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Heqiang Sun, Hanmei Yuan, Ranjing Tan, Bin Li, Gang Guo, Jinyong Zhang, Haiming Jing, Yi Qin, Zhuo Zhao, Quanming Zou, Chao Wu
Helicobacter pylori has infected more than half of the world's population, causing gastritis, gastric ulcers, gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. The oral recombinant Helicobacter pylori vaccine currently used has made great progress in addressing this problem, however, its efficacy and longevity still need to be improved. Th1 and Th17 cells play essential roles in local protection against Helicobacter pylori in the stomach mucosa. Additionally, protective immunodominant antigens are the preferred for a vaccine...
February 23, 2018: Oncotarget
Ana Trapero, Angela Pacitto, Vinayak Singh, Mohamad Sabbah, Anthony G Coyne, Valerie Mizrahi, Tom L Blundell, David B Ascher, Chris Abell
Tuberculosis (TB) remains a major cause of mortality worldwide, and improved treatments are needed to combat emergence of drug resistance. Inosine 5´-monophosphate dehydrogenase (IMPDH), a crucial enzyme required for de novo synthesis of guanine nucleotides, is an attractive TB drug target. Herein, we describe the identification of potent IMPDH inhibitors using fragment-based screening and structure-based design techniques. Screening of a fragment library for Mycobacterium thermoresistible (Mth) IMPDH(ΔCBS) inhibitors identified a low affinity phenylimidazole derivative...
March 16, 2018: Journal of Medicinal Chemistry
Cheng-Han Yu, Chi-Chi Chou, Der-Yen Lee, Kay-Hooi Khoo, Geen-Dong Chang
Phenyl vinyl sulfone (PVS) and phenyl vinyl sulfonate (PVSN) inactivate protein tyrosine phosphatases (PTPs) by mimicking the phosphotyrosine structure and providing a Michael addition acceptor for the active-site cysteine residue of PTPs, thus forming covalent adducts between PVS (or PVSN) and PTPs. We developed a specific antiserum against PVS. This antiserum can be used in general antibody-based assays such as immunoblotting, immunofluorescence staining, and immunoprecipitation. Target identification through immunoprecipitation and mass spectrometry analysis reveals potential targets of PVS, mostly proteins with reactive cysteine residues or low-pKa cysteine residues that are prone to reversible redox modifications...
March 14, 2018: Bioscience Reports
Dicky Tri Utama, Seung Gyu Lee, Ki Ho Baek, Aera Jang, Jae In Pak, Sung Ki Lee
Objective: This study aimed to observe whether high-pressure processing (HPP) affected aroma development and the degradation rate of umami taste-related ATP breakdown products, specifically inosinic acid in grass-fed beef during vacuum aging. Methods: Strip loin (longissimus lumborum) cuts obtained from six grass-fed Friesian Holstein steers (32 months old) on day 4 post slaughter were vacuum-packed and subjected to pressurization at 300 and 500 MPa for 180 s at 15 ± 2°C...
March 13, 2018: Asian-Australasian Journal of Animal Sciences
Audrone Lapinaite, Jennifer A Doudna, Jamie H D Cate
Argonaute proteins (Agos) are present in all domains of life. Although the physiological function of eukaryotic Agos in regulating gene expression is well documented, the biological roles of many of their prokaryotic counterparts remain enigmatic. In some bacteria, Agos are associated with CRISPR (clustered regularly interspaced short palindromic repeats) loci and use noncanonical 5'-hydroxylated guide RNAs (gRNAs) for nucleic acid targeting. Here we show that using 5-bromo-2'-deoxyuridine (BrdU) as the 5' nucleotide of gRNAs stabilizes in vitro reconstituted CRISPR-associated Marinitoga piezophila Argonaute-gRNA complexes (MpAgo RNPs) and significantly improves their specificity and affinity for RNA targets...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Oscar Franzén, Raili Ermel, Katyayani Sukhavasi, Rajeev Jain, Anamika Jain, Christer Betsholtz, Chiara Giannarelli, Jason C Kovacic, Arno Ruusalepp, Josefin Skogsberg, Ke Hao, Eric E Schadt, Johan L M Björkegren
RNA editing modifies transcripts and may alter their regulation or function. In humans, the most common modification is adenosine to inosine (A-to-I). We examined the global characteristics of RNA editing in 4,301 human tissue samples. More than 1.6 million A-to-I edits were identified in 62% of all protein-coding transcripts. mRNA recoding was extremely rare; only 11 novel recoding sites were uncovered. Thirty single nucleotide polymorphisms from genome-wide association studies were associated with RNA editing; one that influences type 2 diabetes (rs2028299) was associated with editing in ARPIN ...
