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https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#1
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
May 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28526984/reduced-weed-seed-shattering-by-silencing-a-cultivated-rice-gene-strategic-mitigation-for-escaped-transgenes
#2
Huanxin Yan, Lei Li, Ping Liu, Xiaoqi Jiang, Lei Wang, Jia Fang, Zhimin Lin, Feng Wang, Jun Su, Bao-Rong Lu
Transgene flow form a genetically engineered (GE) crop to its wild relatives may result in unwanted environmental consequences. Mitigating transgenes via introducing a gene that is disadvantageous to wild relatives but beneficial to crops, and is tightly-linked with the target transgenes, may provide a promising solution to limit the spread of transgenes in wild/weedy populations. Here we demonstrate a novel system with significantly reduced seed shattering in crop-weed hybrid descendants by partially silenced expression of the seed-shattering gene SH4 in cultivated rice, using artificial microRNA and antisense RNA techniques...
May 19, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28526032/multiplex-dnase-free-one-step-reverse-transcription-pcr-for-plasmodium-18s-rrna-and-spliced-gametocyte-specific-mrnas
#3
Amelia E Hanron, Zachary P Billman, Annette M Seilie, Tayla M Olsen, Matthew Fishbaugher, Ming Chang, Thomas Rueckle, Nicole Andenmatten, Bryan Greenhouse, Emmanuel Arinaitwe, John Rek, Smita Das, Gonzalo J Domingo, Kelly Shipman, Stefan H Kappe, James G Kublin, Sean C Murphy
BACKGROUND: Plasmodium gametocytes are sexual stages transmitted to female Anopheles mosquitoes. While Plasmodium parasites can be differentiated microscopically on Giemsa-stained blood smears, molecular methods are increasingly used because of their increased sensitivity. Molecular detection of gametocytes requires methods that discriminate between asexual and sexual stage parasites. Commonly tested gametocyte-specific mRNAs are pfs25 and pfs230 detected by reverse transcription polymerase chain reaction (RT-PCR)...
May 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28525572/crosstalk-between-vertical-and-horizontal-gene-transfer-plasmid-replication-control-by-a-conjugative-relaxase
#4
Fabián Lorenzo-Díaz, Cris Fernández-López, Rudi Lurz, Alicia Bravo, Manuel Espinosa
Horizontal gene transfer is a key process in the evolution of bacteria and also represents a source of genetic variation in eukaryotes. Among elements participating in gene transfer, thousands of small (<10 kb) mobile bacterial plasmids that replicate by the rolling circle mechanism represent a driving force in the spread of antibiotic resistances. In general, these plasmids are built as genetic modules that encode a replicase, an antibiotic-resistance determinant, and a relaxase that participates in their conjugative mobilization...
May 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28524599/modulation-of-nuclear-rest-by-alternative-splicing-a-potential-therapeutic-target-for-huntington-s-disease
#5
Guo-Lin Chen, Qi Ma, Dharmendra Goswami, Jianyu Shang, Gregory M Miller
Huntington's disease (HD) is caused by a genetically mutated huntingtin (mHtt) protein with expanded polyQ stretch, which impairs cytosolic sequestration of the repressor element-1 silencing transcription factor (REST), resulting in excessive nuclear REST and subsequent repression of neuronal genes. We recently demonstrated that REST undergoes extensive, context-dependent alternative splicing, of which exon-3 skipping (∆E3 )-a common event in human and nonhuman primates-causes loss of a motif critical for REST nuclear targeting...
May 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28524214/-possible-treatments-for-infantile-spinal-atrophy
#6
S I Pascual-Pascual, M Garcia-Romero
The new treatments of spinal muscular atrophy (SMA) due by SMN1 gene deletions are reviewed. There are several ways to increase the protein SMN, its activity and persistence in the tissues. Neuroprotective drugs as olesoxime or riluzole, and drugs acting by epigenetic mechanisms, as histone deacetylase inhibitors, have shown positive effects in preclinical studies but no clear efficacy in clinical trials. They might give in the future added benefits when used associated to other genetic modifying drugs. The best improvements in murine models of SMA and in clinical trials have been reached with antisense oligonucleotides, drugs that modify the splicing of SMN2, and they are expected to get better in the near future...
