remain uncertain. This study aims to elucidate the mechanism of interleukin-6 (IL-6) activation of Janus kinase/signal transducer and activator of transcription 3 pathway (JAK/STAT3), contributing to the pathogenesis of JDM.Serum IL-6 levels were compared between 72 newly diagnosed patients with JDM and the same patient cohort in treatment remission. Single-cell RNA sequencing (scRNA-seq) was employed to identify differential signaling pathway expression in muscle biopsy samples from two patients with JDM and healthy controls. Immunohistochemistry was used to examine differences in STAT3 phosphorylation between JDM and control muscle tissues. In vitro, skeletal muscle cell lines were stimulated with IL-6, and the transcription levels of genes related to mitochondrial calcium channels were quantified via reverse transcription-polymerase chain reaction (RT-PCR). Reactive oxygen species (ROS) production was measured in both IL-6 treated and untreated groups. ROS levels were then compared between IL-6 receptor antagonist pre-treated skeletal muscle cells and untreated cells.IL-6 levels in newly onset patients with JDM were significantly higher compared to the same patient cohort in remission states (p < 0.0001). Serum IL-6 was significantly increased in patients with negative myositis specific antibody (MSA), positive melanoma differentiation associated protein 5 (MDA5) and positive nuclear matrix protein 2 (NXP2), yet not for JDM with positive transcriptional intermediary factor γ (TIF1γ), based on subgroup analysis. ScRNA-seq analysis of muscle biopsies from patients with MDA5-positive JDM and patients with MSA negative JDM revealed abnormal activation of the JAK/STAT3 pathway in skeletal myocytes, macrophages, and vascular endothelial cells. The phosphorylation levels of STAT3 were elevated in active JDM cases. Transcription of the calcium channel modulation gene sarcolipin (SLN) was significantly higher in JDM primary skeletal muscle cells compared to normal cells. In vitro, IL-6 enhanced SLN transcription and induced ROS production, and blocking the IL-6 receptor resulted in decreased ROS generation in skeletal muscle cells.IL-6/JAK/STAT3 signaling pathway was abnormally activated in patients with JDM. IL-6 may be involved in the pathogenesis of muscle damage by triggering the development of calcium overload and production of ROS. Blockade of the IL-6/JAK/STAT3 pathway can be a potential treatment option for JDM, especially MDA5-positive patients and those who are negative for MSA. [ABSTRACT FROM AUTHOR]

Linker-of-nucleoskeleton-and-cytoskeleton (LINC) complexes are conserved molecular bridges within the nuclear envelope that mediate mechanical force transmission into the nucleoplasm. The core of a LINC complex is formed by a transluminal interaction between the outer and inner nuclear membrane KASH and SUN proteins, respectively. Mammals encode six KASH proteins and five SUN proteins. Recently, KASH proteins were shown to bind to the domain interfaces of trimeric SUN2 proteins in vitro. However, neither the existence of SUN2 trimers in living cells nor the extent to which other SUN proteins conform to this assembly state have been tested experimentally. Here we extend the application of fluorescence fluctuation spectroscopy to quantify SUN protein oligomerization in the nuclear envelopes of living cells. Using this approach, we demonstrate for the first time that SUN2 trimerizes in vivo and we demonstrate that the in vivo oligomerization of SUN1 is not limited to a trimer. In addition, we provide evidence to support the existence of potential regulators of SUN protein oligomerization in the nuclear envelope. The differential SUN protein oligomerization illustrated here suggests that SUN proteins may have evolved to form different assembly states in order to participate in diverse mechanotransduction events.

