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nuclear architecture

Jason K H Lai, Michelle M Collins, Veronica Uribe, Vanesa Jiménez-Amilburu, Stefan Günther, Hans-Martin Maischein, Didier Y R Stainier
Cardiac trabeculation is a highly regulated process that starts with the delamination of compact layer cardiomyocytes. The Hippo signaling pathway has been implicated in cardiac development but many questions remain. We have investigated the role of Wwtr1, a nuclear effector of the Hippo pathway, in zebrafish and find that its loss leads to reduced cardiac trabeculation. However, in mosaic animals, wwtr1-/- cardiomyocytes contribute more frequently than wwtr1+/- cardiomyocytes to the trabecular layer of wild-type hearts...
May 17, 2018: Development
Jarish N Cohen, Jessica A Spies, Fawn Ross, Angela Bohlke, Timothy H McCalmont
Heavily pigmented melanocytic neoplasms are genotypically and phenotypically diverse. Recently, a subset of this histopathologic spectrum was shown to harbor recurrent genetic alterations in the gene-encoding protein kinase A regulatory subunit-α (PRKAR1A). To date, no histopathologic descriptions of melanomas arising from this pathway have been described. We present a case of a darkly pigmented papule arising on the posterior neck of a 28-year-old man. Microscopically, the heavily pigmented compound melanocytic proliferation was centered in the dermis with permeation into the superficial subcutis...
May 16, 2018: American Journal of Dermatopathology
Mostafa R Fayed, Reem N El-Naga, El-Sayed Akool, Ebtehal El-Demerdash
Liver fibrosis results from chronic inflammation that precipitates excessive accumulation of extracellular matrix. Oxidative stress is involved in its pathogenesis. This study aimed to elucidate the potential antifibrotic effect of the NADPH oxidase (NOX) inhibitor, apocynin against concanavalin A (ConA)-induced immunological model of liver fibrosis, and to investigate the ability of the antioxidant, alpha-lipoic acid (α-LA) to potentiate this effect. Rats were treated with apocynin and/or α-LA for six weeks...
2018: Drug Discoveries & Therapeutics
Young Jun Choi, Jung Hwan Baek, Jung Hee Shin, Woo Hyun Shim, Seon-Ok Kim, Won-Hong Lee, Dong Eun Song, Tae Yong Kim, Ki-Wook Chung, Jeong Hyun Lee
BACKGROUND: The purpose of this study was to construct a web-based predictive model using ultrasound characteristics and subcategorized biopsy results for thyroid nodules of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) to stratify the risk of malignancy. METHODS: Data included 672 thyroid nodules from 656 patients from a historical cohort. We analyzed ultrasound images of thyroid nodules and biopsy results according to nuclear atypia and architectural atypia...
May 13, 2018: Head & Neck
Alexander Klimovich, Arvid Rehm, Jörg Wittlieb, Eva-Maria Herbst, Ricardo Benavente, Thomas C G Bosch
The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra . We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization...
May 10, 2018: Aging
Vidhya Krishnamoorthy, Richa Khanna, Veena K Parnaik
Lamins constitute the major architectural proteins of the nuclear lamina that help in maintaining nuclear organization. Mutations in lamins are associated with diverse degenerative diseases, collectively termed laminopathies. HECW2, a HECT-type E3 ubiquitin ligase, is transcriptionally upregulated in HeLa cells expressing Emery-Dreifuss muscular dystrophy-causing-lamin A mutants. However, the role of HECW2 upregulation in mediating downstream effects in lamin mutant-expressing cells was previously unexplored...
May 10, 2018: Biochimica et Biophysica Acta
Eun-Bee Park, Joo-Yeong Jeon, Chang-Jin Jeon
A growing number of studies have revealed the functional neuroarchitecture of the microbat retina and suggested that microbats can see using their eyes. To better understand the organization of the microbat retina, quantitative analysis of protein kinase C alpha (PKCα)- and tyrosine hydroxylase (TH)-immunoreactive (IR) cells was conducted on the greater horseshoe bat (Rhinolophus ferrumequinum) retina. As a result, PKCα immunoreactivity was observed in rod bipolar cells, consistent with previous studies on other mammalian retinas...
May 9, 2018: Histology and Histopathology
Tingting Duan, Pamela K Geyer
Drosophila Suppressor of Hairy-wing [Su(Hw)] protein is an example of a multivalent transcription factor. Although best known for its role in establishing the chromatin insulator of the gypsy retrotransposon, Su(Hw) functions as an activator and repressor at non- gypsy genomic sites. It remains unclear how the different regulatory activities of Su(Hw) are utilized during development. Motivated from observations of spatially restricted expression of Su(Hw) in the testis, we investigated the role of Su(Hw) in spermatogenesis to advance an understanding of its developmental contributions as an insulator, repressor and activator protein...
