Mutations in genes encoding proteins associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex within the nuclear envelope cause different diseases with varying phenotypes including skeletal muscle, cardiac, metabolic, or nervous system pathologies. There is some understanding of the structure of LINC complex-associated proteins and how they interact, but it is unclear how mutations in genes encoding them can cause the same disease, and different diseases with different phenotypes. Here, published mutations in LINC complex-associated proteins were systematically reviewed and analyzed to ascertain whether patterns exist between the genetic sequence variants and clinical phenotypes. This revealed LMNA is the only LINC complex-associated gene in which mutations commonly cause distinct conditions, and there are no clear genotype-phenotype correlations. Clusters of LMNA variants causing striated muscle disease are located in exons 1 and 6, and metabolic disease-associated LMNA variants are frequently found in the tail of lamin A/C. Additionally, exon 6 of the emerin gene, EMD, may be a mutation \"hot-spot\", and diseases related to SYNE1, encoding nesprin-1, are most often caused by nonsense type mutations. These results provide insight into the diverse roles of LINC-complex proteins in human disease and provide direction for future gene-targeted therapy development.

The antimicrobial property of silver is associated to the quantity of silver and the grade of silver released. The ionized silver is extremely sensitive, as it binds to tissue proteins and gets operational alterations in the bacterial cell wall and nuclear membrane leading to cell modification and death.Silver nanoparticles have the talent to anchor to the bacterial cell wall and consequently infiltrate it, so causing physical modifications in the cell membrane like the absorptivity of the cell membrane and death of the cell. There are numerous concepts on the act of silver nanoparticle on bacteria to reason the microbicidal influence.

Numerous factors including chemical, hormonal, spatial, and physical cues determine stem cell fate. While the regulation of stem cell differentiation by soluble factors is well-characterized, the role of mechanical force in the determination of lineage fate is just beginning to be understood. Investigation of the role of force on cell function has largely focused on \"outside-in\" signaling, initiated at the plasma membrane. When interfaced with the extracellular matrix, the cell uses integral membrane proteins, such as those found in focal adhesion complexes to translate force into biochemical signals. Akin to these outside-in connections, the internal cytoskeleton is physically linked to the nucleus, via proteins that span the nuclear membrane. Although structurally and biochemically distinct, these two forms of mechanical coupling influence stem cell lineage fate and, when disrupted, often lead to disease. Here we provide an overview of how mechanical coupling occurs at the plasma and nuclear membranes. We also discuss the role of force on stem cell differentiation, with focus on the biochemical signals generated at the cell membrane and the nucleus, and how those signals influence various diseases. While the interaction of stem cells with their physical environment and how they respond to force is complex, an understanding of the mechanical regulation of these cells is critical in the design of novel therapeutics to combat diseases associated with aging, cancer, and osteoporosis. Stem Cells 2016;34:1455-1463.

Immunohistochemical staining (IHC) with emerin, an integral inner nuclear membrane protein, highlights nuclear membrane details in papillary thyroid carcinoma (PTC). We evaluated emerin for highlighting nuclear shape, grooves, inclusions, circumferential nuclear membrane irregularities (\"garlands\"), deep \"stellate\" membrane invaginations, and crescents in 34 fine-needle aspiration (FNA) cell blocks, PTC (n = 24) and follicular neoplasms (FN) (n = 10). Tissue microarrays were also examined for 182 cases, PTC (n = 95) and non-PTC (n = 87). Emerin IHC of PTC revealed a predominantly oval nuclear shape in the majority of cases, with FN demonstrating round nuclei and FV of PTC showing a roughly equal distribution of round and oval shapes. In addition to oval nuclear shape, the presence of emerin-positive nuclear grooves, circumferential emerin nuclear \"garlands,\" nuclear crescent shapes, and chromatin clearing on cell block H&E staining were significant predictors of PTC by regression analysis. Emerin IHC of thyroid FNA and surgical specimens serves as a useful adjunct to conventional H&E staining in the diagnosis of PTC and its distinction from FN by delineating diagnostic nuclear membrane irregularities (\"garlands\" and crescents), nuclear grooves, and a characteristic oval nuclear shape. In diagnostically challenging cases with limited cellularity, emerin staining can help to provide a more definitive diagnosis of PTC.

Nuclear margin irregularity is an important diagnostic feature of malignant cells. The exact cause of nuclear margin irregularity is not fully understood. The distortion of the nuclear envelope is probably the major factor in nuclear margin irregularity. Multiple proteins on the nuclear envelope, particularly nuclear lamin, are responsible for the distortion of the nuclear envelope. The extracellular matrix may also indirectly affect the nuclear position and shape by the closely connected network of actin-nespirin-SUN-lamin links. The alteration of nuclear matrix protein and RET-oncogene expression may play a role in nuclear envelope distortion and in margin irregularity. In this review, the probable causes and impact of nuclear margin irregularities are discussed.