The cellular response to hypoxia, in addition to HIF-dependent transcriptional reprogramming, also involves less characterized transcription-independent processes, such as alternative splicing of the VEGFA transcript leading to the production of the proangiogenic VEGF form. We now show that this event depends on reorganization of the splicing machinery, triggered after short-term hypoxia by ROS production and intranuclear redistribution of the nucleoskeletal proteins SAFB1/2. Exposure to low oxygen causes fast dissociation of SAFB1/2 from the nuclear matrix, which is reversible, inhibited by antioxidant treatment, and also observed under normoxia when the mitochondrial electron transport chain is blocked. This is accompanied by altered interactions between SAFB1/2 and the splicing machinery, translocation of kinase SRPK1 to the cytoplasm, and dephosphorylation of RS-splicing factors. Depletion of SAFB1/2 under normoxia phenocopies the hypoxic and ROS-mediated switch in VEGF mRNA splicing. These data suggest that ROS-dependent remodeling of the nuclear architecture can promote production of splicing variants that facilitate adaptation to hypoxia.

The article talks about recent studies that have focused primarily on neuromodulatory factors and circuits that promote aggression and dominance; reported genetic and neural substrates that are associated with suppression of aggression that have not been directly linked to social experience. Focuses on the study that found that the neuronal transcription regulator nervy (nvy) plays a key role in the social experience–dependent suppression of aggression.

Neutrino properties such as the Majorana nature and the masses, which go beyond the standard model, are derived from the experimental double-beta decay (DBD) rate by using the DBD nuclear matrix element (NME). Theoretical evaluations for the NME, however, are very difficult. Single-charge exchange reactions (SCERs) and double-charge exchange reactions (DCERs) are used to study nuclear isospin (τ) and spin (σ) correlations involved in the DBD NME and to theoretically calculate the DBD NME. Single and double τ σ NMEs for quasi-particle states are studied by SCERs and DCER. They are found to be reduced with respect to the quasi-particle model NMEs due to the τ σ correlations. The impact of the SCER- and DCER-NMEs on the DBD NME is discussed. [ABSTRACT FROM AUTHOR]

Electron backscatter diffraction (EBSD) has been used for more than 30 years for analyzing the structure of minerals and artificial substances. In recent times, EBSD has been widely applied for investigation of irradiated nuclear fuel and matrices for the immobilization of radioactive waste. The combination of EBSD and scanning electron microscopy (SEM/EDS) methods allows researchers to obtain simultaneously data on a specimen's local composition and structure. The article discusses the abilities of SEM/EDS and EBSD techniques to identify zirconolite polytype modifications and members of the polysomatic murataite–pyrochlore series in polyphase ceramic matrices, with simulations of Pu (Th) and the REE-actinide fraction (Nd) of high-level radioactive waste. [ABSTRACT FROM AUTHOR]

In this paper, we propose an efficient numerical computation method of reduced-order controller design for linear time-invariant systems. The design problem is described by linear matrix inequalities (LMIs) with a rank constraint on a structured matrix, due to which the problem is non-convex. Instead of the heuristic method that approximates the matrix rank by the nuclear norm, we propose a numerical projection onto the rank-constrained set based on the alternating direction method of multipliers (ADMM). Then the controller is obtained by alternating projection between the rank-constrained set and the LMI set. We show the effectiveness of the proposed method compared with existing heuristic methods, by using 95 benchmark models from the COMPL e ib library. [ABSTRACT FROM AUTHOR]

Whether the neutrino mass ordering is normal or inverted remains an experimentally open issue in neutrino physics. The knowledge of neutrino mass ordering has great importance for neutrinoless double-beta ( 0 ν β β ) decay experiments, which can establish the nature of massive neutrinos, i.e., whether they are Dirac or Majorana fermions. Recently, the KamLAND-Zen 800 measurement has reached for the first time the parameter space of the inverted ordering with a vanishing lightest neutrino mass. By assuming the inverted ordering, we attempt to derive the physical information of the neutrino nature and Majorana CP phases from a negative or positive observation of 0 ν β β decays in the near future. Moreover, the possibility of extracting the nuclear matrix element in the case of a positive observation is also examined.To avoid the ambiguity from unknown priors of neutrino masses, we adopt the maximum likelihood method instead of the Bayesian approach usually considered in previous works. [ABSTRACT FROM AUTHOR]

