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https://www.readbyqxmd.com/read/28646091/stress-specific-p38-map-kinase-activation-is-sufficient-to-drive-egf-receptor-endocytosis-but-not-nuclear-translocation
#1
Alejandra Tomas, Sylwia Jones, Simon O Vaughan, Daniel Hochhauser, Clare E Futter
P38 MAP kinase-dependent EGF receptor (EGFR) endocytosis is induced by stress. Ligand and stresses like X-rays, reportedly promote nuclear traffic of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression and so did not represent nuclear EGFR...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28646090/cellular-functions-of-wasp-family-proteins-at-a-glance
#2
REVIEW
Olga Alekhina, Ezra Burstein, Daniel D Billadeau
Proteins of the Wiskott-Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28646043/an-efficient-flp-based-toolkit-for-spatiotemporal-control-of-gene-expression-in-caenorhabditis-elegans
#3
Celia María Muñoz-Jiménez, Cristina Ayuso, Agnieszka Dobrzynska, Antonio Torres, Patricia de la Cruz Ruiz, Peter Askjaer
Site-specific recombinases are potent tools to regulate gene expression. In particular, the Cre and FLP enzymes are widely used to either activate or inactivate genes in a precise spatiotemporal manner. Both recombinases work efficiently in the popular model organism Caenorhabditis elegans but their use in this nematode is still only sporadic. To increase the utility of the FLP system in C. elegans we have generated a series of single-copy transgenic strains that stably express an optimized version of FLP in specific tissues or by heat induction...
June 23, 2017: Genetics
https://www.readbyqxmd.com/read/28646039/monocyte-adhesion-migration-and-extracellular-matrix-breakdown-is-regulated-by-integrin-%C3%AE-v%C3%AE-3-in-mycobacterium-tuberculosis-infection
#4
Sara Brilha, Riccardo Wysoczanski, Ashley M Whittington, Jon S Friedland, Joanna C Porter
In tuberculosis (TB), the innate inflammatory immune response drives tissue destruction, morbidity, and mortality. Monocytes secrete matrix metalloproteinases (MMPs), which have key roles in local tissue destruction and cavitation. We hypothesized that integrin signaling might regulate monocyte MMP secretion in pulmonary TB during cell adhesion to the extracellular matrix (ECM). Adhesion to type I collagen and fibronectin by Mycobacterium tuberculosis-stimulated monocytes increased MMP-1 gene expression by 2...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645367/base-excision-repair-variants-in-cancer
#5
Carolyn G Marsden, Julie A Dragon, Susan S Wallace, Joann B Sweasy
Base excision repair (BER) is a key genome maintenance pathway that removes endogenously damaged DNA bases that arise in cells at very high levels on a daily basis. Failure to remove these damaged DNA bases leads to increased levels of mutagenesis and chromosomal instability, which have the potential to drive carcinogenesis. Next-generation sequencing of the germline and tumor genomes of thousands of individuals has uncovered many rare mutations in BER genes. Given that BER is critical for genome maintenance, it is important to determine whether BER genomic variants have functional phenotypes...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28643793/genomic-rearrangements-in-sporadic-lymphangioleiomyomatosis-an-evolving-genetic-story
#6
Stephen J Murphy, Simone B Terra, Faye R Harris, Aqsa Nasir, Jesse S Voss, James B Smadbeck, Sarah H Johnson, Vishnu Serla, Jay H Ryu, Eunhee S Yi, Benjamin R Kipp, George Vasmatzis, Eva M Carmona
Sporadic lymphangioleiomyomatosis is a progressive pulmonary cystic disease resulting from the infiltration of smooth muscle-like lymphangioleiomyomatosis cells into the lung. The migratory/metastasizing properties of the lymphangioleiomyomatosis cell together with the presence of somatic mutations, primarily in the tuberous sclerosis complex gene (TSC2), lead many to consider this a low-grade malignancy. As malignant tumors characteristically accumulate somatic structural variations, which have not been well studied in sporadic lymphangioleiomyomatosis, we utilized mate pair sequencing to define structural variations within laser capture microdissected enriched lymphangioleiomyomatosis cell populations from five sporadic lymphangioleiomyomatosis patients...