The laminopathies are a diverse group of conditions caused by mutations in the LMNA gene (MIM*150330). LMNA encodes the nuclear envelope proteins lamin A and lamin C by utilization of an alternative splice site in exon 10. The human LMNA gene was identified in 1986 but it was another 13 years before it was found to be the causative gene for a disease, namely Emery Dreifuss muscular dystrophy. Since then, a further eight clearly defined phenotypes have been associated with LMNA mutations. The diversity of these phenotypes is striking with features such as premature ageing, axonal neuropathy, lipodystrophy and myopathy being seen. These phenotypes and the emerging genotype/phenotype correlations are the subject of this review.

Dilated cardiomyopathy is the most frequent cardiomyopathy. Twenty to 35% of dilated cardiomyopathies are familial. The transmission of the disease is most frequently dominant autosomic. Dilated cardiomyopathy is genetically heterogeneous. Hence, mutations have been identified on 14 genes, and 9 loci have been associated to familial dilated cardiomyopathy. The incriminated mechanisms in the pathogeny of dilated cardiomyopathy include mutations on proteins of the sarcomere, the cytosqueletton, the nuclear membrane or involved in calcium signaling. This review indicates the genes and proteins implicated in the pathogeny of familial dilated cardiomyopathy, and their potential clinical effects.

The lamina-associated polypeptide (LAP) 2 family comprises up to six alternatively spliced proteins in mammalian cells and three isoforms in Xenopus. LAP2beta is a type II integral protein of the inner nuclear membrane, which binds to lamin B and the chromosomal protein BAF, and may link the nuclear membrane to the underlying lamina and provide docking sites for chromatin. LAP2alpha shares only the N-terminus with the other isoforms and contains a unique C-terminus. It is a nonmembrane protein associated with the nucleoskeleton and may help to organize higher order chromatin structure by interacting with A-lamins and chromosomes. Recent studies using mutant proteins have just begun to unravel functions of LAP2 isoforms during postmitotic nuclear reassembly. LAP2alpha associates with chromosomes via an alpha-specific domain at early stages of assembly, possibly providing a structural framework for chromosome reorganization. The subsequent interaction of both LAP2alpha and LAP2beta with the chromosomal BAF may stabilize chromatin structure and target membranes to the chromosomes. At later stages LAP2 may regulate the assembly of lamins. LAP2 isoforms have been found to share a homologous approximately 40 amino acid long region, the LEM domain, with nuclear membrane proteins MAN1 and emerin, which has been implicated in Emery-Dreifuss muscular dystrophy.

The nuclear lamina is located between the inner nuclear membrane and the peripheral chromatin. It is composed of both peripheral and integral membrane proteins, including lamins and lamina-associated proteins. Lamins can interact with one another, with lamina-associated proteins, with nuclear scaffold proteins, and with chromatin. Likewise, most of the lamina-associated proteins are likely to interact directly with chromatin. The nuclear lamina is required for proper cell cycle regulation, chromatin organization, DNA replication, cell differentiation, and apoptosis. Mutations in proteins of the nuclear lamina can disrupt these activities and cause genetic diseases. The structure and assembly of the nuclear lamina proteins and their roles in chromatin organization and cell cycle regulation were recently reviewed. In this review, we discuss the roles of the nuclear lamina in DNA replication and apoptosis and analyze how mutations in nuclear lamina proteins might cause genetic diseases.

Pre-mRNA is transcribed primarily from genes located at the interface between chromatin domains and the interchromatin space. After partial or complete processing and complexing with nuclear proteins, the transcripts leave their site of synthesis and travel through the interchromatin space to the nuclear pores for export to the cytoplasm. It is unclear whether transcripts are tethered within the interchromatin space and move toward the nuclear pores using a metabolic energy-requiring, directed mechanism or, alternatively, move randomly by a diffusion-based process. We discuss here recent progress in understanding this step of gene expression, including our experiments tracking the movement of intranuclear poly(A) RNA in living cells. Our results and those of others are most consistent with a model in which newly synthesized mRNAs diffuse throughout the interchromatin space until they randomly encounter and are captured by the export machinery. Because the export machinery appears to preferentially bind transport-competent mRNAs (complexed with the correct complement of nuclear proteins), this diffusion-based model for intranuclear RNA movement potentially allows for a significant level of posttranscriptional control of gene expression.