May 17, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28522613/dehydration-stress-extends-mrna-3-untranslated-regions-with-noncoding-rna-functions-in-arabidopsis
#7
Hai-Xi Sun, Yan Li, Qi-Wen Niu, Nam-Hai Chua
The 3' untranslated regions (3' UTRs) of mRNAs play important roles in the regulation of mRNA localization, translation and stability. Alternative cleavage and polyadenylation (APA) generates mRNAs with different 3' UTRs, but the involvement of this process in stress response has not yet been clarified. Here, we report that a subset of stress-related genes exhibits 3' UTR extensions of their mRNAs during dehydration stress. These extended 3' UTRs have characteristics of long noncoding RNAs and likely do not interact with miRNAs...
May 18, 2017: Genome Research
https://www.readbyqxmd.com/read/28522225/genetic-screening-of-spinal-muscular-atrophy-using-a-real-time-modified-cop-pcr-technique-with-dried-blood-spot-dna
#8
Mawaddah Ar Rochmah, Nur Imma Fatimah Harahap, Emma Tabe Eko Niba, Kenta Nakanishi, Hiroyuki Awano, Ichiro Morioka, Kazumoto Iijima, Toshio Saito, Kayoko Saito, Poh San Lai, Yasuhiro Takeshima, Atsuko Takeuchi, Yoshihiro Bouike, Maya Okamoto, Hisahide Nishio, Masakazu Shinohara
BACKGROUND: Spinal muscular atrophy (SMA) is a common neuromuscular disorder caused by mutations in SMN1. More than 95% of SMA patients carry homozygous SMN1 deletion. SMA is the leading genetic cause of infant death, and has been considered an incurable disease. However, a recent clinical trial with an antisense oligonucleotide drug has shown encouraging clinical efficacy. Thus, early and accurate detection of SMN1 deletion may improve prognosis of many infantile SMA patients. METHODS: A total of 88 DNA samples (37 SMA patients, 12 carriers and 39 controls) from dried blood spots (DBS) on filter paper were analyzed...
May 15, 2017: Brain & Development
https://www.readbyqxmd.com/read/28520401/identification-of-galnac-conjugated-antisense-oligonucleotide-metabolites-using-an-untargeted-and-generic-approach-based-on-high-resolution-mass-spectrometry
#9
Christophe Husser, Andreas Brink, Manfred Zell, Martina B Müller, Erich Koller, Simone Schadt
Antisense oligonucleotides linked by phosphorothioates are an important class of therapeutics under investigation in various pharmaceutical companies. Antisense oligonucleotides may be coupled to high-affinity ligands (triantennary N-acetyl ga-lactosamine = GalNAc) for hepatocyte-specific asialoglycoprotein receptors (ASGPR) to enhance uptake to hepatocytes and to increase potency. Since disposition and biotransformation of GalNAc-conjugated oligonucleotides is different from unconjugated oligonucleotides, appropriate analytical methods are required to identify main cleavage sites and degradation products of GalNAc conjugated and unconjugated oligonucleotides in target cells...
May 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28516330/why-antisense-could-make-sense-for-neurodegeneration
#10
T H Massey, N P Robertson
No abstract text is available yet for this article.
May 17, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28513871/potential-role-of-long-non-coding-rna-anril-in-pediatric-medulloblastoma-through-promotion-on-proliferation-and-migration-by-targeting-mir-323
#11
Hong Zhang, Xiuli Wang, Xinxin Chen
Medulloblastoma (MB) is a common primary tumor of the central nervous system diagnosed in pediatric patients. Survivors of MB are frequently accompanied by severe side effects, thus it is urgent to explore novel therapeutic target. First of all, the level of antisense non-coding RNA in the INK4 locus (ANRIL) in normal cerebellum and DAOY cells were evaluated. Then, the effect of ANRIL on DAOY cell proliferation, migration and apoptosis were tested. Then, qRT-PCR was performed to explore whether ANRIL acted as a sponge of miR-323...
