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https://www.readbyqxmd.com/read/28077629/sun2-silencing-impairs-cd4-t-cell-proliferation-and-alters-sensitivity-to-hiv-1-infection-independently-of-cyclophilin-a
#1
Daniel A Donahue, Françoise Porrot, Norbert Couespel, Olivier Schwartz
: Linker of nucleoskeleton and cytoskeleton (LINC) complexes connect the nucleus to the cytoskeleton in eukaryotic cells. We previously reported that overexpression of SUN2, an inner nuclear membrane protein and LINC complex component, inhibits HIV infection between reverse transcription and nuclear import in a capsid-specific manner. We also reported that SUN2 silencing does not modulate HIV infection in several cell lines. Silencing of SUN2 was recently reported to decrease HIV infection of CD4 T cells, an effect suggested to result from modulation of CypA-dependent steps of HIV infection...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28071740/elucidating-the-modes-of-action-for-bioactive-compounds-in-a-cell-specific-manner-by-large-scale-chemically-induced-transcriptomics
#2
Michio Iwata, Ryusuke Sawada, Hiroaki Iwata, Masaaki Kotera, Yoshihiro Yamanishi
The identification of the modes of action of bioactive compounds is a major challenge in chemical systems biology of diseases. Genome-wide expression profiling of transcriptional responses to compound treatment for human cell lines is a promising unbiased approach for the mode-of-action analysis. Here we developed a novel approach to elucidate the modes of action of bioactive compounds in a cell-specific manner using large-scale chemically-induced transcriptome data acquired from the Library of Integrated Network-based Cellular Signatures (LINCS), and analyzed 16,268 compounds and 68 human cell lines...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069634/a-review-of-connectivity-map-and-computational-approaches-in-pharmacogenomics
#3
Aliyu Musa, Laleh Soltan Ghoraie, Shu-Dong Zhang, Galina Galzko, Olli Yli-Harja, Matthias Dehmer, Benjamin Haibe-Kains, Frank Emmert-Streib
Large-scale perturbation databases, such as Connectivity Map (CMap) or Library of Integrated Network-based Cellular Signatures (LINCS), provide enormous opportunities for computational pharmacogenomics and drug design. A reason for this is that in contrast to classical pharmacology focusing at one target at a time, the transcriptomics profiles provided by CMap and LINCS open the door for systems biology approaches on the pathway and network level. In this article, we provide a review of recent developments in computational pharmacogenomics with respect to CMap and LINCS and related applications...
January 9, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28060557/control-of-nuclear-organization-by-f-actin-binding-proteins
#4
Karin Pfisterer, Asier Jayo, Maddy Parsons
The regulation of nuclear shape and deformability is a key factor in controlling diverse events from embryonic development to cancer cell metastasis, but the mechanisms governing this process are still unclear. Our recent study demonstrated an unexpected role for the F-actin bundling protein fascin in controlling nuclear plasticity through a direct interaction with Nesprin-2. Nesprin-2 is a component of the LINC complex that is known to couple the F-actin cytoskeleton to the nuclear envelope. We demonstrated that fascin, which is predominantly associated with peripheral F-actin rich filopodia, binds directly to Nesprin-2 at the nuclear envelope in a range of cell types...
January 6, 2017: Nucleus
https://www.readbyqxmd.com/read/28057128/-expression-and-function-of-long-intergenic-non-protein-coding-rna-regulator-of-reprogramming-in-high-grade-ovarian-serous-cancer
#5
H H Jiang, Y H Lou, X Y Wang, Y Han, Z M Cui
Objective: To investigate the expression of long intergenic non-protein coding RNA-regulator of reprogramming (Linc-ROR) in high-grade ovarian serous cancer, and explore the relationship between Linc-ROR expression and biological function of high-grade ovarian serous cancer. Methods: A total of 34 high-grade ovarian serous cancer tissue samples and 19 normal fallopian tube tissue samples were collected between June 2014 and February 2016. Real-time reverse transcription (RT)-PCR was used to detect the Linc-ROR mRNA expression in different samples...
