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https://www.readbyqxmd.com/read/27926995/frozen-but-no-accident-why-the-20-standard-amino-acids-were-selected
#1
REVIEW
Andrew J Doig
The 20 standard amino acids encoded by the Genetic Code were adopted during the RNA World, around 4 billion years ago. This amino acid set could be regarded as a frozen accident, implying that other possible structures could equally well have been chosen to use in proteins. Amino acids were not primarily selected for their ability to support catalysis, since the RNA World already had highly effective cofactors to perform reactions, such as oxidation, reduction and transfer of small molecules. Rather, they were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926523/long-non-coding-rna-neat1-overexpression-is-associated-with-poor-prognosis-in-cancer-patients-a-systematic-review-and-meta-analysis
#2
Chao Yang, Zhuo Li, Yajun Li, Rui Xu, Yongfeng Wang, Yu Tian, Wei Chen
OBJECTIVES: Long non-coding RNAs (lncRNAs) are playing important roles in cancer progression and metastasis. Recent studies have demonstrated that the lncRNA, nuclear paraspeckle assembly transcript 1 (NEAT1), was aberrantly up-regulated in various types of cancers and was reported to be associated with unfavorable prognosis in cancer patients. This study examined the relationship between NEAT1 and relevant clinical outcomes. RESULTS: A total of 1354 patients from 11 eligible studies were included in the meta-analysis...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27924986/a-nasba-on-microgel-tethered-molecular-beacon-microarray-for-real-time-microbial-molecular-diagnostics
#3
Y Ma, X Dai, T Hong, G B Munk, M Libera
Despite their many advantages and successes, molecular beacon (MB) hybridization probes have not been extensively used in microarray formats because of the complicating probe-substrate interactions that increase the background intensity. We have previously shown that tethering to surface-patterned microgels is an effective means for localizing MB probes to specific surface locations in a microarray format while simultaneously maintaining them in as water-like an environment as possible and minimizing probe-surface interactions...
December 7, 2016: Analyst
https://www.readbyqxmd.com/read/27924642/development-of-an-rt-qpcr-assay-for-the-specific-detection-of-a-distinct-genetic-lineage-of-the-infectious-bursal-disease-virus
#4
Gonzalo Tomás, Martín Hernández, Ana Marandino, Claudia Techera, Sofia Grecco, Diego Hernández, Alejandro Banda, Yanina Panzera, Ruben Pérez
The infectious bursal disease virus (IBDV) is a major health threat to the world's poultry industry despite intensive controls including proper biosafety practices and vaccination. IBDV (Avibirnavirus, Birnaviridae) is a non-enveloped virus with a bisegmented double-stranded RNA genome. The virus is traditionally classified into classic, variant and very virulent strains, each with different epidemiological relevance and clinical implications. Recently, a novel worldwide spread genetic lineage was described and denoted as distinct (d) IBDV...
December 7, 2016: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/27924586/rna-sequencing-analysis-of-salivary-extracellular-rna
#5
Blanca Majem, Feng Li, Jie Sun, David T W Wong
Salivary biomarkers for disease detection, diagnostic and prognostic assessments have become increasingly well established in recent years. In this chapter we explain the current leading technology that has been used to characterize salivary non-coding RNAs (ncRNAs) from the extracellular RNA (exRNA) fraction: HiSeq from Illumina® platform for RNA sequencing. Therefore, the chapter is divided into two main sections regarding the type of the library constructed (small and long ncRNA libraries), from saliva collection, RNA extraction and quantification to cDNA library generation and corresponding QCs...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924491/single-molecule-fluorescence-energy-transfer-assays-for-the-characterization-of-reaction-pathways-of-mirna-argonaute-complex
#6
Myung Hyun Jo, Sungchul Hohng
Argonaute proteins are key components of the microRNA-induced silencing complexes (miRISCs) that mediate the posttranscriptional gene silencing of microRNAs and small interfering RNA (siRNAs). The complex reaction mechanism of miRISC is expected to be characterized by tracing the reaction pathways of miRISC at the single-molecule level in real time. In this chapter, we describe single-molecule fluorescence resonance energy transfer (FRET) assays to observe the target binding and reaction pathways of miRISC composed of a recombinant Argonaute and a small RNA...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924489/kinetic-analysis-of-target-rna-binding-and-slicing-by-human-argonaute-2-protein
#7
Sarah Willkomm, Tobias Restle
Analyzing the mechanisms of Argonaute-mediated gene silencing is essential to the understanding of RNA interference (RNAi). RNAi is a process to regulate gene expression on a posttranscriptional level. Directed by single-stranded small RNA guides, Argonaute 2 binds complementary target RNAs, and if the guide displays full complementarity to the targeted sequence, Argonaute 2 slices the bound target RNA. This on the one hand is an important mechanism to regulate gene expression in the cell and on the other hand represents a powerful tool to interfere with harmful gene expression levels...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924485/small-molecules-targeting-the-mirna-binding-domain-of-argonaute-2-from-computer-aided-molecular-design-to-rna-immunoprecipitation