May 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28513325/developmental-transitions-in-arabidopsis-are-regulated-by-antisense-rnas-resulting-from-bidirectionally-transcribed-genes
#12
Katarzyna Krzyczmonik, Agata Wroblewska-Swiniarska, Szymon Swiezewski
Transcription terminators are DNA elements located at the 3' end of genes that ensure efficient cleavage of nascent RNA generating the 3' end of mRNA, as well as facilitating disengagement of elongating DNA-dependent RNA polymerase II. Surprisingly, terminators are also a potent source of antisense transcription. We have recently described an Arabidopsis antisense transcript originating from the 3' end of a master regulator of Arabidopsis thaliana seed dormancy DOG1. In this review, we discuss the broader implications of our discovery in light of recent developments in yeast and Arabidopsis...
May 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28508101/in-depth-clinico-pathological-examination-of-rna-foci-in-a-large-cohort-of-c9orf72-expansion-carriers
#13
Mariely DeJesus-Hernandez, NiCole A Finch, Xue Wang, Tania F Gendron, Kevin F Bieniek, Michael G Heckman, Aliaksei Vasilevich, Melissa E Murray, Linda Rousseau, Rachael Weesner, Anthony Lucido, Meeia Parsons, Jeannie Chew, Keith A Josephs, Joseph E Parisi, David S Knopman, Ronald C Petersen, Bradley F Boeve, Neill R Graff-Radford, Jan de Boer, Yan W Asmann, Leonard Petrucelli, Kevin B Boylan, Dennis W Dickson, Marka van Blitterswijk, Rosa Rademakers
A growing body of evidence suggests that a loss of chromosome 9 open reading frame 72 (C9ORF72) expression, formation of dipeptide-repeat proteins, and generation of RNA foci contribute to disease pathogenesis in amyotrophic lateral sclerosis and frontotemporal dementia. Although the levels of C9ORF72 transcripts and dipeptide-repeat proteins have already been examined thoroughly, much remains unknown about the role of RNA foci in C9ORF72-linked diseases. As such, we performed a comprehensive RNA foci study in an extensive pathological cohort of C9ORF72 expansion carriers (n = 63)...
May 15, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28507919/hepatitis-c-virus-rna-strands-detection-in-peripheral-blood-mononuclear-cells-legitimizes-virus-eradication-in-negative-serum-pcr-na%C3%A3-ve-and-post-treatment-patients
#14
Mohamed Darwish Ahmed Abd Alla, Mostafa Kamel El Awady
Background and Aims: Hepatitis C virus (HCV) hepatotropism is associated with intra-peripheral blood mononuclear cell (PBMC) infection that causes post-treatment relapse in RNA seronegative patients. Our understanding of the association of non-viremic hepatic fibrosis with positive anti-HCV IgG antibodies and active hepatocellular damage might be increased by PBMCs screening for intracellular infection. Thus, the goals of this study included evaluation of PBMCs PCR for diagnosing HCV infection, addressing PBMCs plus serum real-time (SRT) PCR benefits over SRT-PCR alone, studying intra-PBMCs distribution of RNA sense and antisense strands, and identifying treatment feasibility in solitary intracellular infection...
