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https://www.readbyqxmd.com/read/28647346/sting-is-involved-in-antiviral-immune-response-against-vzv-infection-via-the-induction-of-type-i-and-iii-ifn-pathways
#1
Ji-Ae Kim, Seul-Ki Park, Seong-Wook Seo, Chan-Hee Lee, Ok Sarah Shin
Varicella Zoster Virus (VZV) is a human-restricted α-herpesvirus that exhibits tropism for the skin. The VZV host receptors and downstream signaling pathways responsible for the antiviral innate immune response in the skin are not completely understood. Here, we show that stimulator of interferon genes (STING) mediates an important host defense against VZV infection in dermal cells including human dermal fibroblasts (HDFs) and HaCaT keratinocytes. Inhibition of STING using small interfering RNA (siRNA) or short hairpin RNA (shRNA)-mediated gene disruption resulted in enhanced viral replication but diminished IRF3 phosphorylation and induction of IFNs and pro-inflammatory cytokines...
June 21, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28646896/detection-of-the-plasmodium-falciparum-kelch-13-gene-p553l-mutation-in-sporozoites-isolated-from-mosquito-salivary-glands-in-south-central-vietnam
#2
Yoshimasa Maeno, Nguyen Tuyen Quang, Richard Culleton, Satoru Kawai, Gaku Masuda, Kaoru Hori, Shusuke Nakazawa, Ron P Marchand
BACKGROUND: Plasmodium falciparum has developed resistance against artemisinin in Southeast Asia. Mutations in the P. falciparum Kelch-13 (Pfk13) gene are associated with artemisinin resistance in vitro and in vivo. We investigated the prevalence of mutations in PfK13 from sporozoite-stage parasites isolated from the salivary glands of Anopheles dirus mosquitoes. METHODS: Mosquitoes were caught by human-landing catches at two locations within the Khanh Phu commune, South-Central Vietnam...
June 24, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28646161/circulating-exosomal-mir-125a-3p-as-a-novel-biomarker-for-early-stage-colon-cancer
#3
Jing Wang, Feihu Yan, Qi Zhao, Fei Zhan, Ruitao Wang, Liang Wang, Yanqiao Zhang, Xiaoyi Huang
Circulating exosome holds great potentials as biomarker for diagnosis and prognosis of human cancers. Previously, we have applied small RNA sequencing to identify aberrantly expressed exosomal miRNAs as candidates for diagnostic markers in colon cancer patients. In this validation cohort, plasma derived exosomal miRNA was isolated from 50 early-stage colon cancer patients and 50 matched healthy volunteers. Real-time qRT-PCR revealed that miR-125a-3p, miR-320c were significantly up-regulated in plasma exosomes of the patients with early stage colon cancer...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645154/alg-5-is-a-mirna-associated-argonaute-required-for-proper-developmental-timing-in-the-caenorhabditis-elegans-germline
#4
Kristen C Brown, Joshua M Svendsen, Rachel M Tucci, Brooke E Montgomery, Taiowa A Montgomery
Caenorhabditis elegans contains 25 Argonautes, of which, ALG-1 and ALG-2 are known to primarily interact with miRNAs. ALG-5 belongs to the AGO subfamily of Argonautes that includes ALG-1 and ALG-2, but its role in small RNA pathways is unknown. We analyzed by high-throughput sequencing the small RNAs associated with ALG-5, ALG-1 and ALG-2, as well as changes in mRNA expression in alg-5, alg-1 and alg-2 mutants. We show that ALG-5 defines a distinct branch of the miRNA pathway affecting the expression of genes involved in immunity, defense, and development...
June 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28643404/occurrence-of-late-relapse-of-hepatitis-c-virus-confirmed-by-molecular-analysis-after-sustained-virological-response-to-interferon-ribavirin-based-therapy
#5
Kazuhiko Hayashi, Masatoshi Ishigami, Satoshi Yasuda, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Tetsuya Ishikawa, Yoshiki Hirooka, Hidemi Goto
BACKGROUND AND AIM: The optimal duration of follow-up for patients who achieve sustained virological responses (SVR) has become an important issue. Reports on long-term follow-up of SVR have demonstrated that 99% of patients maintained SVR. However, the limitations of a majority of studies include small patient numbers, short study periods, and lack of molecular analysis of hepatitis C virus (HCV) genome. The present study sought to evaluate the late relapse rate in long-term follow-up of patients who achieved SVR, with molecular analysis of HCV...