#8
Teresa Bellissimo, Silvia Masciarelli, Elena Poser, Ilaria Genovese, Alberto Del Rio, Gianni Colotti, Francesco Fazi
The development of small-molecule-based target therapy design for human disease and cancer is object of growing attention. Recently, specific microRNA (miRNA) mimicking compounds able to bind the miRNA-binding domain of Argonaute 2 protein (AGO2) to inhibit miRNA loading and its functional activity were described. Computer-aided molecular design techniques and RNA immunoprecipitation represent suitable approaches to identify and experimentally determine if a compound is able to impair the loading of miRNAs on AGO2 protein...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924483/rapid-generation-of-mirna-inhibitor-leads-by-bioinformatics-and-efficient-high-throughput-screening-methods
#9
Christopher L Haga, Sai Pradeep Velagapudi, Jessica L Childs-Disney, Jacqueline Strivelli, Matthew D Disney, Donald G Phinney
The discovery of microRNAs (miRNAs) has opened an entire new avenue for drug development. These short (15-22 nucleotides) noncoding RNAs, which function in RNA silencing and posttranscriptional regulation of gene expression, have been shown to critically affect numerous pathways in both development and disease progression. Current miRNA drug development focuses on either reintroducing the miRNA into cells through the use of a miRNA mimic or inhibiting its function via use of a synthetic antagomir. Although these methods have shown some success as therapeutics, they face challenges particularly with regard to cellular uptake and for use as systemic reagents...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924481/machine-learning-approaches-toward-building-predictive-models-for-small-molecule-modulators-of-mirna-and-its-utility-in-virtual-screening-of-molecular-databases
#10
Vinita Periwal, Vinod Scaria
The ubiquitous role of microRNAs (miRNAs) in a number of pathological processes has suggested that they could act as potential drug targets. RNA-binding small molecules offer an attractive means for modulating miRNA function. The availability of bioassay data sets for a variety of biological assays and molecules in public domain provides a new opportunity toward utilizing them to create models and further utilize them for in silico virtual screening approaches to prioritize or assign potential functions for small molecules...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924480/design-of-multimodal-small-molecules-targeting-mirnas-biogenesis-synthesis-and-in-vitro-evaluation
#11
Duc D Vo, Maria Duca
microRNAs (miRNAs) are emerging as novel biological targets for medicinal chemists to develop chemical tools for intracellular regulation. In this context, the discovery of small-molecule drugs targeting specific miRNAs and modulating their production or function represents a very promising approach that could be further developed for targeted therapy in miRNA-related pathologies. Here, we describe the design of multimodal small molecules as RNA ligands targeting DICER-mediated miRNA maturation. The synthesis and the biochemical evaluation as ligands of stem-loop-structured precursor microRNAs (pre-miRNAs) are reported...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924471/mirna-targeting-drugs-the-next-blockbusters
#12
Marco F Schmidt
Only 20 years after the discovery of small non-coding, single-stranded ribonucleic acids, so-called microRNAs (miRNAs), as post-transcriptional gene regulators, the first miRNA-targeting drug Miravirsen for the treatment of hepatitis C has been successfully tested in clinical Phase II trials. Addressing miRNAs as drug targets may enable the cure, or at least the treatment of diseases, which presently seems impossible. However, due to miRNAs' chemical structure, generation of potential drug molecules with necessary pharmacokinetic properties is still challenging and requires a re-thinking of the drug discovery process...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924063/%C3%AE-np63%C3%AE-and-micrornas-leveraging-the-epithelial-mesenchymal-transition
#13
REVIEW
Andrew J Stacy, Michael P Craig, Suraj Sakaram, Madhavi Kadakia
The epithelial-mesenchymal transition (EMT) is a cellular reprogramming mechanism that is an underlying cause of cancer metastasis. Recent investigations have uncovered an intricate network of regulation involving the TGFβ, Wnt, and Notch signaling pathways and small regulatory RNA species called microRNAs (miRNAs). The activity of a transcription factor vital to the maintenance of epithelial stemness, ΔNp63α, has been shown to modulate the activity of these EMT pathways to either repress or promote EMT...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27924026/tetools-facilitates-big-data-expression-analysis-of-transposable-elements-and-reveals-an-antagonism-between-their-activity-and-that-of-pirna-genes
#14
Emmanuelle Lerat, Marie Fablet, Laurent Modolo, Hélène Lopez-Maestre, Cristina Vieira
Over recent decades, substantial efforts have been made to understand the interactions between host genomes and transposable elements (TEs). The impact of TEs on the regulation of host genes is well known, with TEs acting as platforms of regulatory sequences. Nevertheless, due to their repetitive nature it is considerably hard to integrate TE analysis into genome-wide studies. Here, we developed a specific tool for the analysis of TE expression: TEtools This tool takes into account the TE sequence diversity of the genome, it can be applied to unannotated or unassembled genomes and is freely available under the GPL3 (https://github...