December 25, 2016: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/28053048/identifying-new-antiepileptic-drugs-through-genomics-based-drug-repurposing
#6
Nasir Mirza, Greame J Sills, Munir Pirmohamed, Anthony G Marson
Currently available antiepileptic drugs (AEDs) fail to control seizures in 30% of patients. Genomics-based drug repurposing (GBR) offers the potential of savings in the time and cost of developing new AEDs. In the current study, we used published data and software to identify the transcriptomic signature of chornic temporal lobe epilepsy and the drugs that reverse it. After filtering out compounds based on exclusion criteria, such as toxicity, 36 drugs were retained. 11 of the 36 drugs identified (>30%) have published evidence of antiepileptic efficacy (for example, curcumin) or antiepileptogenic affect (for example, atorvastatin) in recognised rodent models or patients...
January 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28049722/the-linc-complex-contributes-to-heterochromatin-organisation-and-transcriptional-gene-silencing-in-plants
#7
Axel Poulet, Céline Duc, Maxime Voisin, Sophie Desset, Sylvie Tutois, Emmanuel Vanrobays, Matthias Benoit, David E Evans, Aline V Probst, Christophe Tatout
The LInker of Nucleoskeleton and Cytoskeleton (LINC) complex is an evolutionary well-conserved protein bridge connecting the cytoplasmic and nuclear compartments across the nuclear membrane. While recent data support its function in nuclear morphology and meiosis, its implication in chromatin organisation has not been studied in plants. Here 3D imaging methods have been used to investigate nuclear morphology and chromatin organisation in interphase nuclei of the model plant Arabidopsis thaliana, in which heterochromatin cluster in conspicuous chromatin domains called chromocentres...
January 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28035049/opposing-roles-for-distinct-linc-complexes-in-regulation-of-the-small-gtpase-rhoa
#8
Ketan Thakar, Christopher K May, Anna Rogers, Christopher W Carroll
Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA. A key effector in this process is the transcription factor/coactivator complex composed of SRF/Mkl1...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27999969/functions-of-long-intergenic-non-coding-linc-rnas-in-plants
#9
Masashi Yamada
Whole transcriptome analyses in many organisms have revealed that most transcribed RNAs do not encode proteins. These non-coding RNAs likely contribute to the regulation of gene expression during the development of multicellular organisms. In eukaryotes, the roles of small RNAs, one class of non-coding RNAs, in transcriptional and post-transcriptional regulation have been well characterized. However, the functions of a second class of non-coding RNAs, long intergenic noncoding (linc) RNAs, are relatively unknown, especially in plants...
January 2017: Journal of Plant Research
https://www.readbyqxmd.com/read/27992983/risk-factors-for-hepatitis-c-virus-infection-in-the-colombian-caribbean-coast-a-case-control-study
#10
Ismael de Jesús Yepes, Beatriz Lince, Clara Caez, Giovanni De Vuono
INTRODUCTION: An estimated 6.8-8.9 million people are infected with hepatitis C virus in Latin America, of which less than 1% receives antiviral treatment. Studies so far in Colombia have attempted to determine the prevalence of the disease in some risk groups, thus preventing the identification of other factors potentially involved in the spread of the infection. OBJECTIVES: To identify traditional and non-traditional risk factors for chronic hepatitis C in the Colombian Caribbean coast...
December 1, 2016: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/27979987/altered-nuclear-dynamics-in-mdx-myofibers
#11
Shama R Iyer, Sameer B Shah, Ana P Valencia, Martin F Schneider, Erick O Hernandez-Ochoa, Joseph P Stains, Silvia S Blemker, Richard M Lovering
Duchenne muscular dystrophy (DMD) is a genetic disorder in which the absence of dystrophin leads to progressive muscle degeneration and weakness. While the genetic basis is known, the pathophysiology of dystrophic skeletal muscle remains unclear. We examined nuclear movement in wild type (WT) and dystrophin-null (MDX) mouse myofibers. We also examined expression of proteins in the LINC (linkers of nucleoskeleton and cytoskeleton) complex as well as nuclear transcriptional activity via histone H3 acetylation and polyadenylate-binding nuclear protein-1...