Context: Premature ovarian insuffciency (POI) affects 1% to 3.7% of women at reproductive age, and its etiology is heterogeneous. The linker of nucleoskeleton and cytoskeleton (LINC) complex, consisting of KASH5 and SUN1, plays an indispensable role in meiotic homolog pairing, determining the ovarian reserve. However, their roles in the pathogenesis of POI are unknown. Objective: To investigate the role of KASH5 variation in the pathogenesis of POI. Design: Whole-exome sequencing was performed in a pedigree with 2 POI patients. The pathogenicity of identifed variant was illustrated by in vitro functional studies, and its effect on ovarian function and meiosis was confrmed by histological analysis and oocyte spreads with Kash5 C-terminal deleted mice model. Results: A homozygous splicing site variant in KASH5 (c.747G > A) was identifed. In vitro studies found the variant disturbed the nuclear membrane localization of KASH5 and its binding with SUN1. Moreover, the Kash5 C-terminal deleted mice revealed defective meiotic homolog pairing and accelerated depletion of oocytes. Conclusions: The splicing site variant in KASH5 is responsible for POI due to defective meiotic homolog pairing and accelerated depletion of oocytes. Our study is the frst to report disorganized LINC complex participating in POI pathogenesis, potentially suggesting the essential roles of meiotic telomere attachment and dynein-driven proteins for chromosome movement in ovarian function maintenance. [ABSTRACT FROM AUTHOR]

The 2021 Summer Biomechanics, Bioengineering, and Biotransport Conference (SB3C) featured a workshop titled “The Elephant in the Room: Nuclear Mechanics and Mechanobiology.” The goal of this workshop was to provide a perspective from experts in the field on the current understanding of nuclear mechanics and its role in mechanobiology. This paper reviews the major themes and questions discussed during the workshop, including historical context on the initial methods of measuring the mechanical properties of the nucleus and classifying the primary structures dictating nuclear mechanics, physical plasticity of the nucleus, the emerging role of the linker of nucleoskeleton and cytoskeleton (LINC) complex in coupling the nucleus to the cytoplasm and driving the behavior of individual cells and multicellular assemblies, and the computational models currently in use to investigate the mechanisms of gene expression and cell signaling. Ongoing questions and controversies, along with promising future directions, are also discussed. [ABSTRACT FROM AUTHOR]

The large arrays of cell types in a multicellular organism are defined by their stereotypic size and/or morphology, and, for cells in vivo , by their anatomic positions. Historically, this identity–structure–function correlation was conceptualized as arising from distinct gene expression programs that dictate how cells appear and behave. However, a growing number of studies suggest that a cell's mechanical state is also an important determinant of its identity, both in lineage-committed cells and in pluripotent stem cells. Defining the mechanism by which mechanical inputs influence complex cellular programs remains an area of ongoing investigation. Here, we discuss how the cytoskeleton actively participates in instructing the response of the nucleus and genome to integrate mechanical and biochemical inputs, with a primary focus on the role of the actomyosin–LINC (linker of nucleoskeleton and cytoskeleton) complex axis. Cells can sense intrinsic and extrinsic mechanical inputs through indirect and direct pathways. Linker of nucleoskeleton and cytoskeleton (LINC) complexes are a conduit for direct mechanotransduction. Mechanical state impacts cell identity and fate decisions both in lineage-committed progenitors and pluripotent stem cells. Resetting the cellular mechanical state is a key step in induced pluripotent stem-cell reprogramming. Further developments in tools for robustly measuring intracellular mechanical forces will be critical to advance our understanding of the molecular mechanisms of mechanotransduction. [ABSTRACT FROM AUTHOR]

The need of large-scale chromatin organization in the nucleus has become more and more appreciated. The higher order nuclear organization ultimately regulate a plethora of biological processes including transcription, DNA replication, and DNA repair. In this context, it is of critical importance to understand the mechanisms that allow higher order nuclear organization. Scaffold Attachment Factor A (SAF-A/hnRNPU), which was originally identified as the component of nuclear matrix, has emerged as an important regulator of higher order nuclear organization. It is shown that SAF-A/hnRNPU binds to tandem repeats (TRs) and scaffold/matrix attachment regions (S/MAR) in a sequence-non-specific, but structure-specific manner (e.g. DNA curvature). Recent studies showed that SAF-A interacts with chromatin-associated RNAs (caRNAs) to regulate interphase chromatin structures in a transcription-dependent manner. It is proposed that SAF-A/hnRNPU and caRNAs form a dynamic, transcriptionally responsive chromatin mesh that organizes chromatin in a large scale. The common structural features of S/MAR and pericentromeric (periCEN) TR promotes SAF-A-mediated association with each other. Collectively a model is presented wherein SAF-A/hnRNPU and periCEN TR are the key players in large-scale nuclear organization that supports general transcription. [ABSTRACT FROM AUTHOR]