2018: PeerJ
Yuria Shinohara, Mitsutoshi Tsukimoto
Damaged tissues and cells release intracellular purine nucleotides, which serve as intercellular signaling factors. We previously showed that exogenously added adenine nucleotide (250 μM ATP) suppressed the activation of murine splenic T lymphocytes. Here, we examined the effects of other purine nucleotides/nucleosides on mouse T cell activation. First, we found that pretreatment of mouse spleen T cells with 250 μM GTP, GDP, GMP, guanosine, ITP, IDP, IMP or inosine significantly reduced the release of stimulus-inducible cytokine IL-2...
March 7, 2018: Biochemical and Biophysical Research Communications
Yueling Zhang, Guicai Gao, Ruihong Lin, Jude Juventus Aweya, Mengyuan Tao, Fan Wang
Although vertebrate immunity has been well studied for the past decades, invertebrate immunity was much less explored. One possible reason was that in vitro culture system was not well established. In this study, Litopenaeus vannamei was applied as an invertebrate study model. Primary culture conditions for L. vannamei hemocytes were optimized to get relatively quiescent state cells. LPS was used as an immune stimulator and the responses of primary cultured hemocytes were transcriptomically analyzed. Our results showed that around 1600 genes were upregulated and 800 genes were downregulated from LPS treated hemocytes...
March 5, 2018: Fish & Shellfish Immunology
Qing Zhang
RNA editing is a posttranscriptional modification process that alters the sequence of RNA molecules. RNA editing is related to many human diseases. However, the identification of RNA editing sites typically requires matched genomic sequence or multiple related expression data sets. Here we describe the GIREMI tool (genome-independent identification of RNA editing by mutual information; ) that is designed to accurately and sensitively predict adenosine-to-inosine editing from a single RNA-Seq data set...
2018: Methods in Molecular Biology
Hao Lian, Qin-Hua Wang, Chang-Bin Zhu, Jie Ma, Wei-Lin Jin
Technological and methodological advancements have recently revolutionized our understanding of widespread epitranscriptome including RNA modifications and editing. N6 -methyladenosine (m6 A) represents the most prevalent internal modification in mammalian RNAs. Adenosine to inosine (A-to-I) RNA editing is an important mechanism underlying RNA generation and protein diversity through the post-transcriptional modification of single nucleotides in RNA sequences. In this review, we attempt to summarize its functional importance in various fundamental bioprocesses of m6 A and A-to-I editing...
March 2018: Trends in Cancer
Li Liu, Yan Wen, Lei Zhang, Peng Xu, Xiao Liang, Yanan Du, Ping Li, Awen He, QianRui Fan, Jingcan Hao, Wenyu Wang, Xiong Guo, Hui Shen, Qing Tian, Feng Zhang, Hong-Wen Deng
Context: Osteoporosis is a metabolic bone disease. The impact of blood metabolites on the development of osteoporosis remains elusive now. Objective: To explore the relationship between blood metabolites and osteoporosis. Design and Methods: We used 2,286 unrelated Caucasian subjects as discovery samples and 3,143 unrelated Caucasian subjects from the Framingham heart study (FHS) as replication samples. Bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry...
March 1, 2018: Journal of Clinical Endocrinology and Metabolism
Shenglan Qi, Huida Guan, Gang Deng, Tao Yang, Xuemei Cheng, Wei Liu, Ping Liu, Changhong Wang
Adenosine deaminase (ADA), which is a key enzyme in the metabolism of purine nucleosides, plays important roles in diverse disorders, such as tuberculosis, diabetes, liver disorders, and cancer. Determination of the activities of ADA and its isoenzymes in body fluids has received considerable attention in the diagnosis and treatment of relative diseases. Ultraviolet spectroscopy with adenosine (AD) as a substrate is a classical approach for screening potential ADA inhibitors by measuring the decrease in substrate (AD) at 265 nm or increase in the product (inosine) at 248 nm...
February 22, 2018: Journal of Pharmaceutical and Biomedical Analysis
Zehong Wei, Huihui Zhou, Yanjiao Zhang, Qin Zhang, Wenbing Zhang, Kangsen Mai
A previous study showed that flesh quality of large yellow croaker (LYC) was improved by feeding dietary hydroxyproline (Hyp, 0·69 %). The aim of the present study was to explore the underlying mechanisms using transcriptomics and metabolomics analysis. The metabolomics analysis showed that muscle metabolite profiles could be clearly separated between the basal diet and Hyp supplementation diet. Metabolites including betaine, Hyp, lactate, glucose-6-phosphate, trimethylamine N-oxide, taurine, creatine, inosine monophosphate, histamine and serine made significant contribution to the separation...
