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gene AND (therapy OR transfer)

Michelle M Leger, Laura Eme, Courtney W Stairs, Andrew J Roger
In a recent BioEssays paper [W. F. Martin, BioEssays 2017, 39, 1700115], William Martin sharply criticizes evolutionary interpretations that involve lateral gene transfer (LGT) into eukaryotic genomes. Most published examples of LGTs in eukaryotes, he suggests, are in fact contaminants, ancestral genes that have been lost from other extant lineages, or the result of artefactual phylogenetic inferences. Martin argues that, except for transfers that occurred from endosymbiotic organelles, eukaryote LGT is insignificant...
March 15, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Luca Palazzese, Marta Czernik, Domenico Iuso, Paola Toschi, Pasqualino Loi
Recently we have demonstrated the possibility to replace histones with protamine, through the heterologous expression of human protamine 1 (hPrm1) gene in sheep fibroblasts. Here we have optimized protaminization of somatic nucleus by adjusting the best concentration and exposure time to trichostatin A (TSA) in serum-starved fibroblasts (nuclear quiescence), before expressing Prm1 gene. To stop cell proliferation, we starved cells in 0.5% FBS in MEM ("starved"-ST group), whereas in the Control group (CTR) the cells were cultured in 10% FBS in MEM...
2018: PloS One
Vincent Plagnol, Samuel Woodhouse, Karen Howarth, Stefanie Lensing, Matt Smith, Michael Epstein, Mikidache Madi, Sarah Smalley, Catherine Leroy, Jonathan Hinton, Frank de Kievit, Esther Musgrave-Brown, Colin Herd, Katherine Baker-Neblett, Will Brennan, Peter Dimitrov, Nathan Campbell, Clive Morris, Nitzan Rosenfeld, James Clark, Davina Gale, Jamie Platt, John Calaway, Greg Jones, Tim Forshew
Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA...
2018: PloS One
Daniela Sorriento, Gaetano Santulli, Michele Ciccarelli, Angela Serena Maione, Maddalena Illario, Bruno Trimarco, Guido Iaccarino
We have recently demonstrated that the amino-terminal domain of G protein coupled receptor kinase (GRK) type 5, (GRK5-NT) inhibits NFκB activity in cardiac cells leading to a significant amelioration of LVH. Since GRK5-NT is known to bind calmodulin, this study aimed to evaluate the functional role of GRK5-NT in the regulation of calcium-calmodulin-dependent transcription factors. We found that the overexpression of GRK5-NT in cardiomyoblasts significantly reduced the activation and the nuclear translocation of NFAT and its cofactor GATA-4 in response to phenylephrine (PE)...
March 15, 2018: International Journal of Molecular Sciences
Maurizio Battaglia Parodi, Alessandro Arrigo, Robert E MacLaren, Emanuela Aragona, Lisa Toto, Rodolfo Mastropasqua, Maria Pia Manitto, Francesco Bandello
PURPOSE: Choroideremia is a rare degenerative retinal disease that causes incurable blindness. It occurs as a result of the deficiency of the X-linked CHM gene, which encodes the Rab escort protein 1 (REP1). Gene therapy has been developed to treat CHM using adeno-associated viral vectors and is currently undergoing clinical trials. Expression of the CHM gene is ubiquitous throughout the retina, and it is therefore important to identify which retinal layers are affected in the disease process...
March 14, 2018: Retina
Stephen S Curran, Eric E Pulis, Michael J Andres, Robin M Oversteet
Two cryptic species of haploporid digeneans belonging in Saccocoelioides are described from Costa Rica; one from a poeciliid fish Poecilia gillii and the other from a characid fish, Astyanx aeneus. Traditional morphological features are examined and found to be largely inefficient for differentiate among new species and 20 New World congeners. Comparison of ribosomal DNA sequences among the 2 new species, 2 North American, 4 Middle American, and 3 South American species of Saccocoelioides, including the type-species Saccocoelioides nanii from Argentina and Saccocoelioides sogandaresi from Texas, is effective for differentiating among these species...
