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nuclear architecture

Soya Shinkai, Tadasu Nozaki, Kazuhiro Maeshima, Yuichi Togashi
The mammalian genome is organized into submegabase-sized chromatin domains (CDs) including topologically associating domains, which have been identified using chromosome conformation capture-based methods. Single-nucleosome imaging in living mammalian cells has revealed subdiffusively dynamic nucleosome movement. It is unclear how single nucleosomes within CDs fluctuate and how the CD structure reflects the nucleosome movement. Here, we present a polymer model wherein CDs are characterized by fractal dimensions and the nucleosome fibers fluctuate in a viscoelastic medium with memory...
October 2016: PLoS Computational Biology
Naomi Winn, Radhesh Lalam, Victor Cassar-Pullicino
Paget's disease of bone is a disorder of bone remodelling, leading to changes in the architecture and overall appearance of the bone. The disorder may be monostotic or polyostotic and affect any bone in the body, although most commonly it involves the spine, pelvis, skull and femur. This article explores the different imaging modalities used in the assessment of Paget's disease of bone in its different phases. The relative merits of each imaging modality is discussed with illustrative examples, in particular with respect to radiographs, nuclear medicine bone scan, computed tomography (CT) and magnetic resonance imaging (MRI)...
October 19, 2016: Wiener Medizinische Wochenschrift
Emilie Lukasova, Aleš Kovařík, Alena Bačíková, Martin Falk, Stanislav Kozubek
The cellular transition to senescence is associated with extensive chromatin reorganization and gene expression changes. Recent studies appeared implying an association of lamin B1 (LB1) reduction with chromatin rearrangement in human fibroblasts promoted to senescence, while the mechanisms and structural features of these relations were not yet clarified. In this work we examined the functions of LB1 and lamin B receptor (LBR) in human cancer cells. We found that both LB1 and LBR tend to deplete during cancer cells transfer to senescence by γ-irradiation...
October 19, 2016: Biochemical Journal
Luca Giorgetti, Edith Heard
Chromosome conformation capture (3C)-based techniques have revolutionized the field of nuclear organization, partly replacing DNA FISH as the method of choice for studying three-dimensional chromosome architecture. Although DNA FISH is commonly used for confirming 3C-based findings, the two techniques are conceptually and technically different and comparing their results is not trivial. Here, we discuss both 3C-based techniques and DNA FISH approaches to highlight their similarities and differences. We then describe the technical biases that affect each approach, and review the available reports that address their compatibility...
October 19, 2016: Genome Biology
Clara Lopes Novo, Peter J Rugg-Gunn
Pluripotent cells are characterized by a globally open and accessible chromatin organization that is thought to contribute to cellular plasticity and developmental decision-making. We recently identified the pluripotency factor Nanog as a key regulator of this form of chromatin architecture in mouse embryonic stem cells. In particular, we demonstrated that the transcription factors Nanog and Sall1 co-dependently mediate the epigenetic state of pericentromeric heterochromatin to reinforce a more open and accessible organization in pluripotent cells...
October 19, 2016: Nucleus
George Taylor-Walker, Savannah A Lynn, Eloise Keeling, Rosie Munday, David A Johnston, Anton Page, Jennifer A Scott, Srini Goverdhan, Andrew J Lotery, J Arjuna Ratnayaka
Age-related Macular Degeneration (AMD) is a common, irreversible blinding condition that leads to the loss of central vision. AMD has a complex aetiology with both genetic as well as environmental risks factors, and share many similarities with Alzheimer's disease. Recent findings have contributed significantly to unravelling its genetic architecture that is yet to be matched by molecular insights. Studies are made more challenging by observations that aged and AMD retinas accumulate the highly pathogenic Alzheimer's-related Amyloid beta (Aβ) group of peptides, for which there appears to be no clear genetic basis...
October 14, 2016: Experimental Eye Research
Haifeng Teng, Meng Chen, Ansheng Zou, Haili Jiang, Jichun Han, Long Sun, Chao Feng, Ju Liu
OBJECTIVES: The objective of this study was to investigate the hepatoprotective effect of licochalcone B (LCB) in a mice model of carbon tetrachloride (CCl4)-induced liver toxicity. MATERIALS AND METHODS: Hepatotoxicity was induced in mice by a single subcutaneous injection (SC) of CCl4. The LCB was administered orally once a day for seven days (PO) as pretreatment at three doses of 1, 5, and 25 mg/kg/day. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA...