The possibilities of the further development of synchrotron Mössbauer radiation sources are considered. The pure nuclear diffraction of synchrotron radiation in a resonant nuclear matrix, in our case, in an iron borate (57FeBO3) crystal is a physical basis for the generation of synchrotron Mössbauer radiation. The coherent fluorescence of nuclei excited by synchrotron radiation results in the formation of a highly directional beam of polarized resonant gamma rays, which is used in unique fields of Mössbauer spectroscopy. The pure nuclear diffraction of gamma rays in the iron borate crystal near the Néel point, where the crystal has a strongly anisotropic nuclear polarizability, has been numerically simulated. The simulation has demonstrated that the intensity of synchrotron Mössbauer radiation sources can be significantly increased (for existing characteristics of accelerator centers) by using asymmetric conditions of Bragg diffraction and the appropriate polarization of radiation that excites nuclei. The results obtained in this work can be applied to develop high-resolution spectroscopy on synchrotron sources. [ABSTRACT FROM AUTHOR]

The article reviews the development of ideas on the domain organization of eukaryotic genome, with special attention on the studies of DNA loops anchored to the nuclear matrix and their role in the emergence of the modern model of eukaryotic genome spatial organization. Critical analysis of results demonstrating that topologically associated chromatin domains are structural-functional blocks of the genome supports the notion that these blocks are fundamentally different from domains whose existence was proposed by the domain hypothesis of eukaryotic genome organization formulated in the 1980s. Based on the discussed evidence, it is concluded that the model postulating that eukaryotic genome is built from uniformly organized structural-functional blocks has proven to be untenable. [ABSTRACT FROM AUTHOR]

This article is a tribute to Ron Hancock, a scientist known for his work in the field of biochemistry. Hancock began his career studying prokaryotic systems before shifting his focus to the eukaryotic cell nucleus and conducting research on chromatin and DNA replication. He made important contributions to the understanding of chromatin replication and high-order chromatin packaging, particularly in relation to the role of topoisomerase II. Hancock also explored the role of entropic forces in the assembly of nuclear compartments and chromatin folding. The author of the article had the opportunity to work with Hancock and describes him as a passionate and dedicated scientist who was always willing to help others. [Extracted from the article]

Cells sense and integrate external information from diverse sources that include mechanical cues. Shaping of tissues during development may thus require coordination between mechanical forces from morphogenesis and cell-cell signalling to confer appropriate changes in gene expression. By live-imaging Notch-induced transcription in real time, we have discovered that morphogenetic movements during Drosophila gastrulation bring about an increase in activity-levels of a Notch-responsive enhancer. Mutations that disrupt the timing of gastrulation resulted in concomitant delays in transcription up-regulation that correlated with the start of mesoderm invagination. As a similar gastrulation-induced effect was detected when transcription was elicited by the intracellular domain NICD, it cannot be attributed to forces exerted on Notch receptor activation. A Notch-independent vnd enhancer also exhibited a modest gastrulation-induced activity increase in the same stripe of cells. Together, these observations argue that gastrulation-associated forces act on the nucleus to modulate transcription levels. This regulation was uncoupled when the complex linking the nucleoskeleton and cytoskeleton (LINC) was disrupted, indicating a likely conduit. We propose that the coupling between tissue-level mechanics, arising from gastrulation, and enhancer activity represents a general mechanism for ensuring correct tissue specification during development and that Notch-dependent enhancers are highly sensitive to this regulation. [ABSTRACT FROM AUTHOR]