October 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923992/sinorhizobium-meliloti-ybey-is-an-endoribonuclease-with-unprecedented-catalytic-features-acting-as-silencing-enzyme-in-riboregulation
#15
Margarida Saramago, Alexandra Peregrina, Marta Robledo, Rute G Matos, Rolf Hilker, Javier Serrania, Anke Becker, Cecilia M Arraiano, José I Jiménez-Zurdo
Structural and biochemical features suggest that the almost ubiquitous bacterial YbeY protein may serve catalytic and/or Hfq-like protective functions central to small RNA (sRNA)-mediated regulation and RNA metabolism. We have biochemically and genetically characterized the YbeY ortholog of the legume symbiont Sinorhizobium meliloti (SmYbeY). Co-immunoprecipitation (CoIP) with a FLAG-tagged SmYbeY yielded a poor enrichment in RNA species, compared to Hfq CoIP-RNA uncovered previously by a similar experimental setup...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923747/ibulocydine-sensitizes-human-hepatocellular-carcinoma-cells-to-trail-induced-apoptosis-via-calpain-mediated-bax-cleavage
#16
Seok Soon Park, Eunjin Jwa, Seol Hwa Shin, Eun Jin Ju, Intae Park, Jhang Ho Pak, Jung Jin Hwang, Dong-Hyung Cho, B Moon Kim, Sung-Bae Kim, Jung Shin Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi
Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells without affecting the majority of normal human cells. However, hepatocellular carcinoma (HCC) cells often display resistance to TRAIL-induced apoptosis. Ibulocydine (IB) is an isobutyrate ester pro-drug of a novel synthetic Cdk inhibitor that targets Cdk7 and Cdk9. In this study, we show that treatment with subtoxic doses of IB in combination with TRAIL displays potent cytotoxicity in TRAIL-resistant human HCC cells...
December 3, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27923655/development-of-a-novel-catalytic-amyloid-displaying-a-metal-dependent-atpase-like-activity
#17
Octavio Monasterio, Esteban Nova, Rodrigo Diaz-Espinoza
Amyloids are protein aggregates of highly regular structure that are involved in diverse pathologies such as Alzheimer's and Parkinson's disease. Recent evidence has shown that under certain conditions, small peptides can self-assemble into amyloids that exhibit catalytic reactivity towards certain compounds. Here we report a novel peptide with a sequence derived from the active site of RNA polymerase that displays hydrolytic activity towards ATP. The catalytic reaction proceeds in the presence of the divalent metal manganese and the products are ADP and AMP...
December 3, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27923454/micrornas-in-the-thyroid
#18
REVIEW
Myriem Boufraqech, Joanna Klubo-Gwiezdzinska, Electron Kebebew
MicroRNAs (miRNAs) are small non-coding RNA comprising approximately 19-25 nucleotides. miRNAs can act as tumour suppressors or oncogenes, and aberrant expression of miRNAs has been reported in several human cancers and has been associated with cancer initiation and progression. Recent evidence suggests that miRNAs play a major role in thyroid carcinogenesis. In this review, we summarize the role of miRNAs in thyroid cancer and describe the oncogenic or tumour suppressor function of miRNAs as well as their clinical utility as prognostic or diagnostic markers in thyroid cancer...
October 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/27923064/sparse-regression-based-structure-learning-of-stochastic-reaction-networks-from-single-cell-snapshot-time-series
#19
Anna Klimovskaia, Stefan Ganscha, Manfred Claassen
Stochastic chemical reaction networks constitute a model class to quantitatively describe dynamics and cell-to-cell variability in biological systems. The topology of these networks typically is only partially characterized due to experimental limitations. Current approaches for refining network topology are based on the explicit enumeration of alternative topologies and are therefore restricted to small problem instances with almost complete knowledge. We propose the reactionet lasso, a computational procedure that derives a stepwise sparse regression approach on the basis of the Chemical Master Equation, enabling large-scale structure learning for reaction networks by implicitly accounting for billions of topology variants...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27922681/cxcr4-promotes-cisplatin-resistance-of-non-small-cell-lung-cancer-in-a-cyp1b1-dependent-manner
#20
Songping Xie, Zhenbo Tu, Jie Xiong, Ganjun Kang, Lina Zhao, Weidong Hu, Haiyan Tan, Kingsley Miyanda Tembo, Qianshan Ding, Xinzhou Deng, Jie Huang, Qiuping Zhang
Chemoresistance is the main cause of treatment failure and high mortality in advanced lung cancer. Cisplatin, an important chemotherapeutic agent for lung cancer, has been observed to show enormously reduced chemotherapeutic efficacy owing to the development of chemoresistance. CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in non-small cell lung cancer (NSCLC) tissues and participates in cancer progression by regulating cell growth, apoptosis or invasion. In this study, we therefore investigated whether CXCR4 plays a role in the cisplatin associated resistance in NSCLC...
December 2, 2016: Oncology Reports
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