December 15, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27974481/unc-84-linc-ing-chromosome-movement-and-double-strand-break-repair
#12
Nicola Silva, Verena Jantsch
Assaults to our DNA take place at a high frequency and are incompatible with life. In this issue, Lawrence et al. (2016. J. Cell Biol https://doi.org/10.1083/jcb.201604112) demonstrate that a novel complex links the nucleus with cytoplasmic microtubules for the promotion of DNA repair by homologous recombination.
December 19, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27956467/linc-complexes-promote-homologous-recombination-in-part-through-inhibition-of-nonhomologous-end-joining
#13
Katherine S Lawrence, Erin C Tapley, Victor E Cruz, Qianyan Li, Kayla Aung, Kevin C Hart, Thomas U Schwartz, Daniel A Starr, JoAnne Engebrecht
The Caenorhabditis elegans SUN domain protein, UNC-84, functions in nuclear migration and anchorage in the soma. We discovered a novel role for UNC-84 in DNA damage repair and meiotic recombination. Loss of UNC-84 leads to defects in the loading and disassembly of the recombinase RAD-51. Similar to mutations in Fanconi anemia (FA) genes, unc-84 mutants and human cells depleted of Sun-1 are sensitive to DNA cross-linking agents, and sensitivity is rescued by the inactivation of nonhomologous end joining (NHEJ)...
December 19, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27936041/recreating-stable-brachypodium-hybridum-allotetraploids-by-uniting-the-divergent-genomes-of-b-distachyon-and-b-stacei
#14
Vinh Ha Dinh Thi, Olivier Coriton, Isabelle Le Clainche, Dominique Arnaud, Sean P Gordon, Gabriella Linc, Pilar Catalan, Robert Hasterok, John P Vogel, Joseph Jahier, Boulos Chalhoub
Brachypodium hybridum (2n = 30) is a natural allopolyploid with highly divergent sub-genomes derived from two extant diploid species, B. distachyon (2n = 10) and B. stacei (2n = 20) that differ in chromosome evolution and number. We created synthetic B. hybridum allotetraploids by hybridizing various lines of B. distachyon and B. stacei. The initial amphihaploid F1 interspecific hybrids were obtained at low frequencies when B. distachyon was used as the maternal parent (0.15% or 0.245% depending on the line used) and were sterile...
2016: PloS One
https://www.readbyqxmd.com/read/27924020/lincsnp-2-0-an-updated-database-for-linking-disease-associated-snps-to-human-long-non-coding-rnas-and-their-tfbss
#15
Shangwei Ning, Ming Yue, Peng Wang, Yue Liu, Hui Zhi, Yan Zhang, Jizhou Zhang, Yue Gao, Maoni Guo, Dianshuang Zhou, Xin Li, Xia Li
We describe LincSNP 2.0 (http://bioinfo.hrbmu.edu.cn/LincSNP), an updated database that is used specifically to store and annotate disease-associated single nucleotide polymorphisms (SNPs) in human long non-coding RNAs (lncRNAs) and their transcription factor binding sites (TFBSs). In LincSNP 2.0, we have updated the database with more data and several new features, including (i) expanding disease-associated SNPs in human lncRNAs; (ii) identifying disease-associated SNPs in lncRNA TFBSs; (iii) updating LD-SNPs from the 1000 Genomes Project; and (iv) collecting more experimentally supported SNP-lncRNA-disease associations...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27905489/the-mammalian-linc-complex-regulates-genome-transcriptional-responses-to-substrate-rigidity
#16
Samer G Alam, Qiao Zhang, Nripesh Prasad, Yuan Li, Srikar Chamala, Ram Kuchibhotla, Birendra Kc, Varun Aggarwal, Shristi Shrestha, Angela L Jones, Shawn E Levy, Kyle J Roux, Jeffrey A Nickerson, Tanmay P Lele