Regulation of chromatin structure and accessibility determines the transcription activities of genes, which endows the host with function-specific patterns of gene expression. Upon viral infection, the innate immune responses provide the first line of defense, allowing rapid production of variegated antiviral cytokines. Knowledge on how chromatin accessibility is regulated during host defense against viral infection remains limited. Our previous work found that the nuclear matrix protein SAFA surveilled viral RNA and regulated antiviral immune genes expression. However, how SAFA regulates the specific induction of antiviral immune genes remains unknown. Here, through integration of RNA-seq, ATAC-seq and ChIP-seq assays, we found that the depletion of SAFA specifically decreased the chromatin accessibility, activation and expression of virus induced genes. And mutation assays suggested that the RNA-binding ability of SAFA was essential for its function in regulating antiviral chromatin accessibility. RIP-seq results showed that SAFA exclusively bound with antiviral related RNAs following viral infection. Further, we combined the CRISPR-Cas13d mediated RNA knockdown system with ATAC-qPCR, and demonstrated that the binding between SAFA and according antiviral RNAs specifically mediated the openness of the corresponding chromatin and following robust transcription of antiviral genes. Moreover, knockdown of these associated RNAs dampened the accessibility of related genes in an extranuclear signaling pathway dependent manner. Interestingly, VSV infection cleaved SAFA protein at the C-terminus which deprived its RNA binding ability for immune evasion. Thus, our results demonstrated that SAFA and the interacting RNA products collaborated and remodeled chromatin accessibility to facilitate antiviral innate immune responses. Author summary: Regulation of chromatin opening and gene expression underlies a key point during host defense against viral infection, which endows the host with timely and effective antiviral gene expression patterns. We previously reported that the nuclear matrix protein SAFA surveils viral RNA and regulates antiviral immune genes expression. However, how SAFA regulates the expression and what determines the specific induction of antiviral immune genes remains unclear. Here, we used a combination of high-throughput sequencing technologies and found that SAFA and the interacting RNA products collaborated and specifically remodeled chromatin accessibility to facilitate antiviral immune genes expression. We also found that VSV infection cleaved SAFA protein at the C-terminus and deprived its RNA binding ability for immune evasion. Our study provides new insights into the mechanism by which chromatin remodeling facilitates the induction of antiviral immune genes. [ABSTRACT FROM AUTHOR]

Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear protein U (hnRNP U), is a ubiquitous nuclear scaffold protein that was implicated in XIST RNA localization to the inactive X-chromosome (Xi) but also reported to maintain open DNA packaging in euchromatin. Here we use several means to perturb SAF-A and examine potential impacts on the broad association of RNAs on euchromatin, and on chromatin compaction. SAF-A has an N-terminal DNA binding domain and C-terminal RNA binding domain, and a prominent model has been that the protein provides a single-molecule bridge between XIST RNA and chromatin. Here analysis of the impact of SAF-A on broad RNA-chromatin interactions indicate greater biological complexity. We focus on SAF-A's role with repeat-rich C0T-1 hnRNA (repeat-rich heterogeneous nuclear RNA), shown recently to comprise mostly intronic sequences of pre-mRNAs and diverse long non-coding RNAs (lncRNAs). Our results show that SAF-A mutants cause dramatic changes to cytological chromatin condensation through dominant negative effects on C0T-1 RNA's association with euchromatin, and likely other nuclear scaffold factors. In contrast, depletion of SAF-A by RNA interference (RNAi) had no discernible impact on C0T-1 RNA, nor did it cause similarly marked chromatin changes as did three different SAF-A mutations. Overall results support the concept that repeat-rich, chromatin-associated RNAs interact with multiple RNA binding proteins (RBPs) in a complex dynamic meshwork that is integral to larger-scale chromatin architecture and collectively influences cytological-scale DNA condensation. [ABSTRACT FROM AUTHOR]