March 16, 2018: Journal of Parasitology
Michael W Deem, Melia Elizabeth Bonomo
Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) constitute a multi-functional, constantly evolving immune system in bacteria and archaea cells. A heritable, molecular memory is generated of phage, plasmids, or other mobile genetic elements that attempt to attack the cell. This memory is used to recognize and interfere with subsequent invasions from the same genetic elements. This versatile prokaryotic tool has also been used to advance applications in biotechnology...
March 15, 2018: Physical Biology
Guillermo Montalban-Bravo, Courtney D DiNardo
Isocitrate dehydrogenases (IDHs) are enzymes involved in multiple metabolic and epigenetic cellular processes. Mutations in IDH1 or IDH2 are detected in approximately 20% of patients with acute myeloid leukemia (AML) and induce amino acid changes in conserved residues resulting in neomorphic enzymatic function and production of an oncometabolite, 2-hydroxyglutarate (R-2-HG). This leads to DNA hypermethylation, aberrant gene expression, cell proliferation and abnormal differentiation. IDH mutations diversely affect prognosis of patients with AML based on the location of the mutation and other co-occurring genomic abnormalities...
March 15, 2018: Future Oncology
Giacomo Reina, Ngoc Do Quyen Chau, Yuta Nishina, Alberto Bianco
Several studies have demonstrated the ability of graphene oxide (GO) to efficiently adsorb small-interfering RNA (siRNA) on its surface and to transport it into cells. However, studies on whether and how siRNA interacts with GO are still inconclusive. In this context, understanding the interaction between GO and siRNA is fundamental to design new efficient gene silencing tools. In this work, the interactions between GO and siRNA molecules were systematically investigated. We focused on how the GO size, oxygenated groups present on the surface and chemical functionalization affect the double helix siRNA structure, using gel electrophoresis, UV-Vis spectroscopy, fluorescence resonance energy transfer (FRET) and circular dichroism (CD)...
March 15, 2018: Nanoscale
Zachary Niday, Anastasios V Tzingounis
Exome and targeted sequencing have revolutionized clinical diagnosis. This has been particularly striking in epilepsy and neurodevelopmental disorders, for which new genes or new variants of preexisting candidate genes are being continuously identified at increasing rates every year. A surprising finding of these efforts is the recognition that gain of function potassium channel variants are actually associated with certain types of epilepsy, such as malignant migrating partial seizures of infancy or early-onset epileptic encephalopathy...
March 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Tingchao Mao, Chengquan Han, Ruizhi Deng, Biao Wei, Peng Meng, Yan Luo, Yong Zhang
Epigenetic modifications extensively occur in mammalian embryonic development and cell differentiation process. They play an essential role in the reprogramming of nuclei during somatic cell nuclear transfer (SCNT) and subsequent in vitro embryonic development. Recently, SCNT embryos have been verified to contain a subnormal level of histone H3K4 dimethylation (H3K4me2) in contrast to in vitro fertilized embryos. This finding suggested that increasing H3K4me2 levels may ameliorate the aberrant development of cloned embryos...
March 15, 2018: Systems Biology in Reproductive Medicine
Ming-Xing Zhang, Shan-Shan Hong, Qing-Qing Cai, Meng Zhang, Jun Chen, Xiao-Yan Zhang, Cong-Jian Xu
Ovarian cancer is the leading cause of cancer death among gynecological malignancies. The high mortality rate has not been significantly reduced despite advances in surgery and chemotherapy. Gene therapy shows therapeutic potential, but several key issues must be resolved before clinical application. To minimize toxicity in noncancerous tissues, tumor-specific ligands are conjugated to vectors to increase the selectivity of drug delivery. The expression pattern of follicle-stimulating hormone (FSH) receptor in normal and cancer tissues provides an opportunity for highly selective drug delivery in ovarian cancer...
November 2018: Drug Delivery
Rehan M Hussain, Ninel Z Gregori, Thomas A Ciulla, Byron L Lam
Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options. Areas covered: The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis-β-carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields...
March 15, 2018: Expert Opinion on Pharmacotherapy
Charles K Davis, Sreekala S Nampoothiri, G K Rajanikant
The constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential to PHD2, FIH, and pVHL was further verified by re-docking, molecular dynamics (MD) simulation and by Drug Affinity Responsive Target Stability (DARTS) assay...
