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https://www.readbyqxmd.com/read/29353409/16s-rrna-gene-sequencing-reveals-altered-composition-of-gut-microbiota-in-individuals-with-kidney-stones
#1
Ruiqiang Tang, Yonghua Jiang, Aihua Tan, Juan Ye, Xiaoying Xian, Yuanliang Xie, Qiuyan Wang, Ziting Yao, Zengnan Mo
Nephrolithiasis is a common urological disease with high prevalence and recurrence rates. Characterizing gut microbiome profiles of nephrolithiasis patients may provide valuable insights and potential biomarkers for the disease. Therefore, we explored the relation between gut microbiome and nephrolithiasis using 16S ribosomal RNA (rRNA) gene sequencing. 13 patients with multiple kidney stones and 13 matched healthy controls were recruited. A decreasing trend in number of observed species in nephrolithiasis patients was detected, although statistical significance was not reached (p = 0...
January 20, 2018: Urolithiasis
https://www.readbyqxmd.com/read/29353086/ruthenium-dendrimers-as-carriers-for-anticancer-sirna
#2
Sylwia Michlewska, Maksim Ionov, Marta Maroto-Díaz, Aleksandra Szwed, Aliaksei Ihnatsyeu-Kachan, Svetlana Loznikova, Dzmitry Shcharbin, Marek Maly, Rafael Gomez Ramirez, Francisco Javier de la Mata, Maria Bryszewska
Dendrimers, which are considered as one of the most promising tools in the field of nanobiotechnology due to their structural organization, showed a great potential in gene therapy, drug delivery, medical imaging and as antimicrobial and antiviral agents. This article is devoted to study interactions between new carbosilane-based metallodendrimers containing ruthenium and anti-cancer small interfering RNA (siRNA). Formation of complexes between anti-cancer siRNAs and Ru-based carbosilane dendrimers was evaluated by transmission electron microscopy, circular dichroism and fluorescence...
January 12, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29352312/a-role-for-domain-i-of-the-hepatitis-c-virus-ns5a-protein-in-virus-assembly
#3
Chunhong Yin, Niluka Goonawardane, Hazel Stewart, Mark Harris
The NS5A protein of hepatitis C virus (HCV) plays roles in both virus genome replication and assembly. NS5A comprises three domains, of these domain I is believed to be involved exclusively in genome replication. In contrast, domains II and III are required for the production of infectious virus particles and are largely dispensable for genome replication. Domain I is highly conserved between HCV and related hepaciviruses, and is highly structured, exhibiting different dimeric conformations. To investigate the functions of domain I in more detail, we conducted a mutagenic study of 12 absolutely conserved and surface-exposed residues within the context of a JFH-1-derived sub-genomic replicon and infectious virus...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352121/efficient-differentiation-of-human-pluripotent-stem-cells-into-skeletal-muscle-cells-by-combining-rna-based-myod1-expression-and-pou5f1-silencing
#4
Tomohiko Akiyama, Saeko Sato, Nana Chikazawa-Nohtomi, Atsumi Soma, Hiromi Kimura, Shunichi Wakabayashi, Shigeru B H Ko, Minoru S H Ko
Direct generation of skeletal muscle cells from human pluripotent stem cells (hPSCs) would be beneficial for drug testing, drug discovery, and disease modelling in vitro. Here we show a rapid and robust method to induce myogenic differentiation of hPSCs by introducing mRNA encoding MYOD1 together with siRNA-mediated knockdown of POU5F1 (also known as OCT4 or OCT3/4). This integration-free approach generates functional skeletal myotubes with sarcomere-like structure and a fusion capacity in several days. The POU5F1 silencing facilitates MYOD1 recruitment to the target promoters, which results in the significant activation of myogenic genes in hPSCs...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352114/binding-of-nufip2-to-roquin-promotes-recognition-and-regulation-of-icos-mrna
#5
Nina Rehage, Elena Davydova, Christine Conrad, Gesine Behrens, Andreas Maiser, Jenny E Stehklein, Sven Brenner, Juliane Klein, Aicha Jeridi, Anne Hoffmann, Eunhae Lee, Umberto Dianzani, Rob Willemsen, Regina Feederle, Kristin Reiche, Jörg Hackermüller, Heinrich Leonhardt, Sonia Sharma, Dierk Niessing, Vigo Heissmeyer
The ubiquitously expressed RNA-binding proteins Roquin-1 and Roquin-2 are essential for appropriate immune cell function and postnatal survival of mice. Roquin proteins repress target mRNAs by recognizing secondary structures in their 3'-UTRs and by inducing mRNA decay. However, it is unknown if other cellular proteins contribute to target control. To identify cofactors of Roquin, we used RNA interference to screen ~1500 genes involved in RNA-binding or mRNA degradation, and identified NUFIP2 as a cofactor of Roquin-induced mRNA decay...
