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Fibroblast topology

Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Moein Yaqubi, Abdulshakour Mohammadnia
Ectopic expression of a defined set of transcription factors (TFs) can directly convert fibroblasts into a cardiac myocyte cell fate. Beside inefficiency in generating induced cardiomyocytes (iCMs), the molecular mechanisms that regulate this process remained to be well defined. The main purpose of this study was to provide better insight on the transcriptome regulation and to introduce a new strategy for candidating TFs for the transdifferentiation process. Eight mouse and three human high quality microarray data sets were analyzed to find differentially expressed genes (DEGs), which we integrated with TF-binding sites and protein-protein interactions to construct gene regulatory and protein-protein interaction networks...
August 31, 2016: Journal of Cellular Physiology
Vy T H Pham, Vi Khanh Truong, Anna Orlowska, Shahram Ghanaati, Mike Barbeck, Patrick Booms, Alex J Fulcher, Chris M Bhadra, Ričardas Buividas, Vladimir Baulin, C James Kirkpatrick, Pauline Doran, David E Mainwaring, Saulius Juodkazis, Russell J Crawford, Elena P Ivanova
With an aging population and the consequent increasing use of medical implants, managing the possible infections arising from implant surgery remains a global challenge. Here, we demonstrate for the first time that a precise nanotopology provides an effective intervention in bacterial cocolonization enabling the proliferation of eukaryotic cells on a substratum surface, preinfected by both live Gram-negative, Pseudomonas aeruginosa, and Gram-positive, Staphylococcus aureus, pathogenic bacteria. The topology of the model black silicon (bSi) substratum not only favors the proliferation of eukaryotic cells but is biocompatible, not triggering an inflammatory response in the host...
August 31, 2016: ACS Applied Materials & Interfaces
Akanksha Gupta, Rahul Agarwal, Ashutosh Singh, Sonika Bhatnagar
CONTEXT: Thrombospondin1 (TSP1) participates in numerous signaling pathways critical for vascular physiology and disease. The conserved signature domain of thrombospondin 1 (TSP1-Sig1) comprises three epidermal growth factor (EGF), 13 calcium-binding type 3 thrombospondin (T3) repeats, and one lectin-like module arranged in a stalk-wire-globe topology. TSP1 is known to be present in both calcium-replete (Holo-) and calcium-depleted (Apo-) state, each with distinct downstream signaling effects...
August 2, 2016: Journal of Receptor and Signal Transduction Research
Mario Novkovic, Lucas Onder, Jovana Cupovic, Jun Abe, David Bomze, Viviana Cremasco, Elke Scandella, Jens V Stein, Gennady Bocharov, Shannon J Turley, Burkhard Ludewig
Fibroblastic reticular cells (FRCs) form the cellular scaffold of lymph nodes (LNs) and establish distinct microenvironmental niches to provide key molecules that drive innate and adaptive immune responses and control immune regulatory processes. Here, we have used a graph theory-based systems biology approach to determine topological properties and robustness of the LN FRC network in mice. We found that the FRC network exhibits an imprinted small-world topology that is fully regenerated within 4 wk after complete FRC ablation...
July 2016: PLoS Biology
Yuan Shao, Tianyuan He, Gary J Fisher, John J Voorhees, Taihao Quan
OBJECTIVE: Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-aging effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of retinol anti-aging properties in naturally aged human skin in vivo. METHODS: Sun-protected buttock skin (76±6 years old, n=12) was topically treated with 0.4% ROL and its vehicle for seven days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR, and Western analysis...
June 4, 2016: International Journal of Cosmetic Science
Timothy Fee, Swetha Surianarayanan, Crawford Downs, Yong Zhou, Joel Berry
To examine the influence of substrate topology on the behavior of fibroblasts, tissue engineering scaffolds were electrospun from polycaprolactone (PCL) and a blend of PCL and gelatin (PCL+Gel) to produce matrices with both random and aligned nanofibrous orientations. The addition of gelatin to the scaffold was shown to increase the hydrophilicity of the PCL matrix and to increase the proliferation of NIH3T3 cells compared to scaffolds of PCL alone. The orientation of nanofibers within the matrix did not have an effect on the proliferation of adherent cells, but cells on aligned substrates were shown to elongate and align parallel to the direction of substrate fiber alignment...
2016: PloS One
Yong Chen, Yunfei Wang, Zhenyu Xuan, Min Chen, Michael Q Zhang
Defining chromatin interaction frequencies and topological domains is a great challenge for the annotations of genome structures. Although the chromosome conformation capture (3C) and its derivative methods have been developed for exploring the global interactome, they are limited by high experimental complexity and costs. Here we describe a novel computational method, called CITD, for de novo prediction of the chromatin interaction map by integrating histone modification data. We used the public epigenomic data from human fibroblast IMR90 cell and embryonic stem cell (H1) to develop and test CITD, which can not only successfully reconstruct the chromatin interaction frequencies discovered by the Hi-C technology, but also provide additional novel details of chromosomal organizations...