June 23, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28642803/transcriptomic-profiles-of-aging-in-na%C3%A3-ve-and-memory-cd4-cells-from-mice
#7
Jackson Taylor, Lindsay Reynolds, Li Hou, Kurt Lohman, Wei Cui, Stephen Kritchevsky, Charles McCall, Yongmei Liu
BACKGROUND: CD4+ T cells can be broadly divided into naïve and memory subsets, each of which are differentially impaired by the aging process. It is unclear if and how these differences are reflected at the transcriptomic level. We performed microarray profiling on RNA derived from naïve (CD44(low)) and memory (CD44(high)) CD4+ T cells derived from young (2-3 month) and old (28 month) mice, in order to better understand the mechanisms of age-related functional alterations in both subsets...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28642371/electrostatic-interactions-between-the-ctx-phage-minor-coat-protein-and-the-bacterial-host-receptor-tola-drives-the-pathogenic-conversion-of-vibrio-cholerae
#8
Laetitia Houot, Romain Navarro, Matthieu Nouailler, Denis Duché, Françoise Guerlesquin, Roland Lloubes
Vibrio cholerae is a natural inhabitant of aquatic environments and converts to a pathogen upon infection by a filamentous phage, CTXφ, that transmits the cholera toxin encoding genes. This toxigenic conversion of V. cholerae has evident implication in both genome plasticity and epidemic risk, but the early stages of the infection have not been thoroughly studied. CTXφ transit across the bacterial periplasm requires binding between the minor coat protein named pIII and a bacterial inner-membrane receptor, TolA, which is part of the conserved Tol-Pal molecular motor...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28642153/characterization-of-the-differential-coregulator-binding-signatures-of-the-retinoic-acid-receptor-subtypes-upon-ant-agonist-action
#9
Ignacio Miro Estruch, Diana Melchers, René Houtman, Laura H J de Haan, John P Groten, Jochem Louisse, Ivonne M C M Rietjens
Retinoic Acid Receptor alpha (RARα/NR1B1), Retinoic Acid Receptor beta (RARβ/NR1B2) and Retinoic Acid Receptor gamma (RARγ/NR1B3) are transcription factors regulating gene expression in response to retinoids. Within the RAR genomic pathways, binding of RARs to coregulators is a key intermediate regulatory phase. However, ligand-dependent interactions between the wide variety of coregulators that may be present in a cell and the different RAR subtypes are largely unknown. The aim of this study is to characterize the coregulator binding profiles of RARs in the presence of the pan-agonist all-trans-Retinoic Acid (AtRA); the subtype-selective agonists Am80 (RARα), CD2314 (RARβ) and BMS961 (RARγ); and the antagonist Ro415253...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641575/phylogenetic-and-paleobotanical-evidence-for-late-miocene-diversification-of-the-tertiary-subtropical-lineage-of-ivies-hedera-l-araliaceae
#10
V Valcárcel, B Guzmán, N G Medina, P Vargas, J Wen
BACKGROUND: Hedera (ivies) is one of the few temperate genera of the primarily tropical Asian Palmate group of the Araliaceae, which extends its range out of Asia to Europe and the Mediterranean basin. Phylogenetic and phylogeographic results suggested Asia as the center of origin and the western Mediterranean region as one of the secondary centers of diversification. The bird-dispersed fleshy fruits of ivies suggest frequent dispersal over long distances (e.g. Macaronesian archipelagos), although reducing the impact of geographic barriers to gene flow in mainland species...
June 22, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28641076/elevated-cd26-expression-by-skin-fibroblasts-distinguishes-a-profibrotic-phenotype-involved-in-scar-formation-compared-to-gingival-fibroblasts
#11
Wesley Mah, Guoqiao Jiang, Dylan Olver, Corrie Gallant-Behm, Colin Wiebe, David A Hart, Leeni Koivisto, Hannu Larjava, Lari Häkkinen
Compared to skin, wound healing in oral mucosa is faster and produces less scarring, but the mechanisms involved are incompletely understood. Studies in mice have linked high expression of CD26 to a profibrotic fibroblast phenotype, but this has not been tested in models more relevant for humans. We hypothesized that CD26 is highly expressed by human skin fibroblasts (SFBLs), and this associates with a profibrotic phenotype distinct from gingival fibroblasts (GFBLs). We compared CD26 expression in human gingiva and skin and in gingival and hypertrophic-like scar-forming skin wound healing in a pig model, and used three-dimensional cultures of human GFBLs and SFBLs...
June 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28640877/identification-of-c-ebp%C3%AE-as-a-novel-target-of-the-hpv8-e6-protein-regulating-mir-203-in-human-keratinocytes
#12
Anna M Marthaler, Marta Podgorska, Pascal Feld, Alina Fingerle, Katrin Knerr-Rupp, Friedrich Grässer, Hans Smola, Klaus Roemer, Elke Ebert, Yoo-Jin Kim, Rainer M Bohle, Cornelia S L Müller, Jörg Reichrath, Thomas Vogt, Magdalena Malejczyk, Sławomir Majewski, Sigrun Smola
Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet. In this study we demonstrate that microRNA-203 (miR-203), a key regulator of epidermal proliferation and differentiation, is strongly down-regulated in HPV8-positive EV-lesions...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640690/a-new-layer-of-rrna-regulation-by-small-interference-rnas-and-the-nuclear-rnai-pathway
#13
Xufei Zhou, Xiangyang Chen, Yun Wang, Xuezhu Feng, Shouhong Guang
Ribosome biogenesis drives cell growth and proliferation, but mechanisms that modulate this process remain poorly understood. For a long time, small ribosomal RNA sequences have been widely treated as non-specific degradation products and neglected as garbage sequences. Recently, we identified a new class of antisense ribosomal siRNAs (risiRNAs) that downregulate pre-rRNA through the nuclear RNAi pathway in C. elegans. risiRNAs exhibit sequence characteristics similar to 22G RNA while complement to 18S and 26S rRNA...