Mechanical integration of the nucleus with the extracellular matrix (ECM) is established by linkage between the cytoskeleton and the nucleus. This integration is hypothesized to mediate sensing of ECM rigidity, but parsing the function of nucleus-cytoskeleton linkage from other mechanisms has remained a central challenge. Here we took advantage of the fact that the LINC (linker of nucleoskeleton and cytoskeleton) complex is a known molecular linker of the nucleus to the cytoskeleton, and asked how it regulates the sensitivity of genome-wide transcription to substratum rigidity...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27889481/mitotic-nuclear-envelope-breakdown-and-spindle-nucleation-are-controlled-by-interphase-contacts-between-centromeres-and-the-nuclear-envelope
#17
Alfonso Fernández-Álvarez, Cécile Bez, Eileen T O'Toole, Mary Morphew, Julia Promisel Cooper
Faithful genome propagation requires coordination between nuclear envelope (NE) breakdown, spindle formation, and chromosomal events. The conserved linker of nucleoskeleton and cytoskeleton (LINC) complex connects fission yeast centromeres and the centrosome, across the NE, during interphase. During meiosis, LINC connects the centrosome with telomeres rather than centromeres. We previously showed that loss of telomere-LINC contacts compromises meiotic spindle formation. Here, we define the precise events regulated by telomere-LINC contacts and address the analogous possibility that centromeres regulate mitotic spindle formation...
December 5, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27872710/linc-ror-and-its-spliced-variants-2-and-4-are-significantly-up-regulated-in-esophageal-squamous-cell-carcinoma
#18
Reza Sahebi, Mahshid Malakootian, Baharak Balalaee, Alireza Shahryari, Masoud Khoshnia, Mohammad Reza Abbaszadegan, Abdolvahab Moradi, Seyed Javad Mowla
OBJECTIVES: Similar characteristics of molecular pathways between cellular reprogramming events and tumorigenesis have been accentuated in recent years. Reprogramming-related transcription factors, also known as Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC), are also well-known oncogenes promoting cancer initiation, progression, and cellular transformation into cancer stem cells. Long non-coding RNAs (lncRNAs) are a major class of RNA molecules with emerging roles in stem cell pluripotency, cellular reprogramming, cellular transformation, and tumorigenesis...
October 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27871198/-it-is-easier-for-me-to-shoot-up-stigma-abandonment-and-why-hiv-positive-drug-users-in-russia-fail-to-link-to-hiv-care
#19
Tetiana Kiriazova, Karsten Lunze, Anita Raj, Natalia Bushara, Elena Blokhina, Evgeny Krupitsky, Carly Bridden, Dmitry Lioznov, Jeffrey H Samet, Allen L Gifford
Many HIV-positive people who inject drugs (PWID) globally are not receiving HIV care. This represents a major challenge among key populations to end the global HIV epidemic. This qualitative study explored the process and associated barriers of linking HIV-positive PWID who are in addiction treatment to HIV care in St. Petersburg, Russia. We conducted three focus groups and seven semi-structured interviews with participants in the LINC ("Linking Infectious and Narcology Care") project at addiction and HIV hospitals in St...
November 22, 2016: AIDS Care
https://www.readbyqxmd.com/read/27858498/sun1-splice-variants-sun1_888-sun1_785-and-predominant-sun1_916-variably-function-in-directional-cell-migration
#20
Yu Nishioka, Hiromasa Imaizumi, Junko Imada, Jun Katahira, Nariaki Matsuura, Miki Hieda
The LINC complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, such as nuclear migration, mechanotransduction and chromatin tethering in the meiotic phase. However, it remains unknown how these functions are regulated in different cell contexts. An inner nuclear membrane component of the LINC complex, SUN1, is ubiquitously expressed. The human SUN1 gene produces over 10 variants by alternative splicing. Although functions of SUN1 are relatively well characterized, functional differences among SUN1 splice variants are poorly characterized...
November 2016: Nucleus
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