The nuclear envelope (NE) has emerged as a nexus for cellular organization, signaling, and survival. Beyond its role as a barrier to separate the nucleoplasm from the cytoplasm, the NE's role in supporting and maintaining a myriad of other functions has made it a target of study in many cellular processes, including senescence. The nucleus undergoes dramatic changes in senescence, many of which are driven by changes in the NE. Indeed, Lamin B1, a key NE protein that is consistently downregulated in senescence, has become a marker for senescence. Other NE proteins have also been shown to play a role in senescence, including LINC (linker of nucleoskeleton and cytoskeleton) complex proteins. LINC complexes span the NE, forming physical connections between the cytoplasm to the nucleoplasm. In this way, they integrate nuclear and cytoplasmic mechanical signals and are essential not only for a variety of cellular functions but are needed for cell survival. However, LINC complex proteins have been shown to have a myriad of functions in addition to forming a LINC complex, often existing as nucleoplasmic or cytoplasmic soluble proteins in a variety of isoforms. Some of these proteins have now been shown to play important roles in DNA repair, cell signaling, and nuclear shape regulation, all of which are important in senescence. This review will focus on some of these roles and highlight the importance of LINC complex proteins in senescence. [ABSTRACT FROM AUTHOR]

Eukaryotic cells carry a vast amount of DNA packaged in their nucleus as chromatin. During cell division, it further condenses into individual Chromosomes. The basic unit of chromatin is nucleosome which comprises 200 bp of DNA wrapped around an octamer of positively charged histone proteins (2 molecules each H2A, H2B, H3, and H4), and one molecule of Histone H1. The octamer forms a cylinder around which DNA is wrapped (∼146 bp/octamer) and continues to the similar adjacent unit (∼60 bp of linker DNA), forming a string of nucleosomes. The H1 histone brings nucleosomes closer by binding with the linker DNA. These 10–11 nm thick threads further condense into 30 nm fibres, achieving a higher level of compaction by binding with nonhistone chromosomal proteins (e.g., topoisomerase II, condensins and cohesins) to form a scaffold through which the 30 nm fibre passes, forming loops. The average size of the loops is 600 nm, each accommodating approximately 60 kb of DNA. Whereas 85% of DNA is distributed in the loops, about 15% is associated with the scaffolds. The chromatin which is condensed even at interphase is 'heterochromatin'. Constitutive heterochromatin comprises tandem repeats of short DNA sequences and is generally devoid of genes, transcription and recombination. A potentially active part of the genome forms the 'euchromatin', which also has a differential distribution of DNA that shows up as mutually exclusive G- and R-bands rich in tissue-specific and housekeeping genes, highlighting a highly organised compaction of DNA in the chromatin. Compared to these bands, >100 kb long 'topologically associating domains' (TADs) have been identified at the genome level as the functional unit of chromatin. For its differential functional states, chromatin constantly undergoes condensation and decondensation, mediated by the post-translational modification of histones (e.g. acetylation, methylation of lysine) and the displacement of nucleosomes by an ATP-dependent complex of proteins (e.g. SWI/SNF). DNA methylation is another mode of chromatin modification that affects chromatin function. Thus, a highly dynamic system of chromatin organisation not only encapsulates a large amount of DNA in the nucleus but ensures differential gene function in an orderly fashion. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of preoperative urinary nuclear matrix protein 22 (NMP22) and Cystatin B (CSTB) expressions in evaluating the postoperative recurrence of bladder cancer.Methods: The clinical case data of 102 patients with bladder cancer who underwent surgical treatment from January 2017 to January 2022 were collected, and the patients were divided into a recurrence group (n = 54) and nonrecurrence group (n = 48) according to whether the patients recurred after surgery, and the preoperative NMP22 and CSTB expression levels between the two groups were compared. Receiver operating curve (ROC) was used to analyze the evaluation value of preoperative NMP22 and CSTB expression in patients with bladder cancer postoperative recurrence. Logistic multivariate regression method was used to analyze the correlation between preoperative NMP22 and CSTB expression and postoperative bladder cancer recurrence. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of NMP22 and CSTB single detection and combined detection were evaluated for postoperative recurrence of bladder cancer.Results: The preoperative expression levels of NMP22 and CSTB in the recurrence group were significantly higher than those in the nonrecurrence group (P < 0.05). The results of ROC curve analysis showed that the AUC of preoperative NMP22 and CSTB expression levels to assess postoperative recurrence of bladder cancer was 0.696 and 0.659, respectively (P < 0.05). Logistic multivariate regression analysis showed that preoperative NMP22 and CSTB overexpression was an independent risk factor for postoperative recurrence of bladder cancer (OR = 1.042, 2.307, P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of preoperative NMP22 combined with CSTB in evaluating bladder cancer recurrence after surgery were higher than those of preoperative NMP22 and CSTB alone, and the differences were statistically significant (P < 0.05).Conclusion: Preoperative NMP22 and CSTB conveying is hardly interrelated to postoperative recurrence of bladder carcinoma and has certain appraisal worth for postoperative recurrence of bladder carcinoma, and the combined testing of the two has a taller appraisal worth. NMP22 combined with CSTB detection will help to detect postoperative recurrence of bladder cancer and formulate effective treatment measures in time. [ABSTRACT FROM AUTHOR]