June 20, 2016: Nucleic Acids Research
Yanqiong Zhang, Xia Mao, Qiuyan Guo, Ming Bai, Bo Zhang, Chunfang Liu, Yanqun Sun, Shao Li, Na Lin
Traditional Chinese medicine (TCM) syndromes have been regarded as the crucial clinical manifestations for individualized diagnosis and treatment of complex diseases, including rheumatoid arthritis (RA) and cancer. Especially, RA patients are classified into cold and hot syndromes with different clinical manifestations, interventions and molecular mechanisms. Better effectiveness of a classic cold syndrome-specific herbal formula Wu-tou decoction (WTD) has been achieved. To explore molecular mechanisms of syndrome-specific formulae is of great clinical significance to improve the effectiveness and pertinence of treatment for the complex diseases with personalized conditions...
March 29, 2016: Oncotarget
Jessica S Martinez, Kristopher D Kelly, Yara E Ghoussoub, Jose D Delgado, Thomas C S Keller Iii, Joseph B Schlenoff
Polymers of various architectures with zwitterionic functionality have recently been shown to effectively suppress nonspecific fouling of surfaces by proteins and prokaryotic (bacteria) or eukaryotic (mammalian) cells as well as other microorganisms and environmental contaminants. In this work, zwitterionic copolymers were used to make thin coatings on substrates with the layer-by-layer method. Polyelectrolyte multilayers, PEMUs, were built with [poly(allylamine hydrochloride)], PAH, and copolymers of acrylic acid and either the AEDAPS zwitterionic group 3-[2-(acrylamido)-ethyldimethyl ammonio] propane sulfonate (PAA-co-AEDAPS), or benzophenone (PAABp)...
April 2016: Biomaterials Science
Huajie Bu, Giorgia Baraldo, Günter Lepperdinger, Pidder Jansen-Dürr
MicroRNAs (miRNAs) are a group of small non-coding executor RNAs. Their function as key modulators of cellular senescence has been widely recognized recently. By cross-comparing several human aging models we previously identified dozens of miRNAs being differentially regulated during aging. Here the functions of two miRNAs, mir-24 and mir-424, were investigated in an oxidative stress-induced fibroblast premature senescence model. Using pre-miRNA precursors, miRNAs were overexpressed in cells undergoing premature senescence induced by oxidative stress...
March 2016: Experimental Gerontology
Ole Jung, Ralf Smeets, Alexander Kopp, Dario Porchetta, Philipp Hiester, Max Heiland, Reinhard E Friedrich, Clarissa Precht, Henning Hanken, Alexander Gröbe, Philip Hartjen
BACKGROUND/AIM: Plasma electrolytic oxidation (PEO), also known as micro-arc oxidation, is a promising electrochemical surface treatment technique for metals which has been used for the generation of various material surfaces and has been the focus of recent biomaterial research. It has been hypothesized that rough PEO surfaces should generally have properties that support cellular attachment and proliferation. However, this has not yet been demonstrated in systematically conducted studies...
January 2016: In Vivo
C D Navo, F Corzana, E M Sánchez-Fernández, J H Busto, A Avenoza, M M Zurbano, E Nanba, K Higaki, C Ortiz Mellet, J M García Fernández, J M Peregrina
A series of conformationally locked C-glycosides based on the 3-aminopyrano[3,2-b]pyrrol-2(1H)-one (APP) scaffold has been synthesized. The key step involved a totally stereocontrolled C-Michael addition of a serine-equivalent C-nucleophile to tri-O-benzyl-2-nitro-D-galactal, previously published by the authors. Stereoselective transformations of the Michael adduct allowed us the synthesis of compounds with mono- or diantennated aglycone moieties and different topologies. In vitro screening showed highly selective inhibition of bovine liver β-glucosidase/β-galactosidase and specific inhibition of human β-glucocerebrosidase among lysosomal glycosidases for compounds bearing palmitoyl chains in the aglycone, with a marked dependence of the inhibition potency upon their number and location...
January 28, 2016: Organic & Biomolecular Chemistry
Nitasha Sehgal, Andrew J Fritz, Jaromira Vecerova, Hu Ding, Zihe Chen, Branislav Stojkovic, Sambit Bhattacharya, Jinhui Xu, Ronald Berezney
There is growing evidence that chromosome territories (CT) have a probabilistic non-random arrangement within the cell nucleus of mammalian cells including radial positioning and preferred patterns of interchromosomal interactions that are cell-type specific. While it is generally assumed that the three-dimensional (3D) arrangement of genes within the CT is linked to genomic regulation, the degree of non-random organization of individual CT remains unclear. As a first step to elucidating the global 3D organization (topology) of individual CT, we performed multi-color fluorescence in situ hybridization using six probes extending across each chromosome in human WI38 lung fibroblasts...