June 22, 2017: RNA Biology
https://www.readbyqxmd.com/read/28639619/long-noncoding-rna-lnchifcar-mir31hg-is-a-hif-1%C3%AE-co-activator-driving-oral-cancer-progression
#14
Jing-Wen Shih, Wei-Fan Chiang, Alexander T H Wu, Ming-Heng Wu, Ling-Yu Wang, Yen-Ling Yu, Yu-Wen Hung, Wen-Chang Wang, Cheng-Ying Chu, Chiu-Lien Hung, Chun A Changou, Yun Yen, Hsing-Jien Kung
Long noncoding RNAs (lncRNAs) have been implicated in hypoxia/HIF-1-associated cancer progression through largely unknown mechanisms. Here we identify MIR31HG as a hypoxia-inducible lncRNA and therefore we name it LncHIFCAR (long noncoding HIF-1α co-activating RNA); we describe its oncogenic role as a HIF-1α co-activator that regulates the HIF-1 transcriptional network, crucial for cancer development. Extensive analyses of clinical data indicate LncHIFCAR level is substantially upregulated in oral carcinoma, significantly associated with poor clinical outcomes and representing an independent prognostic predictor...
June 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28639100/sting-mediated-dna-sensing-in-cancer-immunotherapy
#15
REVIEW
Xiang Zhou, Zhengfan Jiang
While STING (STimulator of INterferon Genes) has been shown to be essential for cytosolic DNA-triggered innate immune activation, accumulated evidence obtained from various studies suggested that an intrinsic relevance of STING-associated signaling in tumorigenesis can be observed. Also, several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for STING, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents...
May 29, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28637688/fus-ddit3-fusion-protein-driven-igf-ir-signaling-is-a-therapeutic-target-in-myxoid-liposarcoma
#16
Marcel Trautmann, Jasmin Menzel, Christian Bertling, Magdalene Cyra, Ilka Isfort, Konrad Steinestel, Sandra Elges, Inga Grünewald, Bianca Altvater, Claudia Rossig, Stefan Fröhling, Susanne Hafner, Thomas Simmet, Pierre Åman, Eva Wardelmann, Sebastian Huss, Wolfgang Hartmann
Purpose: Myxoid liposarcoma is an aggressive disease with particular propensity to develop hematogenic metastases. Over 90% of myxoid liposarcoma are characterized by a reciprocal t(12;16)(q13;p11) translocation. The resulting chimeric FUS-DDIT3 fusion protein plays a crucial role in myxoid liposarcoma pathogenesis; however, its specific impact on oncogenic signaling pathways remains to be substantiated. We here investigate the functional role of FUS‑DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis...
June 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28637661/the-full-transforming-capacity-of-mll-af4-is-interlinked-with-lymphoid-lineage-commitment
#17
Shan Lin, Roger T Luo, Mahesh Shrestha, Michael J Thirman, James C Mulloy
Chromosome rearrangements involving mixed-lineage leukemia gene (MLL) create MLL-fusion proteins, which could drive both acute lymphoblastic and myeloid leukemia (ALL and AML). The lineage decision of MLL-fusion leukemia is influenced by the fusion partner and microenvironment. To investigate the interplay of fusion proteins and microenvironment in lineage choice, we transplanted human hematopoietic stem and progenitor cells (HSPC) expressing MLL-AF9 or MLL-Af4 into immunodeficient NSGS mice, which strongly promote myeloid development...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28637399/biomineralized-recombinant-collagen-based-scaffold-mimicking-native-bone-enhances-mesenchymal-stem-cell-interaction-and-differentiation
#18
Gloria Belén Ramirez-Rodríguez, Monica Montesi, Silvia Panseri, Simone Sprio, Anna Tampieri, Monica Sandri
The need of synthetic bone grafts that recreate from macro to nanoscale level the biochemical and biophysical cues of bone extracellular matrix (ECM) has been a major driving force for the development of new generation of biomaterials. In this study, synthetic bone substitutes have been synthesized via biomimetic mineralization of a recombinant collagen type I derived peptide (RCP), enriched in tri-amino acid sequence arginine-glycine-aspartate (RGD). 3D isotropic porous scaffolds of three different compositions are developed by freeze-drying: non-mineralized (RCP, as a control), mineralized (Ap/RCP) and mineralized scaffolds in presence of magnesium (MgAp/RCP) that closely imitate bone composition...
June 22, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28636785/sperm-competition-suppresses-gene-drive-among-experimentally-evolving-populations-of-house-mice
#19
Andri Manser, Anna K Lindholm, Leigh W Simmons, Renée C Firman
Drive genes are genetic elements that manipulate the 50% ratio of Mendelian inheritance in their own favour, allowing them to rapidly propagate through populations. The action of drive genes is often hidden, making detection and identification inherently difficult. Yet drive genes can have profound evolutionary consequences for the populations that harbour them: most known drivers are detrimental to organismal gamete development, reproduction and survival. In this study, we identified the presence of a well-known drive gene called t haplotype post-hoc in eight replicate selection lines of house mice that had been evolving under enforced monandry or polyandry for 20 generations...
June 21, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#20
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
June 21, 2017: Nature
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