Simple Summary: Speckles and other nuclear bodies, the nucleolus and perinucleolar zone, transcription/replication factories and the lamina-associated compartment, serve as a structural basis for various genomic functions. In turn, genome activity and specific chromatin 3D organization directly impact the integrity of intranuclear assemblies, initiating/facilitating their formation and dictating their composition. Thus, the large-scale nucleus structure and genome activity mutually influence each other. The cell nucleus is frequently considered a compartment in which the genome is placed to protect it from external forces. Here, we discuss the evidence demonstrating that the cell nucleus should be considered, rather, as structure built around the folded genome. Decondensing chromosomes provide a scaffold for the assembly of the nuclear envelope after mitosis, whereas genome activity directs the assembly of various nuclear compartments, including nucleolus, speckles and transcription factories. The cell nucleus is frequently considered a cage in which the genome is placed to protect it from various external factors. Inside the nucleus, many functional compartments have been identified that are directly or indirectly involved in implementing genomic DNA's genetic functions. For many years, it was assumed that these compartments are assembled on a proteinaceous scaffold (nuclear matrix), which provides a structural milieu for nuclear compartmentalization and genome folding while simultaneously offering some rigidity to the cell nucleus. The results of research in recent years have made it possible to consider the cell nucleus from a different angle. From the "box" in which the genome is placed, the nucleus has become a kind of mobile exoskeleton, which is formed around the packaged genome, under the influence of transcription and other processes directly related to the genome activity. In this review, we summarize the main arguments in favor of this point of view by analyzing the mechanisms that mediate cell nucleus assembly and support its resistance to mechanical stresses. [ABSTRACT FROM AUTHOR]

Beta decay in hydrogen-like atoms is studied under the influence of a linearly polarized laser field. The oscillating electronic cloud under an intense laser field produces a time-varying field around the nucleus. The interaction of this electric field with the nucleus of the hydrogenic system is studied in terms of interaction between the electronic and nuclear charge densities. The nuclear transition matrix for beta decay is calculated by considering the interaction Hamiltonian, and the variations in the decay constant are analyzed. [ABSTRACT FROM AUTHOR]

During the early meiotic prophase, connections are established between chromosomes and cytoplasmic motors via a nuclear envelope bridge, known as a LINC (linker of nucleoskeleton and cytoskeleton) complex. These widely conserved links can promote both chromosome and nuclear motions. Studies in diverse organisms have illuminated the molecular architecture of these connections, but important questions remain regarding how they contribute to meiotic processes. Here, we summarize the current knowledge in the field, outline the challenges in studying these chromosome dynamics, and highlight distinctive features that have been characterized in major model systems. [ABSTRACT FROM AUTHOR]