March 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28507807/host-antitumor-resistance-improved-by-the-macrophage-polarization-in-a-chimera-model-of-patients-with-hcc
#15
Akira Asai, Yusuke Tsuchimoto, Hideko Ohama, Shinya Fukunishi, Yasuhiro Tsuda, Makiko Kobayashi, Kazuhide Higuchi, Fujio Suzuki
Despite major advances in curative and palliative approaches, hepatocellular carcinoma (HCC) is still the third leading cause of cancer-related death worldwide. M1 macrophages (Mϕ) play a key role in host antitumor defenses in HCC. In our study, CD14(+) cells were isolated from the peripheral blood of four groups of HCC patients (group-1, patients with stage 0 HCC; group-2, patients with stage A HCC; group-3, patients with stage B HCC; and group-4, patients with stage C HCC) and characterized phenotypically...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506463/rna-pol-ii-dynamics-modulate-co-transcriptional-chromatin-modification-ctd-phosphorylation-and-transcriptional-direction
#16
Nova Fong, Tassa Saldi, Ryan M Sheridan, Michael A Cortazar, David L Bentley
Eukaryotic genes are marked by conserved post-translational modifications on the RNA pol II C-terminal domain (CTD) and the chromatin template. How the 5'-3' profiles of these marks are established is poorly understood. Using pol II mutants in human cells, we found that slow transcription repositioned specific co-transcriptionally deposited chromatin modifications; histone H3 lysine 36 trimethyl (H3K36me3) shifted within genes toward 5' ends, and histone H3 lysine 4 dimethyl (H3K4me2) extended farther upstream of start sites...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28502783/evolution-expression-analysis-and-functional-verification-of-catharanthus-roseus-rlk1-like-kinase-crrlk1l-family-proteins-in-pear-pyrus-bretchneideri
#17
Xiaobing Kou, Kaijie Qi, Xin Qiao, Hao Yin, Xing Liu, Shaoling Zhang, Juyou Wu
The Catharanthus roseus RLK1-like kinase (CrRLK1L) family is involved in multiple processes during plant growth. However, little is known about CrRLK1L in the wood of the pear fruit tree Pyrus bretchneideri. In this study, 26 CrRLK1L gene members were identified in pear and were grouped into six subfamilies according to phylogenetic analyses. Evolutionary analysis indicated that recent whole genome duplication (WGD) and dispersed gene duplications may contribute to the expansion of the CrRLK1L gene family in pear...
May 10, 2017: Genomics
https://www.readbyqxmd.com/read/28502108/expression-of-the-filaggrin-gene-in-umbilical-cord-blood-predicts-eczema-risk-in-infancy-a-birth-cohort-study
#18
Ali H Ziyab, Susan Ewart, Gabrielle A Lockett, Hongmei Zhang, Hasan Arshad, John W Holloway, Wilfried Karmaus
BACKGROUND: Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking. OBJECTIVE: This study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy. METHODS: Infants enrolled in a birth cohort study (n = 94) were assessed for eczema at ages 3-, 6-, and 12-months...
May 14, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28499866/identification-and-characterization-of-novel-lncrnas-in-arabidopsis-thaliana
#19
Zhaogeng Lu, Xiao Xia, Bei Jiang, Kaibiao Ma, Likui Zhu, Li Wang, Biao Jin
Long noncoding RNAs (lncRNAs) are important regulators of various biological processes, but few studies have identified lncRNAs in plants; genome-wide discovery of novel lncRNAs is thus required. We used deep strand-specific sequencing (ssRNA-seq) to obtain approximately 62 million reads from all developmental stages of Arabidopsis thaliana and identified 156 novel lncRNAs that we classified according to their localization. These novel identified lncRNAs showed low expression levels and sequence conservation...
May 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28499244/microrna-24-1-suppresses-mouse-hepatoma-cell-invasion-and-metastasis-via-directly-targeting-o-glcnac-transferase
#20
Yubo Liu, Huang Huang, Meijun Liu, Qiong Wu, Wenli Li, Jianing Zhang
MicroRNAs (miRNAs) are endogenous non-coding regulatory RNAs involved in multiple cellular processes. Emerging evidences showed that miRNAs are involved in changing the cell surface glycosylation modification and oncogenesis. In this study, the role of miRNA-24-1 in O-GlcNAcylation and metastasis of mouse hepatocarcinoma cells was investigated. miRNAs expression array profiles were obtained from mouse hepatocarcinoma cell lines Hca-P and Hca-F with the low/high lymphatic metastasis potential, respectively. Based on the miRNAs expression array profiles, miRNA-24-1 expression was found to exhibit converse coincidence with metastasis potential, O-GlcNAc transferase (OGT) expression and O-GlcNAcylation...
May 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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