January 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29352088/an-archaeal-fluoride-responsive-riboswitch-provides-an-inducible-expression-system-for-hyperthermophiles
#6
Michael Clayton Speed, Brett W Burkhart, Jonathan W Picking, Thomas J Santangelo
Robust genetic systems for the hyperthermophilic Thermococcales have facilitated overexpression of native genes, allowed for the addition of sequences encoding secretion signals, epitope, and affinity tags to coding regions, and permitted the introduction of sequences encoding new proteins in these fast growing fermentative heterotrophs. Tightly controlled and easily manipulated systems permitting regulated gene expression are however limited for these hosts. Here we describe an alternative method for regulatory control reliant on a cis-encoded functional riboswitch in the model archaeon Thermococcus kodakarensis Despite the hyperthermophilic growth temperatures, the proposed structure of the riboswitch conforms to a fluoride-responsive riboswitch encoded in many bacteria, and similarly functions to regulate a component conserved fluoride export pathway...
January 19, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29351962/rna-helicases-in-rna-decay
#7
REVIEW
Vanessa Khemici, Patrick Linder
RNA molecules have the tendency to fold into complex structures or to associate with complementary RNAs that exoribonucleases have difficulties processing or degrading. Therefore, degradosomes in bacteria and organelles as well as exosomes in eukaryotes have teamed-up with RNA helicases. Whereas bacterial degradosomes are associated with RNA helicases from the DEAD-box family, the exosomes and mitochondrial degradosome use the help of Ski2-like and Suv3 RNA helicases.
January 19, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29351869/allosteric-kissing-complex-based-electrochemical-biosensor-for-sensitive-regenerative-and-versatile-detection-of-proteins
#8
Mingsha Zhao, Shanshan Zhang, Zhiqiang Chen, Changzhi Zhao, Li Wang, Shufeng Liu
Herein, an allosteric kissing complex-based electrochemical biosensor was ingeniously proposed for the simple, sensitive, regenerative and versatile detection of proteins. Two hairpins (Hp1 and Hp2) were designed and the Hp1 was immobilized on the electrode surface, which could form a kissing complex with Hp2 through the apical loop-loop or kissing interaction of the RNA-RNA base sequences. The Hp2 possesses the appended single-stranded tails on each end, which hybridize with the recognition element-conjugated DNA strands to construct a protein responsive switch of Hp2 scaffold...
January 9, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29351348/interactions-of-2-o-methyl-oligoribonucleotides-with-the-rna-models-of-the-30s-subunit-a-site
#9
Maciej Jasiński, Marta Kulik, Monika Wojciechowska, Ryszard Stolarski, Joanna Trylska
Synthetic oligonucleotides targeting functional regions of the prokaryotic rRNA could be promising antimicrobial agents. Indeed, such oligonucleotides were proven to inhibit bacterial growth. 2'-O-methylated (2'-O-Me) oligoribonucleotides with a sequence complementary to the decoding site in 16S rRNA were reported as inhibitors of bacterial translation. However, the binding mode and structures of the formed complexes, as well as the level of selectivity of the oligonucleotides between the prokaryotic and eukaryotic target, were not determined...
2018: PloS One
https://www.readbyqxmd.com/read/29351317/hafts-are-novel-lncrna-transcripts-from-aflatoxin-exposure
#10
B Alex Merrick, Justin S Chang, Dhiral P Phadke, Meredith A Bostrom, Ruchir R Shah, Xinguo Wang, Oksana Gordon, Garron M Wright
The transcriptome can reveal insights into precancer biology. We recently conducted RNA-Seq analysis on liver RNA from male rats exposed to the carcinogen, aflatoxin B1 (AFB1), for 90 days prior to liver tumor onset. Among >1,000 differentially expressed transcripts, several novel, unannotated Cufflinks-assembled transcripts, or HAfTs (Hepatic Aflatoxin Transcripts) were found. We hypothesized PCR-cloning and RACE (rapid amplification of cDNA ends) could further HAfT identification. Sanger data was obtained for 6 transcripts by PCR and 16 transcripts by 5'- and 3'-RACE...