Herpesviruses assemble new viral particles in the nucleus. These nucleocapsids bud through the inner nuclear membrane to produce enveloped viral particles in the perinuclear space before fusing with the outer nuclear membrane to reach the cytoplasm. This unusual route is necessary since viral capsids are too large to pass through nuclear pores. However, the transient perinuclear nucleocapsids (250 nm in diameter) are also larger than the width of the perinuclear space (30 to 50 nm). Interestingly, linker of the nucleoskeleton and cytoskeleton (LINC) components SUN and KASH connect the inner and outer nuclear membranes and regulate their spacing. Previous work by others on the related pseudorabies virus and human cytomegalovirus showed that they functionally interact with SUN proteins. To clarify the role of SUN proteins, we explored their impact on herpes simplex virus 1 (HSV-1), another herpesvirus. Using dominant negative SUN mutants and RNA interference, we show that HSV-1 propagation is dependent on the LINC complex. In contrast to pseudorabies virus, SUN2 disruption by either approach led to increased HSV-1 extracellular viral yields. This SUN2 dependency may be linked to its greater impact on perinuclear spacing in infected cells compared to SUN1. Finally, the virus itself seems to modulate perinuclear spacing. [ABSTRACT FROM AUTHOR]

The sperm nucleus of the decapod crustacean Chinese mitten crab, Eriocheir sinensis, is loose and fibrous, which is a non-condensed nucleus. Our purpose was to analyze the structural distribution of the fusome-related protein Add1 during the spermatogenesis in E. sinensis to better understand the non-condensed nucleus of E. sinensis. RT-qPCR and western blot results showed that Add1 was expressed at the transcriptional and translational level during spermatogenesis of E. sinensis. Immunofluorescence results showed that Add1 was widely distributed in the process of spermatogenesis, including spermatogonia, spermatocytes, spermatids, and sperm. In the initial stage of sperm nucleus decondensation of E. sinensis, Add1 was widely expressed in the cytoplasm of spermatogonia. In the process from stage III spermatids to sperm, Add1 is mainly expressed in the nucleus. With the continuous differentiation of cells, Add1 gradually transferred from the cytoplasm to the nucleus. Our results indicated that the fusome-related protein Add1 might be involved in the spermiogenesis through the construction of a new nuclear skeleton to participate in the decondensation of sperm nuclei and the maintenance and protection of non-condensed chromatin. [ABSTRACT FROM AUTHOR]

Well-known theories of aging suggest that a certain metabolic defect negatively affects vital activity of the cell, be it oxidative stress, the accumulation of lesions in DNA, the exhaustion of telomeres, or distorted epigenetic processes. The theory of aging considered in the review postulates that an accumulation of progerin on the inner side of the nuclear envelope underlies the above defects. Progerin is a defective precursor of the lamin A nuclear matrix protein in which the C-terminal cysteine, which is removed normally, is retained and modified with a hydrophobic oligoisoprene chain. Progerin molecules attach with their hydrophobic processes to the inner membrane of the nuclear envelope, pushing away the adjacent fibrils of the nuclear matrix and the chromatin periphery. This changes the morphology and shape of the nucleus and alters the properties of the nuclear envelope and pore complexes embedded in it. As progerin accumulates in the nucleus, structural distortions increase in the nucleus, further distorting the nuclear–cytoplasmic transport of macromolecules and leading to the above defects in cell metabolism. This leads to increasing cell death and aging of the body over time. This mechanism of aging has been identified in patients with Hutchinson–Gilford progeria syndrome (HGPS). Mass progerin production in HGPS is caused by the point mutation c.1824C→T in exon 11 of the LMNA gene, which codes for lamins A and C. The mutation stimulates nonstandard splicing of the primary transcript during the formation of the lamin A precursor mRNA, thus causing progerin production. Children with progeria who have received the mutation from one of their parents age rapidly and die before 15 years of age. Approaches to progeria treatment are aimed at preventing the formation of progerin or destroying the progerin that has already accumulated. In the latter case, a promising strategy is to use rapamycin or its analogs and other substances and techniques that activate autophagy to purify the cell from progerin. Although in much smaller amounts, progerin is found in progeria-free people and may therefore play a role in natural aging. A maximum age that a person can reach is possible to estimate by taking account of the role that progerin plays in telomere shortening. Encouraging preliminary results achieved in purifying cells from progerin provide a means to develop an optimal procedure for periodic purification of the human body from progerin in order to reduce the rate of aging. [ABSTRACT FROM AUTHOR]