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https://www.readbyqxmd.com/read/28340496/recent-developments-in-nanomedicine-for-melanoma-treatment
#1
REVIEW
Jian-Qin Tang, Xiao-Yang Hou, Chun-Sheng Yang, Ya-Xi Li, Yong Xin, Wen-Wen Guo, Zhi-Ping Wei, Yan-Qun Liu, Guan Jiang
Melanoma is a most aggressive skin cancer with limited therapeutic options and its incidence is increasing rapidly in recent years. The discovery and application of new targeted therapy agents have shown significant benefits. However, adverse side-effects and resistance to chemotherapy remain formidable challenges in the clinical treatment of malignant melanoma. Nanotherapeutics offers an important prospect of overcoming these drawbacks. The anti-tumoral applications of nanomedicine are varied, including those in chemotherapy, RNA interference, photothermal therapy, and photodynamic therapy...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340480/using-uhplc-q-trap-ms-as-a-complementary-technique-to-in-depth-mine-uplc-q-tof-ms-data-for-identifying-modified-nucleosides-in-urine
#2
Zhiwei Lu, Qing Wang, Meiling Wang, Shuang Fu, Qingqing Zhang, Zhixin Zhang, Huizhen Zhao, Yuehong Liu, Zhenhai Huang, Ziye Xie, Honghong Yu, Xiaoyan Gao
Modified nucleosides, metabolites of RNA, are potential biomarkers of cancer before the appearance of morphological abnormalities. It is of great significance to comprehensively detect and identify nucleosides in human urine for discovery of cancer biomarkers. However, the lower abundance, the greater polarity and the matrix effects make it difficult to detect urinary nucleosides. In this paper, an integrated method consisted of sample preparation followed by ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS) detection and primary identification, then ultra-high performance liquid chromatography coupled with hybrid triple quadrupole linear ion trap mass spectrometer (UHPLC Q-Trap/MS) further identification and validation were introduced...
March 12, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28340349/structure-reveals-mechanisms-of-viral-suppressors-that-intercept-a-crispr-rna-guided-surveillance-complex
#3
Saikat Chowdhury, Joshua Carter, MaryClare F Rollins, Sarah M Golden, Ryan N Jackson, Connor Hoffmann, Lyn'Al Nosaka, Joseph Bondy-Denomy, Karen L Maxwell, Alan R Davidson, Elizabeth R Fischer, Gabriel C Lander, Blake Wiedenheft
Genetic conflict between viruses and their hosts drives evolution and genetic innovation. Prokaryotes evolved CRISPR-mediated adaptive immune systems for protection from viral infection, and viruses have evolved diverse anti-CRISPR (Acr) proteins that subvert these immune systems. The adaptive immune system in Pseudomonas aeruginosa (type I-F) relies on a 350 kDa CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to bind foreign DNA and recruit a trans-acting nuclease for target degradation. Here, we report the cryo-electron microscopy (cryo-EM) structure of the Csy complex bound to two different Acr proteins, AcrF1 and AcrF2, at an average resolution of 3...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340337/structural-basis-of-rna-polymerase-i-transcription-initiation
#4
Christoph Engel, Tobias Gubbey, Simon Neyer, Sarah Sainsbury, Christiane Oberthuer, Carlo Baejen, Carrie Bernecky, Patrick Cramer
Transcription initiation at the ribosomal RNA promoter requires RNA polymerase (Pol) I and the initiation factors Rrn3 and core factor (CF). Here, we combine X-ray crystallography and cryo-electron microscopy (cryo-EM) to obtain a molecular model for basal Pol I initiation. The three-subunit CF binds upstream promoter DNA, docks to the Pol I-Rrn3 complex, and loads DNA into the expanded active center cleft of the polymerase. DNA unwinding between the Pol I protrusion and clamp domains enables cleft contraction, resulting in an active Pol I conformation and RNA synthesis...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340109/mth1-an-8-oxo-2-deoxyguanosine-triphosphatase-and-myh-a-dna-glycosylase-cooperate-to-inhibit-mutations-induced-by-chronic-exposure-to-oxidative-stress-of-ionising-radiation
#5
Sara Shakeri Manesh, Traimate Sangsuwan, Ali Pour Khavari, Asal Fotouhi, S Noushin Emami, Siamak Haghdoost
Our previous results showed that in addition to the immediate interaction of ionising radiation with DNA (direct and indirect effect), low-dose and chronic low-dose rate of irradiation induce endogenous oxidative stress. During oxidative stress, free radicals react with DNA, nucleoside triphosphates (dNTPs), proteins and lipids, and modify their structures. The MYH and MTH1 genes play important roles in preventing mutations induced by 8-hydroxy-guanine, which is an oxidised product of guanine. In this study, we used short-hairpin RNA to permanently knockdown MYH and MTH1 proteins in human lymphoblastoid TK6 cells...