2018: PloS One
https://www.readbyqxmd.com/read/29348408/nipbl-haploinsufficiency-reveals-a-constellation-of-transcriptome-disruptions-in-the-pluripotent-and-cardiac-states
#11
Jason A Mills, Pamela S Herrera, Maninder Kaur, Lanfranco Leo, Deborah McEldrew, Jesus A Tintos-Hernandez, Ramakrishnan Rajagopalan, Alyssa Gagne, Zhe Zhang, Xilma R Ortiz-Gonzalez, Ian D Krantz
Cornelia de Lange syndrome (CdLS) is a complex disorder with multiple structural and developmental defects caused by mutations in structural and regulatory proteins involved in the cohesin complex. NIPBL, a cohesin regulatory protein, has been identified as a critical protein responsible for the orchestration of transcriptomic regulatory networks necessary for embryonic development. Mutations in NIPBL are responsible for the majority of cases of CdLS. Through RNA-sequencing of human induced pluripotent stem cells and in vitro-derived cardiomyocytes, we identified hundreds of mRNAs, pseudogenes, and non-coding RNAs with altered expression in NIPBL+/- patient-derived cells...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348366/structures-of-human-prc2-with-its-cofactors-aebp2-and-jarid2
#12
Vignesh Kasinath, Marco Faini, Simon Poepsel, Dvir Reif, Xinyu Ashlee Feng, Goran Stjepanovic, Ruedi Aebersold, Eva Nogales
Transcriptionally repressive histone H3K27 methylation by PRC2 (Polycomb repressive complex 2) is essential for cellular differentiation and development. Here we report cryo-EM structures of human PRC2 in two distinct, active states, while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, while AEBP2 interacts with the RBAP48 subunit mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex...
January 18, 2018: Science
https://www.readbyqxmd.com/read/29348171/a-cationic-c-terminal-patch-and-structural-rearrangements-in-ebola-virus-matrix-vp40-protein-control-its-interactions-with-phosphatidylserine
#13
Kathryn Del Vecchio, Cary T Frick, Jeevan B Gc, Shun-Ichiro Oda, Bernard S Gerstman, Erica Ollmann Saphire, Prem P Chapagain, Robert V Stahelin
Ebola virus (EBOV) is a filamentous lipid-enveloped virus that causes hemorrhagic fever with a high fatality rate. Viral protein 40 (VP40) is the major EBOV matrix protein and regulates viral budding from the plasma membrane. VP40 is a transformer/morpheein that can structurally rearrange its native homodimer into either a hexameric filament that facilitates viral budding or a RNA-binding octameric ring that regulates viral transcription. VP40 associates with plasma-membrane lipids such as phosphatidylserine (PS), and this association is critical to budding from the host cell...
January 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29348170/crispr-rna-and-anti-crispr-protein-binding-to-the-xanthomonas-albilineans-csy1-csy2-heterodimer-in-the-type-i-f-crispr-cas-system
#14
Suji Hong, Donghyun Ka, Seo Jeong Yoon, Nayoung Suh, Migyeong Jeong, Jeong-Yong Suh, Euiyoung Bae
Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins provide microbial adaptive immunity against bacteriophages. In type I-F CRISPR-Cas systems, multiple Cas proteins (Csy1-4) comprise a surveillance complex (Csy complex) with CRISPR RNA (crRNA) for target recognition. Here, we report the biochemical characterization of the Csy1-Csy2 subcomplex from Xanthomonas albilineans, including the analysis of its interaction with crRNA and also AcrF2, an anti-CRISPR (Acr) protein from a phage that infects Pseudomonas aeruginosa The X...