May 8, 2018: Genetics
Parvaiz Ahmad Shiekh, Anamika Singh, Ashok Kumar
With the advancement in biomaterial sciences, tissue engineered scaffolds are developing as a promising strategy for the regeneration of damaged tissues. However, only a few of these scaffolds have been translated into clinical applications. One of the primary drawbacks of the existing scaffolds is the lack of adequate oxygen supply within the scaffolds. Oxygen producing biomaterials have been developed as an alternate strategy but are faced with two major concerns. One is controlling the rate of oxygen generation, and the other is the production of reactive oxygen species...
May 8, 2018: ACS Applied Materials & Interfaces
Valérie Lallemand-Breitenbach, Hugues de Thé
PML nuclear bodies are nucleated by the PML protein, which polymerizes into spherical shells where it concentrates many unrelated partner proteins. Emerging data has connected PML bodies to post-translational control, notably conjugation by SUMOs. High concentrations of SUMO-bound proteins were proposed to condense into liquid-like droplets and such phase transition may occur within NBs. Many stress pathways modulate NB formation and recent findings have directly implicated PML in oxidative stress response in vivo...
April 30, 2018: Current Opinion in Cell Biology
Laurent Bianchetti, Bianca Wassmer, Audrey Defosset, Anna Smertina, Marion L Tiberti, Roland H Stote, Annick Dejaegere
BACKGROUND: Nuclear hormone receptors (NRs) constitute a large family of multi-domain ligand-activated transcription factors. Dimerization is essential for their regulation, and both DNA binding domain (DBD) and ligand binding domain (LBD) are implicated in dimerization. Intriguingly, the glucocorticoid receptor-α (GRα) presents a DBD dimeric architecture similar to that of the homologous estrogen receptor-α (ERα), but an atypical dimeric architecture for the LBD. The physiological relevance of the proposed GRα LBD dimer is a subject of debate...
April 30, 2018: Biochimica et Biophysica Acta
Mariana Lomiento, Fabiana Mammoli, Emilia Maria Cristina Mazza, Silvio Bicciato, Sergio Ferrari
Human myelopoiesis is an intriguing biological process during which multipotent stem cells limit their differentiation potential generating precursors that evolve into terminally differentiated cells. The differentiation process is correlated with differential gene expression and changes in nuclear architecture. In interphase, chromosomes are distinct entities known as chromosome territories and they show a radial localization that could result in a constrain of inter-homologous distance. This element plays a role in genome stability and gene expression...
March 2, 2018: Hematology Reports
Eric J Montemayor, Allison L Didychuk, Allyson D Yake, Gurnimrat K Sidhu, David A Brow, Samuel E Butcher
The spliceosome removes introns from precursor messenger RNA (pre-mRNA) to produce mature mRNA. Prior to catalysis, spliceosomes are assembled de novo onto pre-mRNA substrates. During this assembly process, U6 small nuclear RNA (snRNA) undergoes extensive structural remodeling. The early stages of this remodeling process are chaperoned by U6 snRNP proteins Prp24 and the Lsm2-8 heteroheptameric ring. We now report a structure of the U6 snRNP from Saccharomyces cerevisiae. The structure reveals protein-protein contacts that position Lsm2-8 in close proximity to the chaperone "active site" of Prp24...
May 1, 2018: Nature Communications
Ke Fang, Xuecheng Chen, Xiaowei Li, Yi Shen, Jielin Sun, Daniel M Czajkowsky, Zhifeng Shao
It is widely recognized that the higher-order spatial organization of the genome, beyond the nucleosome, plays an important role in many biological processes. However, to date, direct information of even such fundamental structural details as the typical sizes and DNA content of these higher-order structures in situ is poorly characterized. Here, we examine the nanoscopic DNA organization within human nuclei using super-resolution direct stochastic optical reconstruction microscopy (dSTORM) imaging and 5-ethynyl-2'-deoxyuridine (EdU) click chemistry, studying single fully-labeled chromosomes within an otherwise unlabeled nuclei to improve the attainable resolution...