June 22, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28642173/protein-functional-effector-sncrnas-pfernas-in-lung-cancer
#6
Malcolm Brock, Yuping Mei
PIWI-interacting RNA Likes (piR-Ls) were recently reported to regulate functions of their target phospho-Proteins (p-Proteins) in somatic lung cells. However, the mechanism underlying this functionality remains unclear. piR-Ls interact with their targets through direct binding but do not follow base-pairing rules, known to have important roles at levels of transcription, RNA processing and translation for small non-coding RNA (sncRNA). These observations imply a fundamentally different type of sncRNA with behavior that causes a molecular response in their target p-Proteins...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28641312/impact-of-novel-mir-145-3p-regulatory-networks-on-survival-in-patients-with-castration-resistant-prostate-cancer
#7
Yusuke Goto, Akira Kurozumi, Takayuki Arai, Nijiro Nohata, Satoko Kojima, Atsushi Okato, Mayuko Kato, Kazuto Yamazaki, Yasuo Ishida, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
BACKGROUND: Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed. METHODS: Next-generation sequencing revealed 945-1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC)...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28641106/antisense-oligonucleotides-translation-from-mouse-models-to-human-neurodegenerative-diseases
#8
REVIEW
Kathleen M Schoch, Timothy M Miller
Multiple neurodegenerative diseases are characterized by single-protein dysfunction and aggregation. Treatment strategies for these diseases have often targeted downstream pathways to ameliorate consequences of protein dysfunction; however, targeting the source of that dysfunction, the affected protein itself, seems most judicious to achieve a highly effective therapeutic outcome. Antisense oligonucleotides (ASOs) are small sequences of DNA able to target RNA transcripts, resulting in reduced or modified protein expression...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28640911/evolution-of-microrna-in-primates
#9
Jennifer C McCreight, Sean E Schneider, Damien B Wilburn, Willie J Swanson
MicroRNA play an important role in post-transcriptional regulation of most transcripts in the human genome, but their evolution across the primate lineage is largely uncharacterized. A particular miRNA can have one to thousands of messenger RNA targets, establishing the potential for a small change in sequence or overall miRNA structure to have profound phenotypic effects. However, the majority of non-human primate miRNA is predicted solely by homology to the human genome and lacks experimental validation. In the present study, we sequenced thirteen species representing a wide range of the primate phylogeny...
2017: PloS One
https://www.readbyqxmd.com/read/28640897/impact-of-selected-non-steroidal-anti-inflammatory-pharmaceuticals-on-microbial-community-assembly-and-activity-in-sequencing-batch-reactors
#10
Cong Jiang, Jinju Geng, Haidong Hu, Haijun Ma, Xingsheng Gao, Hongqiang Ren
This study covers three widely detected non-steroidal anti-inflammatory pharmaceuticals (NSAIDs), diclofenac (DCF), ibuprofen (IBP) and naproxen (NPX), as NSAIDs pollutants. The objective is to evaluate the impact of NSAIDs at their environmental concentrations on microbial community assembly and activity. The exposure experiments were conducted under three conditions (5 μg L-1 DCF, 5 μg L-1 DCF+5 μg L-1 IBP and 5 μg L-1 DCF+5 μg L-1 IBP+ 5 μg L-1 NPX) in sequencing batch reactors (SBRs) for 130 days...
2017: PloS One
https://www.readbyqxmd.com/read/28640690/a-new-layer-of-rrna-regulation-by-small-interference-rnas-and-the-nuclear-rnai-pathway
#11
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/28639203/development-of-therapeutic-dsp21-322-for-cancer-treatment
#12
Moo Rim Kang, Gongcheng Li, Tiejun Pan, Jin-Chun Xing, Long-Cheng Li
Small activating RNAs (saRNAs) are a class of artificially designed short duplex RNAs targeted at the promoter of a particular gene to upregulate its expression via a mechanism known as RNA activation (RNAa) and hold great promise for treating a wide variety of diseases including those undruggable by conventional therapies. The therapeutic benefits of saRNAs have been demonstrated in a number of preclinical studies carried out in different disease models including cancer. With many tumor suppressor genes (TSGs) downregulated due to either epigenetic mechanisms or haploinsufficiency resulting from deletion/mutation, cancer is an ideal disease space for saRNA therapeutics which can restore the expression of TSGs via epigenetic reprogramming...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28639199/treatment-of-pancreatic-cancer-by-aptamer-conjugated-c-ebp%C3%AE-sarna
#13
Sorah Yoon, John J Rossi
Pancreatic cancer is estimated to become the second-leading cause of cancer-related mortality by 2020. While the death rates of most other cancers continue to decline recently, the death rates of pancreatic cancer are still increasing, with less than 5% of patients achieving 5-year survival. Despite great efforts to improve treatment with combinational therapies in pancreatic cancer patients, limited progress has been made. V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) has been depicted as a therapeutic target in pancreatic cancer for many years...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28639190/target-recognition-mechanism-and-specificity-of-rna-activation