August 2016: Iranian Journal of Basic Medical Sciences
Raf Donders, Kathleen Sanen, Rik Paesen, Eli Slenders, Wilfried Gyselaers, Piet Stinissen, Marcel Ameloot, Niels Hellings
In situ detection of MSCs remains difficult and warrants additional methods to aid with their characterization in vivo. Two-photon confocal laser scanning microscopy (TPM) and second harmonic generation (SHG) could fill this gap. Both techniques enable the detection of cells and extracellular structures, based on intrinsic properties of the specific tissue and intracellular molecules under optical irradiation. TPM imaging and SHG imaging have been used for label-free monitoring of stem cells differentiation, assessment of their behavior in biocompatible scaffolds, and even cell tracking in vivo...
2016: Stem Cells International
S F Lax
The 2014 World Health Organization (WHO) classification of uterine tumors revealed simplification of the classification by fusion of several entities and the introduction of novel entities. Among the multitude of alterations, the following are named: a simplified classification for precursor lesions of endometrial carcinoma now distinguishes between hyperplasia without atypia and atypical hyperplasia, the latter also known as endometrioid intraepithelial neoplasia (EIN). For endometrial carcinoma a differentiation is made between type 1 (endometrioid carcinoma with variants and mucinous carcinoma) and type 2 (serous and clear cell carcinoma)...
October 13, 2016: Der Pathologe
Kevin J Tsai, Mei-Yeh Jade Lu, Kai-Jung Yang, Mengyun Li, Yuchuan Teng, Shihmay Chen, Maurice S B Ku, Wen-Hsiung Li
The diploid C4 plant foxtail millet (Setaria italica L. Beauv.) is an important crop in many parts of Africa and Asia for the vast consumption of its grain and ability to grow in harsh environments, but remains understudied in terms of complete genomic architecture. To date, there have been only two genome assembly and annotation efforts with neither assembly reaching over 86% of the estimated genome size. We have combined de novo assembly with custom reference-guided improvements on a popular cultivar of foxtail millet and have achieved a genome assembly of 477 Mbp in length, which represents over 97% of the estimated 490 Mbp...
October 13, 2016: Scientific Reports
Andrea D Merg, Jennifer C Boatz, Abhishek Mandal, Gongpu Zhao, Soumitra Mokashi-Punekar, Chong Liu, Xianting Wang, Peijun Zhang, Patrick C A van der Wel, Nathaniel L Rosi
Chiral nanoparticle assemblies are an interesting class of materials whose chiroptical properties make them attractive for a variety of applications. Here, C18-(PEPAu(M-ox))2 (PEPAu(M-ox) = AYSSGAPPM(ox)PPF) is shown to direct the assembly of single-helical gold nanoparticle superstructures that exhibit exceptionally strong chiroptical activity at the plasmon frequency with absolute g-factor values up to 0.04. Transmission electron microscopy (TEM) and cryogenic electron tomography (cryo-ET) results indicate that the single helices have a periodic pitch of approximately 100 nm and consist of oblong gold nanoparticles...
October 11, 2016: Journal of the American Chemical Society
Ilenia Pellarin, Laura Arnoldo, Silvia Costantini, Silvia Pegoraro, Gloria Ros, Carlotta Penzo, Gianluca Triolo, Francesca Demarchi, Riccardo Sgarra, Alessandro Vindigni, Guidalberto Manfioletti
The HMGA1 architectural transcription factor is an oncogene overexpressed in the vast majority of human cancers. HMGA1 is a highly connected node in the nuclear molecular network and the key aspect of HMGA1 involvement in cancer development is that HMGA1 simultaneously confers cells multiple oncogenic hits, ranging from global chromatin structural and gene expression modifications up to the direct functional alterations of key cellular proteins. Interestingly, HMGA1 also modulates DNA damage repair pathways...
2016: PloS One
Sergio Guerrero-Castillo, Fabian Baertling, Daniel Kownatzki, Hans J Wessels, Susanne Arnold, Ulrich Brandt, Leo Nijtmans
Mitochondrial complex I is the largest integral membrane enzyme of the respiratory chain and consists of 44 different subunits encoded in the mitochondrial and nuclear genome. Its biosynthesis is a highly complicated and multifaceted process involving at least 14 additional assembly factors. How these subunits assemble into a functional complex I and where the assembly factors come into play is largely unknown. Here, we applied a dynamic complexome profiling approach to elucidate the assembly of human mitochondrial complex I and its further incorporation into respiratory chain supercomplexes...
September 30, 2016: Cell Metabolism
Constantin Cretu, Jana Schmitzová, Almudena Ponce-Salvatierra, Olexandr Dybkov, Evelina I De Laurentiis, Kundan Sharma, Cindy L Will, Henning Urlaub, Reinhard Lührmann, Vladimir Pena
SF3b is a heptameric protein complex of the U2 small nuclear ribonucleoprotein (snRNP) that is essential for pre-mRNA splicing. Mutations in the largest SF3b subunit, SF3B1/SF3b155, are linked to cancer and lead to alternative branch site (BS) selection. Here we report the crystal structure of a human SF3b core complex, revealing how the distinctive conformation of SF3b155's HEAT domain is maintained by multiple contacts with SF3b130, SF3b10, and SF3b14b. Protein-protein crosslinking enabled the localization of the BS-binding proteins p14 and U2AF65 within SF3b155's HEAT-repeat superhelix, which together with SF3b14b forms a composite RNA-binding platform...