January 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29348140/interactions-localization-and-phosphorylation-of-the-m6a-generating-mettl3-mettl14-wtap-complex
#15
Eva Schöller, Franziska Weichmann, Thomas Treiber, Sam Ringle, Nora Treiber, Andrew Flatley, Regina Feederle, Astrid Bruckmann, Gunter Meister
N6-methyladenine (m6A) is found on many eukaryotic RNAs including mRNAs. M6A modification has been implicated in mRNA stability and turn over, localization or translation efficiency. A heterodimeric enzyme complex composed of METTL3 and METTL14 generates m6A on mRNAs. METTL3/14 is found in the nucleus where it is localized to nuclear speckles and the splicing regulator WTAP is required for this distinct nuclear localization pattern. Although recent crystal structures revealed how the catalytic MT-A70 domains of METTL3 and METTL14 interact with each other, a more global architecture including WTAP and RNA interactions has not been reported so far...
January 18, 2018: RNA
https://www.readbyqxmd.com/read/29348055/high-resolution-structures-of-mitochondrial-ribosomes-and-their-functional-implications
#16
REVIEW
Philipp Bieri, Basil J Greber, Nenad Ban
Mitochondrial ribosomes (mitoribosomes) almost exclusively synthesize essential components of the oxidative phosphorylation machinery. Dysfunction of mitochondrial protein biosynthesis leads to human diseases and plays an important role in the altered metabolism of cancer cells. Recent developments in cryo-electron microscopy enabled the structural characterization of complete yeast and mammalian mitoribosomes at near-atomic resolution. Despite originating from ancestral bacterial ribosomes, mitoribosomes have diverged in their composition and architecture...
January 15, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29347817/biochemical-basis-of-apobec3-deoxycytidine-deaminase-activity-on-diverse-dna-substrates
#17
Madison B Adolph, Robin P Love, Linda Chelico
The Apolipoprotein B mRNA editing complex (APOBEC) family of enzymes are single-stranded polynucleotide cytidine deaminases. These enzymes catalyze the deamination of cytidine in RNA or single-stranded DNA, which forms uracil. From this eleven member enzyme family in humans, the deamination of single-stranded DNA by the seven APOBEC3 family members are considered here. The APOBEC3 family has many roles such as, restricting endogenous and exogenous retrovirus replication and retrotransposon insertion events and reducing DNA-induced inflammation...
January 18, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29346760/single-cell-transcriptional-profiling-reveals-cellular-diversity-and-intercommunication-in-the-mouse-heart
#18
Daniel A Skelly, Galen T Squiers, Micheal A McLellan, Mohan T Bolisetty, Paul Robson, Nadia A Rosenthal, Alexander R Pinto
Characterization of the cardiac cellulome, the network of cells that form the heart, is essential for understanding cardiac development and normal organ function and for formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our understanding of cardiac cellular composition and highlighted important functional roles for non-myocyte cell types. In this study, we characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing (scRNA-seq)...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346615/the-rna-splicing-endonuclease-from-the-euryarchaeaon-methanopyrus-kandleri-is-a-heterotetramer-with-constrained-substrate-specificity
#19
Ayano Kaneta, Kosuke Fujishima, Wataru Morikazu, Hiroyuki Hori, Akira Hirata
Four different types (α4, α'2, (αβ)2 and ε2) of RNA-splicing endonucleases (EndAs) for RNA processing are known to exist in the Archaea. Only the (αβ)2 and ε2 types can cleave non-canonical introns in precursor (pre)-tRNA. Both enzyme types possess an insert associated with a specific loop, allowing broad substrate specificity in the catalytic α units. Here, the hyperthermophilic euryarchaeon Methanopyrus kandleri (MKA) was predicted to harbor an (αβ)2-type EndA lacking the specific loop. To characterize MKA EndA enzymatic activity, we constructed a fusion protein derived from MKA α and β subunits (fMKA EndA)...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29346407/relaxin-reverses-inflammatory-and-immune-signals-in-aged-hearts
#20
Brian Martin, Beth Ann Gabris-Weber, Rajiv Reddy, Guillermo Romero, Ansuman Chattopadhyay, Guy Salama
BACKGROUND: 'Healthy' aging drives structural and functional changes in the heart including maladaptive electrical remodeling, fibrosis and inflammation, which lower the threshold for cardiovascular diseases such as heart failure (HF) and atrial fibrillation (AF). Despite mixed results in recent clinical trials, Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post-treatment, in patients with acute decompensated HF. Relaxin's short life-span (hours) but long-lasting protective actions led us to test the hypothesis that relaxin acts at a genomic level to reverse maladaptive remodeling in aging and HF...
2018: PloS One
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