#14
Huiqing Cao, Xing Meng, Xiaoxia Wang, Zicai Liang
Small activating RNA (saRNA)-mediated gene activation has opened a new avenue for upregulating the expression of target genes by promoting endogenous transcription, a phenomenon known as RNA activation (RNAa). RNAa is distinct from the established RNAi mechanistic framework, although AGO2 is required by both. The precise mechanism of RNAa is currently disputable and has become a bottleneck in the development of this new technology. saRNA may achieve activation of target genes by directly binding to DNA targets in promoter, or interacting with antisense transcripts transcribed from overlapping promoter sequences, or by silencing other genes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28639188/small-rna-guided-transcriptional-gene-activation-rnaa-in-mammalian-cells
#15
Long-Cheng Li
Small RNA partnering with Argonaute (Ago) proteins plays important roles in diverse biological processes mainly by suppressing the expression of cognate target sequences. Mounting evidence reveals that the small RNA-Ago pathway can also positively regulate gene expression, a phenomenon termed as RNA activation (RNAa), which is evolutionarily conserved from Caenorhabditis elegans to human. In this chapter, I provide a general overview of mammalian RNAa phenomena and their basic characteristics and discuss recent advances toward understanding the nature of the molecular machinery responsible for RNAa and the development of RNAa-based research tools and therapeutics...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28637711/the-exon-junction-complex-and-srp54-contribute-to-drosophila-hedgehog-signaling-via-ci-rna-splicing
#16
Elisa Garcia Garcia, Jamie C Little, Daniel Kalderon
Hedgehog (Hh) regulates the Cubitus interruptus (Ci) transcription factor in Drosophila melanogaster by activating full-length Ci-155 and blocking processing to Ci-75 repressor. However, the interplay between regulation of Ci-155 levels and activity, as well as processing-independent mechanisms that affect Ci-155 levels have not been explored extensively. Here we identified Mago Nashi (Mago) and Y14 core Exon Junction Complex (EJC) proteins, as well as the Srp54 splicing factor as modifiers of Hh pathway activity under sensitized conditions...
June 21, 2017: Genetics
https://www.readbyqxmd.com/read/28636238/segmental-domain-selective-perdeuteration-and-small-angle-neutron-scattering-for-structural-analysis-of-multi-domain-proteins
#17
Miriam Sonntag, Pravin Jagtap, Bernd Simon, Marie-Sousai Appavou, Arie Geerlof, Ralf Stehle, Frank Gabel, Janosch Hennig, Michael Sattler
Multi-domain proteins play critical roles in fine-tuning essential processes in cellular signaling and gene regulation. Typically, multiple globular domains that are connected by flexible linkers undergo dynamic re-arrangements upon binding to protein, DNA or RNA ligands. RNA binding proteins (RBPs) represent an important class of multi-domain proteins, which regulate gene expression by recognizing linear or structured RNA sequence motifs. Here, we employ segmental perdeuteration of the three RNA recognition motif (RRM) domains in the RBP TIA-1 using Sortase A-mediated protein ligation...
June 21, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28635129/micrornas-involved-in-auxin-signalling-modulate-male-sterility-under-high-temperature-stress-in-cotton-gossypium-hirsutum
#18
Yuanhao Ding, Yizan Ma, Nian Liu, Jiao Xu, Qin Hu, Yaoyao Li, Yuanlong Wu, Sai Xie, Longfu Zhu, Ling Min, Xianlong Zhang
Male sterility caused by long-term high temperature (HT) stress occurs widely in crops. MicroRNAs (miRNAs), a class of endogenous non-coding small RNAs, play an important role in the plant response to various abiotic stresses. To dissect the working principle of miRNAs in male sterility under HT stress in cotton, a total of 112 known miRNAs, 270 novel miRNAs and 347 target genes were identified from anthers of HT-insensitive (84021) and HT-sensitive (H05) cotton cultivars under normal temperature (NT) and HT conditions through small RNA and degradome sequencing...
June 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28634372/dna-methylation-changes-in-endometrium-and-correlation-with-gene-expression-during-the-transition-from-pre-receptive-to-receptive-phase
#19
Viktorija Kukushkina, Vijayachitra Modhukur, Marina Suhorutšenko, Maire Peters, Reedik Mägi, Nilufer Rahmioglu, Agne Velthut-Meikas, Signe Altmäe, Francisco J Esteban, Jaak Vilo, Krina Zondervan, Andres Salumets, Triin Laisk-Podar
The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634236/alternative-evolutionary-pathways-for-drug-resistant-small-colony-variant-mutants-in-staphylococcus-aureus
#20
Sha Cao, Douglas L Huseby, Gerrit Brandis, Diarmaid Hughes
Staphylococcus aureus is known to generate small colony variants (SCVs) that are resistant to aminoglycoside antibiotics and can cause persistent and recurrent infections. The SCV phenotype is unstable, and compensatory mutations lead to restored growth, usually with loss of resistance. However, the evolution of improved growth, by mechanisms that avoid loss of antibiotic resistance, is very poorly understood. By selection with serial passaging, we isolated and characterized different classes of extragenic suppressor mutations that compensate for the slow growth of small colony variants...
June 20, 2017: MBio
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