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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/28525572/crosstalk-between-vertical-and-horizontal-gene-transfer-plasmid-replication-control-by-a-conjugative-relaxase
#2
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
#3
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
#4
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/28508101/in-depth-clinico-pathological-examination-of-rna-foci-in-a-large-cohort-of-c9orf72-expansion-carriers
#5
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/28506463/rna-pol-ii-dynamics-modulate-co-transcriptional-chromatin-modification-ctd-phosphorylation-and-transcriptional-direction
#6
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
#7
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/28499244/microrna-24-1-suppresses-mouse-hepatoma-cell-invasion-and-metastasis-via-directly-targeting-o-glcnac-transferase
#8
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
https://www.readbyqxmd.com/read/28495973/contrasting-the-role-of-xct-and-glt-1-upregulation-in-the-ability-of-ceftriaxone-to-attenuate-the-cue-induced-reinstatement-of-cocaine-seeking-and-normalize-ampa-receptor-subunit-expression
#9
Amber L Lacrosse, Sinead M O'Donovan, Marian T Sepulveda-Orengo, Robert E McCullumsmith, Kathryn J Reissner, Marek Schwendt, Lori A Knackstedt
Chronic treatment with ceftriaxone attenuates reinstatement of cocaine-seeking while increasing the function of the glutamate transporter GLT-1 and system xC- (Sxc) in the nucleus accumbens core (NAc). Sxc contributes the majority of non-synaptic extracellular glutamate in the NAc, while GLT-1 is responsible for the majority of glutamate uptake. Here we used antisense to decrease the expression of GLT-1 and xCT (catalytic subunit of Sxc), in order to determine the relative importance of both proteins in mediating ceftriaxone's ability to prevent cue-induced reinstatement of cocaine-seeking and normalize glutamatergic proteins in the NAc of rats...
May 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28492351/mest-a-unique-epoxide-hydrolase-is-essential-for-optimal-growth-of-mycobacterium-tuberculosis-in-the-presence-of-styrene-oxide
#10
Manisha Chownk, Aashish Sharma, Kashmir Singh, Jagdeep Kaur
AIM: mesT of Mycobacterium tuberculosis, a hypothetical/putative epoxide hydrolase, is predicted to convert toxic epoxides to the more water-soluble and less toxic diols. Detailed characterization of the protein was carried out. RESULTS: mesT demonstrated esterase as well as epoxide hydrolase activity. It was membrane bound and was upregulated under hypoxic conditions. The enzyme was able to degrade styrene oxide. The presence of antisense against this gene resulted in the inhibition of in vitro bacterial growth/survival in the presence of styrene oxide...
May 11, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28491057/identification-of-genes-controlled-by-the-essential-yycfg-two-component-system-reveals-a-role-for-biofilm-modulation-in-staphylococcus-epidermidis
#11
Tao Xu, Yang Wu, Zhiwei Lin, Ralph Bertram, Friedrich Götz, Ying Zhang, Di Qu
Biofilms play a crucial role in the pathogenicity of Staphylococcus epidermidis, while little is known about whether the essential YycFG two-component signal transduction system (TCS) is involved in biofilm formation. We used antisense RNA (asRNA) to silence the yycFG TCS in order to study its regulatory functions in S. epidermidis. Strain 1457 expressing asRNA yycF exhibited a significant delay (~4-5 h) in entry to log phase, which was partially complemented by overexpressing ssaA. The expression of asRNA yycF and asRNA yycG resulted in a 68 and 50% decrease in biofilm formation at 6 h, respectively, while they had no significant inhibitory effect on 12 h biofilm formation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28487634/ryr2-mediated-ca-2-release-and-mitochondrial-ros-generation-partake-in-the-synaptic-dysfunction-caused-by-amyloid-%C3%AE-peptide-oligomers
#12
Carol D SanMartín, Pablo Veloso, Tatiana Adasme, Pedro Lobos, Barbara Bruna, Jose Galaz, Alejandra García, Steffen Hartel, Cecilia Hidalgo, Andrea C Paula-Lima