February 1, 2016: Human Molecular Genetics
Aurijit Sarkar, Umesh R Desai
Glycosaminoglycans (GAGs) affect human physiology and pathology by modulating more than 500 proteins. GAG-protein interactions are generally assumed to be ionic and nonspecific, but specific interactions do exist. Here, we present a simple method to identify the GAG-binding site (GBS) on proteins that in turn helps predict high specific GAG-protein systems. Contrary to contemporary thinking, we found that the electrostatic potential at basic arginine and lysine residues neither identifies the GBS consistently, nor its specificity...
2015: PloS One
Noemi Cavaletto, Anna Luganini, Giorgio Gribaudo
UNLABELLED: The human cytomegalovirus (HCMV) US12 gene family includes a group of 10 contiguous genes (US12 to US21) encoding predicted seven-transmembrane-domain (7TMD) proteins that are nonessential for replication within cultured fibroblasts. Nevertheless, inactivation of some US12 family members affects virus replication in other cell types; e.g., deletion of US16 or US18 abrogates virus growth in endothelial and epithelial cells or in human gingival tissue, respectively, suggesting a role for some US12 proteins in HCMV cell tropism...
November 2015: Journal of Virology
Xulun Zhang, Chunjiang J Yu, Sangram S Sisodia
BACKGROUND: The γ-secretase complex, composed of transmembrane proteins termed presenilin (PS), anterior pharynx defective (APH), nicastrin (NCT), and presenilin enhancer-2 (Pen-2) catalyzes intramembranous hydrolysis of a variety of Type I membrane protein substrates. In order to understand aspects of subunit assembly, interactions, dynamics and catalysis, it is essential to clarify the membrane topology of each polypeptide. Hydophathicity plots predict that the 101 amino acid Pen-2 molecule has two hydrophobic domains (HP1 and HP2) that may serve as transmembrane spanning domains...
2015: Molecular Neurodegeneration
Sarvenaz Sarabipour, Nuala Del Piccolo, Kalina Hristova
Here we describe an experimental tool, termed quantitative imaging Förster resonance energy transfer (QI-FRET), that enables the quantitative characterization of membrane protein interactions. The QI-FRET methodology allows us to acquire binding curves and calculate association constants for complex membrane proteins in the native plasma membrane environment. The method utilizes FRET detection, and thus requires that the proteins of interest are labeled with florescent proteins, either FRET donors or FRET acceptors...
August 18, 2015: Accounts of Chemical Research
Hendrik Marks, Hindrik H D Kerstens, Tahsin Stefan Barakat, Erik Splinter, René A M Dirks, Guido van Mierlo, Onkar Joshi, Shuang-Yin Wang, Tomas Babak, Cornelis A Albers, Tüzer Kalkan, Austin Smith, Alice Jouneau, Wouter de Laat, Joost Gribnau, Hendrik G Stunnenberg
BACKGROUND: During early embryonic development, one of the two X chromosomes in mammalian female cells is inactivated to compensate for a potential imbalance in transcript levels with male cells, which contain a single X chromosome. Here, we use mouse female embryonic stem cells (ESCs) with non-random X chromosome inactivation (XCI) and polymorphic X chromosomes to study the dynamics of gene silencing over the inactive X chromosome by high-resolution allele-specific RNA-seq. RESULTS: Induction of XCI by differentiation of female ESCs shows that genes proximal to the X-inactivation center are silenced earlier than distal genes, while lowly expressed genes show faster XCI dynamics than highly expressed genes...
2015: Genome Biology
Minseong Kim, GeunHyung Kim
Micro/nanofibrous structures have been applied widely in various tissue-engineering applications because the topological structures are similar to the extracellular matrix (ECM), which encourages a high degree of cell adhesion and growth. However, it has been difficult to produce a three-dimensional (3D) fibrous structure using controllable macro-pores. Recently, cellulose has been considered a high-potential natural-origin biomaterial, but its use in 3D biomedical structures has been limited due to its narrow processing window...
November 1, 2015: Journal of Colloid and Interface Science
Darío G Lupiáñez, Katerina Kraft, Verena Heinrich, Peter Krawitz, Francesco Brancati, Eva Klopocki, Denise Horn, Hülya Kayserili, John M Opitz, Renata Laxova, Fernando Santos-Simarro, Brigitte Gilbert-Dussardier, Lars Wittler, Marina Borschiwer, Stefan A Haas, Marco Osterwalder, Martin Franke, Bernd Timmermann, Jochen Hecht, Malte Spielmann, Axel Visel, Stefan Mundlos
Mammalian genomes are organized into megabase-scale topologically associated domains (TADs). We demonstrate that disruption of TADs can rewire long-range regulatory architecture and result in pathogenic phenotypes. We show that distinct human limb malformations are caused by deletions, inversions, or duplications altering the structure of the TAD-spanning WNT6/IHH/EPHA4/PAX3 locus. Using CRISPR/Cas genome editing, we generated mice with corresponding rearrangements. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus...
May 21, 2015: Cell
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