March 16, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28339981/transcriptome-analysis-of-comb-and-testis-from-rose-comb-silky-chicken-r1-r1-and-beijing-fatty-wild-type-chicken-r-r
#6
Y Wang, J Li, C Feng, Y Zhao, X Hu, N Li
Rose-comb was one of the chicken comb-variants first used by Bateson and Punnet in 1902 to demonstrate Mendelian inheritance in animals. Rose-comb is a monogenic trait that has been widely described in chickens. It is caused by a large structural rearrangement that leads to mis-expression of transcription factor MNR2 on chromosome 7. Rose-comb has pleiotropic effects in homozygous roosters, which is associated with poor sperm mobility. It was postulated that this is caused by the disruption of the CCDC108 gene located at the distal inversion breakpoint...
March 2, 2017: Poultry Science
https://www.readbyqxmd.com/read/28339482/a-genome-wide-identification-and-analysis-of-the-dyw-deaminase-genes-in-the-pentatricopeptide-repeat-gene-family-in-cotton-gossypium-spp
#7
Bingbing Zhang, Guoyuan Liu, Xue Li, Liping Guo, Xuexian Zhang, Tingxiang Qi, Hailin Wang, Huini Tang, Xiuqin Qiao, Jinfa Zhang, Chaozhu Xing, Jianyong Wu
The RNA editing occurring in plant organellar genomes mainly involves the change of cytidine to uridine. This process involves a deamination reaction, with cytidine deaminase as the catalyst. Pentatricopeptide repeat (PPR) proteins with a C-terminal DYW domain are reportedly associated with cytidine deamination, similar to members of the deaminase superfamily. PPR genes are involved in many cellular functions and biological processes including fertility restoration to cytoplasmic male sterility (CMS) in plants...
2017: PloS One
https://www.readbyqxmd.com/read/28339459/functional-classification-of-dna-variants-by-hybrid-minigenes-identification-of-30-spliceogenic-variants-of-brca2-exons-17-and-18
#8
Eugenia Fraile-Bethencourt, Beatriz Díez-Gómez, Valeria Velásquez-Zapata, Alberto Acedo, David J Sanz, Eladio A Velasco
Mutation screening of the breast cancer genes BRCA1 and BRCA2 identifies a large fraction of variants of uncertain clinical significance (VUS) whose functional and clinical interpretations pose a challenge for genomic medicine. Likewise, an increasing amount of evidence indicates that genetic variants can have deleterious effects on pre-mRNA splicing. Our goal was to investigate the impact on splicing of a set of reported variants of BRCA2 exons 17 and 18 to assess their role in hereditary breast cancer and to identify critical regulatory elements that may constitute hotspots for spliceogenic variants...
March 24, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28335556/trm5-and-trmd-two-enzymes-from-distinct-origins-catalyze-the-identical-trna-modification-m%C3%A2-g37
#9
REVIEW
Sakurako Goto-Ito, Takuhiro Ito, Shigeyuki Yokoyama
The N¹-atom of guanosine at position 37 in transfer RNA (tRNA) is methylated by tRNA methyltransferase 5 (Trm5) in eukaryotes and archaea, and by tRNA methyltransferase D (TrmD) in bacteria. The resultant modified nucleotide m¹G37 positively regulates the aminoacylation of the tRNA, and simultaneously functions to prevent the +1 frameshift on the ribosome. Interestingly, Trm5 and TrmD have completely distinct origins, and therefore bear different tertiary folds. In this review, we describe the different strategies utilized by Trm5 and TrmD to recognize their substrate tRNAs, mainly based on their crystal structures complexed with substrate tRNAs...
March 21, 2017: Biomolecules
https://www.readbyqxmd.com/read/28335455/viral-protein-kinetics-of-piscine-orthoreovirus-infection-in-atlantic-salmon-blood-cells
#10
Hanne Merethe Haatveit, Øystein Wessel, Turhan Markussen, Morten Lund, Bernd Thiede, Ingvild Berg Nyman, Stine Braaen, Maria Krudtaa Dahle, Espen Rimstad
Piscine orthoreovirus (PRV) is ubiquitous in farmed Atlantic salmon (Salmo salar) and the cause of heart and skeletal muscle inflammation. Erythrocytes are important target cells for PRV. We have investigated the kinetics of PRV infection in salmon blood cells. The findings indicate that PRV causes an acute infection of blood cells lasting 1-2 weeks, before it subsides into persistence. A high production of viral proteins occurred initially in the acute phase which significantly correlated with antiviral gene transcription...