February 2018: British Journal of Nutrition
Amy E Pasquinelli
Adenosine deaminases that act on RNA (ADARs) convert adenosines (A) to inosines (I) in stretches of dsRNA. The biological purpose of these editing events for the vast majority of ADAR substrates is largely unknown. In this issue of Genes & Development, Reich and colleagues (pp. 271-282) demonstrate that in Caenorhabditis elegans , A-to-I editing in double-stranded regions of protein-coding transcripts protects these RNAs from targeting by the RNAi pathway. Disruption of this safeguard through loss of ADAR activity coupled with enhanced RNAi results in developmental abnormalities and profound changes in gene expression that suggest aberrant induction of an antiviral response...
February 1, 2018: Genes & Development
Ujvala Deepthi Gadde, Sungtaek Oh, Hyun S Lillehoj, Erik P Lillehoj
Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet...
February 26, 2018: Scientific Reports
Joshua D Bryant, Shannon R Sweeney, Enrique Sentandreu, Minhye Shin, Helene Ipas, Blerta Xhemalce, Jessica Momb, Stefano Tiziani, Dean R Appling
One-carbon (1C) metabolism is a universal folate-dependent pathway essential for de novo purine and thymidylate synthesis, amino acid interconversion, universal methyl-donor production, and regeneration of redox cofactors. Homozygous deletion of the 1C pathway gene Mthfd1l encoding methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like, which catalyzes mitochondrial formate production from 10-formyltetrahydrofolate, results in 100% penetrant embryonic neural tube defects (NTDs), underscoring the central role of mitochondrially derived formate in embryonic development and providing a mechanistic link between folate and NTDs...
February 26, 2018: Journal of Biological Chemistry
Khatuna Gagnidze, Violeta Rayon-Estrada, Sheila Harroch, Karen Bulloch, F Nina Papavasiliou
The transfer of genomic information from DNA to mRNA to protein usually occurs with high fidelity, but can also be subverted by a programmed RNA sequence alteration termed 'RNA editing', involving deamination of adenosine to inosine (decoded as guanosine), or of cytosine to uracil. These sequence changes can lead to cellular heterogeneity by generating variable sets of transcripts within otherwise identical cells. Recent studies have demonstrated that editing is most prevalent in cells and tissues with high propensity for plasticity...
February 23, 2018: Trends in Molecular Medicine
Emmanuel Quansah, Victor Ruiz-Rodado, Martin Grootveld, Tyra S C Zetterström
Abnormalities in the cerebellar circuitry have been suggested to contribute to some of the symptoms associated with attention deficit hyperactivity disorder (ADHD). The psychostimulant methylphenidate (MPH) is the major drug for treating this condition. Here, the effects of acute (2.0 mg/kg and 5.0 mg/kg) and chronic (2.0 mg/kg, twice daily for 15 days) MPH treatments were investigated in adolescent (35-40 days old) rats on monoaminergic and metabolic markers in the cerebellum. Data acquired indicates that acute MPH treatment (2...
February 22, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
S John Calise, Bing Zheng, Tomoko Hasegawa, Minoru Satoh, Natasa Isailovic, Angela Ceribelli, Luis E C Andrade, Katherine Boylan, Ilaria Cavazzana, Marvin J Fritzler, Ignacio Garcia de la Torre, Falk Hiepe, Kathryn Kohl, Carlo Selmi, Yehuda Shoenfeld, Angela Tincani, Edward K L Chan
BACKGROUND: Anti-mitochondrial antibodies (AMA) are found in >90% of primary biliary cholangitis patients. Anti-rods/rings antibodies (anti-RR) are most commonly associated with interferon-α and ribavirin treatment in hepatitis C patients. Clinical laboratories routinely screen for AMA and anti-RR using indirect immunofluorescence on HEp-2 cells (HEp-2-IFA). Therefore, we sought to establish reference materials for use in AMA and anti-RR testing. METHODS: AMA-positive and anti-RR-positive human plasma samples (AMA-REF and RR-REF), identified as potential reference materials based on preliminary data, were further validated by multiple laboratories using HEp-2-IFA, immunoprecipitation (IP), western blotting, IP-western, line immunoassay (LIA), addressable laser bead immunoassay (ALBIA) and enzyme-linked immunosorbent assay (ELISA)...
February 26, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
Concetta Panebianco, Kaarel Adamberg, Madis Jaagura, Massimiliano Copetti, Andrea Fontana, Signe Adamberg, Kaia Kolk, Raivo Vilu, Angelo Andriulli, Valerio Pazienza
BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-related death. We aimed to evaluate whether gemcitabine treatment shapes the gut microbiota in a model of PDAC xenografted mice. MATERIALS AND METHODS: Pancreatic cancer xenograft mice were subjected to gemcitabine injection once per week for 3 weeks to assess the tumor volume as compared to control mice injected with normal saline solution. The composition of fecal microbiota, the activation of NF-kB pathway in cancer tissues and the serum metabolomics were further analyzed...
February 22, 2018: Cancer Chemotherapy and Pharmacology
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