March 14, 2018: Molecular Neurobiology
Kelly Kyker-Snowman, Bracha Erlanger Avigdor, Mansoor Nasim, Ashley Cimino-Mathews, Sarah J Wheelan, Pedram Argani, Ben Ho Park
BACKGROUND/PURPOSE: Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of human cancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. EXPERIMENTAL DESIGN/METHODS: Here, we present a case report of a patient's primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER negative...
March 15, 2018: Breast Cancer Research and Treatment
Marjan Nokhbehsaim, Svenja Memmert, Anna Damanaki, Shanika Nanayakkara, Xiaoyan Zhou, Andreas Jäger, James Deschner
OBJECTIVES: Periodontopathogens induce immunoinflammatory responses characterized by the release of inflammatory mediators, e.g., interleukin (IL)-1β, IL-6, and IL-8. Ghrelin (GHRL) is an appetite hormone which mediates its effect via the functional receptor GHS-R1a. This study was to examine the effect of an inflammatory insult on GHS-R1a in human periodontal cells. MATERIALS AND METHODS: Periodontal ligament (PDL) cells and gingival fibroblasts (HGFs) were exposed to IL-1β in the presence and absence of GHRL...
March 14, 2018: Clinical Oral Investigations
Tomohiro Hirose, Yuri Fukuma, Ayumu Takeshita, Keiichiro Nishida
BACKGROUND: The role of tumor necrosis factor (TNF) in the inflammatory response in rheumatoid arthritis (RA) is well established, whereas less is known about the role of TNF's close homolog, lymphotoxin alpha (LTα). FINDINGS: Increased levels of LTα are found in the serum and synovial tissue of patients with RA, and in vitro studies found that LTα-induced proliferation of RA fibroblast-like synoviocytes was at a similar level to TNF. These findings support the idea that anti-LTα treatment could be beneficial in patients with RA, but pateclizumab, an anti-LTα antibody, was not as efficacious as the anti-TNF agent adalimumab in reducing symptoms of RA in a head-to-head study, suggesting that anti-LTα therapies might not represent a valid alternative treatment option in patients with RA...
March 14, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Beatriz Silva Lima, Mafalda Ascensão Videira
Since the human genome decoding, understanding and identification of genetic disturbances behind many diseases, including cancer, are intensively increasing. Scientific and technological advances in this area trigger the search for therapeutic (curative) approaches targeting the correction of gene disturbances. Gene therapy medicinal products (GTMPs) emerge in this context, bringing new challenges for their characterization. Compared to small molecules, biodistribution is fundamental to identifying target organs and anticipating safety and efficacy, may be integrated into safety and pharmacology studies, and may eventually be anticipated based on specificities of vectors and constructs...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
Paul J Choi, Joe Iwanaga, R Shane Tubbs, Emre Yilmaz
Owing to its rarity, rhabdomyosarcoma of the head and neck (HNRMS) has seldom been discussed in the literature. As most of the data is based only on the retrospective experiences of tertiary healthcare centers, there are difficulties in formulating a standard treatment protocol. Moreover, the disease is poorly understood at its pathological, genetic, and molecular levels. For instance, 20% of all histological assessment is inaccurate; even an experienced pathologist can confuse rhabdomyosarcoma (RMS) with neuroblastoma, Ewing's sarcoma, and lymphoma...
January 9, 2018: Curēus
Muthu K Shanmugam, Frank Arfuso, Surendar Arumugam, Arunachalam Chinnathambi, Bian Jinsong, Sudha Warrier, Ling Zhi Wang, Alan Prem Kumar, Kwang Seok Ahn, Gautam Sethi, Manikandan Lakshmanan
Oncogenesis is a multistep process mediated by a variety of factors including epigenetic modifications. Global epigenetic post-translational modifications have been detected in almost all cancers types. Epigenetic changes appear briefly and do not involve permanent changes to the primary DNA sequence. These epigenetic modifications occur in key oncogenes, tumor suppressor genes, and transcription factors, leading to cancer initiation and progression. The most commonly observed epigenetic changes include DNA methylation, histone lysine methylation and demethylation, histone lysine acetylation and deacetylation...
February 16, 2018: Oncotarget
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