Amyloid β peptide oligomers (AβOs), toxic aggregates with pivotal roles in Alzheimer's disease, trigger persistent and low magnitude Ca(2+) signals in neurons. We reported previously that these Ca(2+) signals, which arise from Ca(2+) entry and subsequent amplification by Ca(2+) release through ryanodine receptor (RyR) channels, promote mitochondrial network fragmentation and reduce RyR2 expression. Here, we examined if AβOs, by inducing redox sensitive RyR-mediated Ca(2+) release, stimulate mitochondrial Ca(2+)-uptake, ROS generation and mitochondrial fragmentation, and also investigated the effects of the antioxidant N-acetyl cysteine (NAC) and the mitochondrial antioxidant EUK-134 on AβOs-induced mitochondrial dysfunction...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28485722/how-the-discovery-of-iss-n1-led-to-the-first-medical-therapy-for-spinal-muscular-atrophy
#13
REVIEW
N N Singh, M D Howell, E J Androphy, R N Singh
Spinal muscular atrophy (SMA), a prominent genetic disease of infant mortality, is caused by low levels of survival motor neuron (SMN) protein owing to deletions or mutations of the SMN1 gene. SMN2, a nearly identical copy of SMN1 present in humans, cannot compensate for the loss of SMN1 due to predominant skipping of exon 7 during pre-mRNA splicing. With the recent FDA approval of nusinersen (Spinraza™), the potential for correction of SMN2 exon 7 splicing as a SMA therapy has been affirmed. Nusinersen is an antisense oligonucleotide that targets intronic splicing silencer N1 (ISS-N1) discovered in 2004 at the University of Massachusetts Medical School...
May 9, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28485104/microrna-181a-promotes-docetaxel-resistance-in-prostate-cancer-cells
#14
Cameron M Armstrong, Chengfei Liu, Wei Lou, Alan P Lombard, Christopher P Evans, Allen C Gao
BACKGROUND: Docetaxel is one of the primary drugs used for treating castration resistant prostate cancer (CRPC). Unfortunately, over time patients invariably develop resistance to docetaxel therapy and their disease will continue to progress. The mechanisms by which resistance develops are still incompletely understood. This study seeks to determine the involvement of miRNAs, specifically miR-181a, in docetaxel resistance in CRPC. METHODS: Real-time PCR was used to measure miR-181a expression in parental and docetaxel resistant C4-2B and DU145 cells (TaxR and DU145-DTXR)...
June 2017: Prostate
https://www.readbyqxmd.com/read/28476952/specific-rnp-capture-with-antisense-lna-dna-mixmers
#15
Birgit Maria Rogell, Bernd Fischer, Mandy Rettel, Jeroen Krijgsveld, Alfredo Castello, Matthias W Hentze
RNA-binding proteins (RBPs) play essential roles in RNA biology, responding to cellular and environmental stimuli to regulate gene expression. Important advances have helped to determine the (near) complete repertoires of cellular RBPs. However, identification of RBPs associated with specific transcripts remains a challenge. Here, we describe "specific ribonucleoprotein (RNP) capture", a versatile method for the determination of the proteins bound to specific transcripts in vitro and in cellular systems. Specific RNP capture employs UV irradiation to covalently stabilize protein-RNA interactions taking place at "zero distance"...
May 5, 2017: RNA
https://www.readbyqxmd.com/read/28472637/lipid-oligonucleotide-conjugates-improve-cellular-uptake-and-efficiency-of-tctp-antisense-in-castration-resistant-prostate-cancer
#16
Sara Karaki, Sebastien Benizri, Raquel Mejías, Virginie Baylot, Nicolas Branger, Tan Nguyen, Brune Vialet, Khalid Oumzil, Philippe Barthélémy, Palma Rocchi
Translationally controlled tumor protein (TCTP) has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. Therefore, TCTP is now recognized as a potential therapeutic target in several cancers including prostate, breast and lung cancers. We previously showed that TCTP is overexpressed in castration-resistant prostate cancer (CRPC), and it has been implicated resistance to treatment. Recently, we developed TCTP antisense oligonucleotides (ASOs) to inhibit TCTP expression...