May 1, 2018: ACS Nano
Xiao-Tong Wang, Qiu-Yuan Xia, Sheng-Bing Ye, Xuan Wang, Rui Li, Ru Fang, Shan-Shan Shi, Ru-Song Zhang, Xiao Tan, Jie-Yu Chen, Ke Sun, Xiao-Dong Teng, Heng-Hui Ma, Zhen-Feng Lu, Xiao-Jun Zhou, Qiu Rao
Both Xp11 translocation renal cell carcinomas and the corresponding mesenchymal neoplasms are characterized by a variety of gene fusions involving TFE3. It has been known that tumors with different gene fusions may have different clinicopathologic features; however, further in-depth investigations of subtyping Xp11 translocation-associated cancers are needed in order to explore more meaningful clinicopathologic correlations. A total of 22 unusual cases of Xp11 translocation-associated cancers were selected for the current study; 20 cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners...
April 30, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Hai-Bin Ruan, Peter A Crawford
PURPOSE OF REVIEW: Ketone body metabolism is a dynamic and integrated metabolic node in human physiology, whose roles include but extend beyond alternative fuel provision during carbohydrate restriction. Here we discuss the most recent observations suggesting that ketosis coordinates cellular function via epigenomic regulation. RECENT FINDINGS: Ketosis has been linked to covalent modifications, including lysine acetylation, methylation, and hydroxybutyrylation, to key histones that serve as dynamic regulators of chromatin architecture and gene transcription...
April 24, 2018: Current Opinion in Clinical Nutrition and Metabolic Care
Longping V Tse, Sven Moller-Tank, Rita M Meganck, Aravind Asokan
Adeno-associated viruses (AAV) encode a unique assembly activating protein (AAP) within their genome that is essential for capsid assembly. Studies to date have focused on establishing the role of AAP as a chaperone that mediates stability, nucleolar transport, and assembly of AAV capsid proteins. Here, we map structure-function correlates of AAP using secondary structure analysis followed by deletion and substitutional mutagenesis of specific domains, namely, the hydrophobic N-terminal domain (HR), conserved core (CC), proline-rich region (PRR), threonine/serine rich region (T/S) and basic region (BR)...
April 25, 2018: Journal of Virology
Noemi Molina, Angela Martin-Serrano, Tahia D Fernandez, Amene Tesfaye, Francisco Najera, María J Torres, Cristobalina Mayorga, Yolanda Vida, Maria I Montañez, Ezequiel Perez-Inestrosa
Dendrimeric Antigens (DeAns) consist of dendrimers decorated with multiple units of drug antigenic determinants. These conjugates have been shown to be a powerful tool for diagnosing penicillin allergy using in vitro immunoassays, in which they are recognized by specific IgE from allergic patients. Here we propose a new diagnostic approach using DeAns in cellular tests, in which recognition occurs through IgE bound to the basophil surface. Both IgE molecular recognition and subsequent cell activation may be influenced by the tridimensional architecture and size of the immunogens...
April 24, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Edilane Rodrigues Dantas de Araújo, Gerlane Coelho Bernardo Guerra, Daline Fernandes de Souza Araújo, Aurigena Antunes de Araújo, Júlia Morais Fernandes, Raimundo Fernandes de Araújo Júnior, Valéria Costa da Silva, Thaís Gomes de Carvalho, Leandro de Santis Ferreira, Silvana Maria Zucolotto
Kalanchoe brasiliensis and Kalanchoe pinnata are used interchangeably in traditional medicine for treating peptic ulcers and inflammatory problems. In this context, this study aims to characterize the chemical constituents and evaluate the gastroprotective activity of the leaf juices of the two species in acute gastric lesions models. Thin Layer Chromatography (TLC) and Ultra High Performance Liquid Chromatography coupled to Mass Spectrometer (UHPLC-MS) were performed for chemical characterization. Wistar rats were pre-treated orally with leaf juices (125, 250 and 500 mg/kg) or ranitidine (50 mg/kg)...
April 24, 2018: International Journal of Molecular Sciences
Lisha Zheng, Jingyi Jiang, Jinpeng Gui, Lingyu Zhang, Xiaoyi Liu, Yan Sun, Yubo Fan
The periodontal ligament (PDL) is highly ordered connective tissue located between the alveolar bone and cementum. An aligned and organized architecture is required for its physiological function. We applied micropatterning technology to arrange PDL cells in 10- or 20-μm-wide extracellular protein patterns. Cell and nuclear morphology, cytoskeleton, proliferation, differentiation, and matrix metalloproteinase system expression were investigated. Micropatterning clearly elongated PDL cells with a low cell-shape index and low spreading area...
April 24, 2018: Biophysical Journal
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