March 18, 2017: Viruses
https://www.readbyqxmd.com/read/28335389/characteristics%C3%A2-and%C3%A2-lethality%C3%A2-of%C3%A2-a%C3%A2-novel%C3%A2-recombinant%C3%A2-dermonecrotic%C3%A2-venom%C3%A2-phospholipase%C3%A2-d%C3%A2-from%C3%A2-hemiscorpius%C3%A2-lepturus
#11
Elham Torabi, Mahdi Behdani, Mohammad Hosseininejad Chafi, Reza Moazzami, Jean-Marc Sabatier, Vahid Khalaj, Delavar Shahbazzadeh, Kamran Pooshang Bagheri
Hemoscorpius lepturus is the most medically important scorpion in Iran. The clinical signs of H. lepturus envenomation are remarkably similar to those reported for brown spiders, including dermonecrosis, hematuria, renal failure and even death. The lethality and toxicity of brown spiders' venom have been attributed to its phospholipase D activity. This study aims to identify a phospholipase D with possible lethality and dermonecrotic activity in H. lepturus venom. In this study, a cDNA library of the venom glands was generated by Illumina RNA sequencing...
March 13, 2017: Toxins
https://www.readbyqxmd.com/read/28335026/melting-temperature-highlights-functionally-important-rna-structure-and-sequence-elements-in-yeast-mrna-coding-regions
#12
Fei Qi, Dmitrij Frishman
Secondary structure elements in the coding regions of mRNAs play an important role in gene expression and regulation, but distinguishing functional from non-functional structures remains challenging. Here we investigate the dependence of sequence-structure relationships in the coding regions on temperature based on the recent PARTE data by Wan et al. Our main finding is that the regions with high and low thermostability (high Tm and low Tm regions) are under evolutionary pressure to preserve RNA secondary structure and primary sequence, respectively...
March 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28335016/trna-derived-small-rnas-target-transposable-element-transcripts
#13
German Martinez, Sarah G Choudury, R Keith Slotkin
tRNA-derived RNA fragments (tRFs) are 18-26 nucleotide small RNAs that are not random degradation products, but are rather specifically cleaved from mature tRNA transcripts. Abundant in stressed or viral-infected cells, the function and potential targets of tRFs are not known. We identified that in the unstressed wild-type male gamete containing pollen of flowering plants, and analogous reproductive structure in non-flowering plant species, tRFs accumulate to high levels. In the reference plant Arabidopsis thaliana, tRFs are processed by Dicer-like 1 and incorporated into Argonaute1 (AGO1), akin to a microRNA...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28335001/fastkd1-and-fastkd4-have-opposite-effects-on-expression-of-specific-mitochondrial-rnas-depending-upon-their-endonuclease-like-rap-domain
#14
Erik Boehm, Sofia Zaganelli, Kinsey Maundrell, Alexis A Jourdain, Stéphane Thore, Jean-Claude Martinou
FASTK family proteins have been identified as regulators of mitochondrial RNA homeostasis linked to mitochondrial diseases, but much remains unknown about these proteins. We show that CRISPR-mediated disruption of FASTKD1 increases ND3 mRNA level, while disruption of FASTKD4 reduces the level of ND3 and of other mature mRNAs including ND5 and CYB, and causes accumulation of ND5-CYB precursor RNA. Disrupting both FASTKD1 and FASTKD4 in the same cell results in decreased ND3 mRNA similar to the effect of depleting FASTKD4 alone, indicating that FASTKD4 loss is epistatic...