May 1, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28472174/augmented-quantal-release-of-acetylcholine-at-the-vertebrate-neuromuscular-junction-following-tdp-43-depletion
#17
Stefania Dzieciolowska, Pierre Drapeau, Gary Alan Barclay Armstrong
TAR DNA binding protein (TDP-43) is a 43 kD, predominately nuclear, protein involved in RNA metabolism. Of clinical significance is that the majority of amyotrophic lateral sclerosis (ALS) patients display abnormal accumulation of misfolded TDP-43 in the cytoplasm, which is coincident with a loss of nuclear localization in the afflicted regions of the central nervous system. Little is known about defects that arise in loss-of-function models, in particular synaptic defects that arise at the neuromuscular junction (NMJ)...
2017: PloS One
https://www.readbyqxmd.com/read/28471495/prognostic-implication-and-functional-role-of-long-noncoding-rna-igf2as-in-human-non-small-cell-lung-cancer
#18
Xin Zhang, Xiujuan Zhang, Rongpeng Hu, Lanxiang Hao
PURPOSE: Emerging evidence shows that long noncoding RNAs (lncRNAs) play important roles in human cancer. In this work, we examined the expression, prognostic implication and functional mechanisms of a lncRNA, insulin growth factor 2 antisense (IGF2AS) in non-small cell lung cancer (NSCLC). METHODS: IGF2AS gene expression was examined by qPCR in both in situ NSCLC clinical samples and in vitro NSCLC cell lines. In patients with NSCLC, postoperative overall survival was estimated according to endogenous IGF2AS expression in their cancerous lung tissues...
May 4, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28468311/tubacin-an-hdac6-selective-inhibitor-reduces-the-replication-of-the-japanese-encephalitis-virus-via-the-decrease-of-viral-rna-synthesis
#19
Chien-Yi Lu, Yi-Chih Chang, Chun-Hung Hua, Chieh Chuang, Su-Hua Huang, Szu-Hao Kung, Mann-Jen Hour, Cheng-Wen Lin
Japanese encephalitis virus (JEV), a neurotropic flavivirus, annually causes over 30,000 Japanese Encephalitis (JE) cases in East and Southeast Asia. Histone deacetylases (HDACs) modulate lysine acetylation of histones and non-histone proteins, regulating many processes including inflammation and antiviral immune response. This study investigated antiviral activity of pan- and selective-HDAC inhibitors as host-targeting agents against JEV. Among HDAC inhibitors, selective HDAC6 inhibitors (tubastatin-A (TBSA) and tubacin) concentration-dependently inhibited JEV-induced cytopathic effect and apoptosis, as well as reduced virus yield in human cerebellar medulloblastoma cells...
May 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28464849/transcriptome-analysis-of-smut-fungi-reveals-widespread-intergenic-transcription-and-conserved-antisense-transcript-expression
#20
Michael E Donaldson, Lauren A Ostrowski, Kristi M Goulet, Barry J Saville
BACKGROUND: Biotrophic fungal plant pathogens cause billions of dollars in losses to North American crops annually. The model for functional investigation of these fungi is Ustilago maydis. Its 20.5 Mb annotated genome sequence has been an excellent resource for investigating biotrophic plant pathogenesis. Expressed-sequence tag libraries and microarray hybridizations have provided insight regarding the type of transcripts produced by U. maydis but these analyses were not comprehensive and there were insufficient data for transcriptome comparison to other smut fungi...
May 2, 2017: BMC Genomics
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