October 20, 2016: Molecular Cell
Tommaso Bizzarro, Maurizio Martini, Sara Capodimonti, Patrizia Straccia, Celestino Pio Lombardi, Alfredo Pontecorvi, Luigi Maria Larocca, Esther Diana Rossi
BACKGROUND: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a challenge for the diagnosis and management of thyroid carcinoma. Some authors have proposed histological criteria that are able to distinguish NIFTPs from invasive follicular variant of papillary thyroid carcinoma (I-FVPTC). Hence, NIFTPs may have repercussions in the diagnostic categories on fine-needle aspiration. In the current study, the authors evaluated the criteria for NIFTPs on liquid-based cytology samples...
October 2016: Cancer
Ngoc Thien Lam, Timothy J Muldoon, Kyle P Quinn, Narasimhan Rajaram, Kartik Balachandran
The role of valvular interstitial cell (VIC) architecture in regulating cardiac valve function and pathology is not well understood. VICs are known to be more elongated in a hypertensive environment compared to those in a normotensive environment. We have previously reported that valve tissues cultured under hypertensive conditions are prone to acute pathological alterations in cell phenotype and contractility. We therefore aimed to rigorously study the relationship between VIC shape, contractile output and other functional indicators of VIC pathology...
October 10, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Zhijie Liang, Dongdi Zhang, Haiying Wang, Pengtao Ma, Zongfei Yang, Jingyang Niu, Jingping Wang
[H4Ni10(H2O)8Nb32O102](20-), representing the first high-nuclear nickel-cation-bridged polyoxoniobate, has been synthesized. It incorporates two [{Ni2O4}(H2O)2(Nb6O19)](12-) and two [Ni3(H2O)2Nb10O34](12-) subunits exhibiting a rhombus-like architecture. Furthermore, the solution behaviour was examined by electrospray ionization mass spectrometry and the magnetic properties in the low temperature range indicate the presence of ferromagnetic interactions.
October 18, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Chaitra Parthiban, Dhanasekaran Varudharasu, Mayilvahanan Shanmugam, Prerna Gopal, Chandran Ragunath, Leonard Thomas, Mark Nitz, Narayanan Ramasubbu
The oral pathogen, Aggregatibacter actinomycetemcomitans, uses pga gene locus for the production of an exopolysaccharide made up of a linear homopolymer of β-1,6-N-acetyl-D-glucosamine (PGA). An enzyme encoded by the pgaB of the pga operon in A. actinomycetemcomitans is a de-N-acetylase which is used to alter the PGA. The full length enzyme (AaPgaB) and the N-terminal catalytic domain (residues 25-290, AaPgaBN) from A. actinomycetemcomitans were cloned, expressed and purified. The enzymatic activities of the AaPgaB enzymes were determined using 7-acetoxycoumarin-3-carboxylic acid as the substrate...
October 5, 2016: Molecular Oral Microbiology
Sepideh Khorasanizadeh, Fraydoon Rastinejad
Nuclear receptors (NRs) are master regulators of broad genetic programs in metazoans. These programs are regulated in part by the small-molecule ligands that bind NRs and modulate their interactions with transcriptional coregulatory factors. X-ray crystallography is now delivering more complete pictures of how the multi-domain architectures of NR homo- and heterodimers are physically arranged on their DNA elements, and how ligands and coactivator peptides act through these complexes. Complementary studies are also pointing to a variety of novel mechanisms by which NRs access their DNA response elements within chromatin...
October 5, 2016: Endocrinology
J Stephen Dumler, Sara H Sinclair, Valeria Pappas-Brown, Amol C Shetty
Anaplasma phagocytophilum, an obligate intracellular prokaryote, infects neutrophils, and alters cardinal functions via reprogrammed transcription. Large contiguous regions of neutrophil chromosomes are differentially expressed during infection. Secreted A. phagocytophilum effector AnkA transits into the neutrophil or granulocyte nucleus to complex with DNA in heterochromatin across all chromosomes. AnkA binds to gene promoters to dampen cis-transcription and also has features of matrix attachment region (MAR)-binding proteins that regulate three-dimensional chromatin architecture and coordinate transcriptional programs encoded in topologically-associated chromatin domains...
2016: Frontiers in Cellular and Infection Microbiology
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