March 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334976/a-sensitivity-analysis-of-rna-folding-nearest-neighbor-parameters-identifies-a-subset-of-free-energy-parameters-with-the-greatest-impact-on-rna-secondary-structure-prediction
#15
Jeffrey Zuber, Hongying Sun, Xiaoju Zhang, Iain McFadyen, David H Mathews
Nearest neighbor parameters for estimating the folding energy changes of RNA secondary structures are used in structure prediction and analysis. Despite their widespread application, a comprehensive analysis of the impact of each parameter on the precision of calculations had not been conducted. To identify the parameters with greatest impact, a sensitivity analysis was performed on the 291 parameters that compose the 2004 version of the free energy nearest neighbor rules. Perturbed parameter sets were generated by perturbing each parameter independently...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334903/n6-methyladenosine-alters-rna-structure-to-regulate-binding-of-a-low-complexity-protein
#16
Nian Liu, Katherine I Zhou, Marc Parisien, Qing Dai, Luda Diatchenko, Tao Pan
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and affects almost every stage of the mRNA life cycle. The YTH-domain proteins can specifically recognize m6A modification to control mRNA maturation, translation and decay. m6A can also alter RNA structures to affect RNA-protein interactions in cells. Here, we show that m6A increases the accessibility of its surrounding RNA sequence to bind heterogeneous nuclear ribonucleoprotein G (HNRNPG). Furthermore, HNRNPG binds m6A-methylated RNAs through its C-terminal low-complexity region, which self-assembles into large particles in vitro...
February 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334892/inhibition-of-homologous-phosphorolytic-ribonucleases-by-citrate-may-represent-an-evolutionarily-conserved-communicative-link-between-rna-degradation-and-central-metabolism
#17
Carlanne M Stone, Louise E Butt, Joshua C Bufton, Daniel C Lourenco, Darren M Gowers, Andrew R Pickford, Paul A Cox, Helen A Vincent, Anastasia J Callaghan
Ribonucleases play essential roles in all aspects of RNA metabolism, including the coordination of post-transcriptional gene regulation that allows organisms to respond to internal changes and environmental stimuli. However, as inherently destructive enzymes, their activity must be carefully controlled. Recent research exemplifies the repertoire of regulatory strategies employed by ribonucleases. The activity of the phosphorolytic exoribonuclease, polynucleotide phosphorylase (PNPase), has previously been shown to be modulated by the Krebs cycle metabolite citrate in Escherichia coli...
March 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334889/the-primary-transcriptome-of-neisseria-meningitidis-and-its-interaction-with-the-rna-chaperone-hfq
#18
Nadja Heidrich, Saskia Bauriedl, Lars Barquist, Lei Li, Christoph Schoen, Jörg Vogel
Neisseria meningitidis is a human commensal that can also cause life-threatening meningitis and septicemia. Despite growing evidence for RNA-based regulation in meningococci, their transcriptome structure and output of regulatory small RNAs (sRNAs) are incompletely understood. Using dRNA-seq, we have mapped at single-nucleotide resolution the primary transcriptome of N. meningitidis strain 8013. Annotation of 1625 transcriptional start sites defines transcription units for most protein-coding genes but also reveals a paucity of classical σ70-type promoters, suggesting the existence of activators that compensate for the lack of -35 consensus sequences in N...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334881/random-pseuoduridylation-in-vivo-reveals-critical-region-of-escherichia-coli-23s-rrna-for-ribosome-assembly
#19
Margus Leppik, Aivar Liiv, Jaanus Remme
Pseudouridine is the most common modified nucleoside in RNA, which is found in stable RNA species and in eukaryotic mRNAs. Functional analysis of pseudouridine is complicated by marginal effect of its absence. We demonstrate that excessive pseudouridines in rRNA inhibit ribosome assembly. Ten-fold increase of pseudouridines in the 16S and 23S rRNA made by a chimeric pseudouridine synthase leads to accumulation of the incompletely assembled large ribosome subunits. Hyper modified 23S rRNA is found in the r-protein assembly defective particles and are selected against in the 70S and polysome fractions showing modification interference...
March 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334877/iron-mediates-catalysis-of-nucleic-acid-processing-enzymes-support-for-fe-ii-as-a-cofactor-before-the-great-oxidation-event
#20
C Denise Okafor, Kathryn A Lanier, Anton S Petrov, Shreyas S Athavale, Jessica C Bowman, Nicholas V Hud, Loren Dean Williams
Life originated in an anoxic, Fe2+-rich environment. We hypothesize that on early Earth, Fe2+ was a ubiquitous cofactor for nucleic acids, with roles in RNA folding and catalysis as well as in processing of nucleic acids by protein enzymes. In this model, Mg2+ replaced Fe2+ as the primary cofactor for nucleic acids in parallel with known metal substitutions of metalloproteins, driven by the Great Oxidation Event. To test predictions of this model, we assay the ability of nucleic acid processing enzymes, including a DNA polymerase, an RNA polymerase and a DNA ligase, to use Fe2+ in place of Mg2+ as a cofactor during catalysis...
March 15, 2017: Nucleic Acids Research
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