scholarly journals Human Brain Shows Recurrent Non-Canonical MicroRNA Editing Events Enriched for Seed Sequence with Possible Functional Consequence

2020 ◽  
Vol 6 (2) ◽  
pp. 21
Author(s):  
Deepanjan Paul ◽  
Asgar Hussain Ansari ◽  
Megha Lal ◽  
Arijit Mukhopadhyay
Keyword(s):  
Human Brain ◽  
Small Rna Sequencing ◽  
Sequence Motifs ◽  
Seed Sequence ◽  
Contributing Factors ◽  
Editing Event ◽  
Specific Sequence ◽  
Functional Consequence ◽  
Three Samples ◽  
Normal Individuals

RNA editing is a post-transcriptional modification, which can provide tissue-specific functions not encoded in DNA. Adenosine-to-inosine is the predominant editing event and, along with cytosine-to-uracil changes, constitutes canonical editing. The rest is non-canonical editing. In this study, we have analysed non-canonical editing of microRNAs in the human brain. We have performed massively parallel small RNA sequencing of frontal cortex (FC) and corpus callosum (CC) pairs from nine normal individuals (post-mortem). We found 113 and 90 unique non-canonical editing events in FC and CC samples, respectively. More than 70% of events were in the miRNA seed sequence—implicating an altered set of target mRNAs and possibly resulting in a functional consequence. Up to 15% of these events were recurring and found in at least three samples, also supporting the biological relevance of such variations. Two specific sequence variations, C-to-A and G-to-U, accounted for over 80% of non-canonical miRNA editing events—and revealed preferred sequence motifs. Our study is one of the first reporting non-canonical editing in miRNAs in the human brain. Our results implicate miRNA non-canonical editing as one of the contributing factors towards transcriptomic diversity in the human brain.

scholarly journals Analysis of the Genetic Variability of Virulence-Related Loci in Epidemic Clones of Methicillin-Resistant Staphylococcus aureus

2005 ◽  
Vol 49 (1) ◽  
pp. 366-379 ◽  
Author(s):  
A. R. Gomes ◽  
S. Vinga ◽  
M. Zavolan ◽  
H. de Lencastre
Keyword(s):  
Staphylococcus Aureus ◽  
Genetic Variability ◽  
Amino Acid Level ◽  
Point Of View ◽  
Sequence Motifs ◽  
Related Factors ◽  
Specific Sequence ◽  
Methicillin Resistant ◽  
Sequence Types ◽  
R Domain

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) isolates have previously been classified into major epidemic clonal types by pulsed-field gel electrophoresis in combination with multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec typing. We aimed to investigate whether genetic variability in potentially polymorphic domains of virulence-related factors could provide another level of differentiation in a diverse collection of epidemic MRSA clones. The target regions of strains representative of epidemic clones and genetically related methicillin-susceptible S. aureus isolates from the 1960s that were sequenced included the R domains of clfA and clfB; the D, W, and M regions of fnbA and fnbB; and three regions in the agr operon. Sequence variation ranged from very conserved regions, such as those for RNAIII and the agr interpromoter region, to the highly polymorphic R regions of the clf genes. The sequences of the clf R domains could be grouped into six major sequence types on the basis of the sequences in their 3′ regions. Six sequence types were also observed for the fnb sequences at the amino acid level. From an evolutionary point of view, it was interesting that a small DNA stretch at the 3′ clf R-domain sequence and the fnb sequences agreed with the results of MLST for this set of strains. In particular, clfB R-domain sequences, which had a high discriminatory capacity and with which the types distinguished were congruent with those obtained by other molecular typing methods, have potential for use for the typing of S. aureus. Clone- and strain-specific sequence motifs in the clf and fnb genes may represent useful additions to a typing methodology with a DNA array.

scholarly journals Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bertrand Beckert ◽  
Elodie C. Leroy ◽  
Shanmugapriya Sothiselvam ◽  
Lars V. Bock ◽  
Maxim S. Svetlov ◽  
...  
Keyword(s):  
Antibiotic Resistance Genes ◽  
Structural Basis ◽  
Sequence Motifs ◽  
Specific Sequence ◽  
Bacterial Ribosome ◽  
Translational Arrest ◽  
Exit Tunnel ◽  
Mechanistic Basis ◽  
Dynamics Simulations ◽  
Context Specific

AbstractMacrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these antibiotics are known to interrupt translation at specific sequence motifs, with ketolides predominantly stalling at Arg/Lys-X-Arg/Lys motifs and macrolides displaying a broader specificity, a structural basis for their context-specific action has been lacking. Here, we present structures of ribosomes arrested during the synthesis of an Arg-Leu-Arg sequence by the macrolide erythromycin (ERY) and the ketolide telithromycin (TEL). Together with deep mutagenesis and molecular dynamics simulations, the structures reveal how ERY and TEL interplay with the Arg-Leu-Arg motif to induce translational arrest and illuminate the basis for the less stringent sequence-specific action of ERY over TEL. Because programmed stalling at the Arg/Lys-X-Arg/Lys motifs is used to activate expression of antibiotic resistance genes, our study also provides important insights for future development of improved macrolide antibiotics.

scholarly journals Age-dependent formation of TMEM106B amyloid filaments in human brain

2021 ◽  
Author(s):  
Manuel Schweighauser ◽  
Diana Arseni ◽  
Melissa Huang ◽  
Sofia Lövestam ◽  
Yang Shi ◽  
...  
Keyword(s):  
Human Brain ◽  
Transmembrane Protein ◽  
Amyloid Β ◽  
Dependent Manner ◽  
Type Ii ◽  
Western Blots ◽  
Normal Individuals ◽  
Age Dependent ◽  
Neurologically Normal ◽  
Filamentous Inclusions

Many age-dependent neurodegenerative diseases, like Alzheimer's and Parkinson's, are characterised by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-β (Aβ), α-synuclein and TDP-43 are the most common. Here, we used electron cryo-microscopy (cryo-EM) structure determination to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in the human brain. We solved cryo-EM structures of TMEM106B filaments from the brains of 22 individuals with neurodegenerative conditions, including sporadic and inherited tauopathies, Aβ-amyloidoses, synucleinopathies and TDP-43opathies, as well as from the brains of two neurologically normal individuals. We observed three different TMEM106B folds, with no clear relationship between folds and diseases. The presence of TMEM106B filaments correlated with that of a 29 kDa sarkosyl-insoluble fragment of the protein on Western blots. The presence of TMEM106B filaments in the brains of older, but not younger, neurologically normal individuals indicates that they form in an age-dependent manner.

scholarly journals Discovery of an ancient MHC category with both class I and class II features

2021 ◽  
Vol 118 (51) ◽  
pp. e2108104118
Author(s):  
Kazuhiko Okamura ◽  
Johannes M. Dijkstra ◽  
Kentaro Tsukamoto ◽  
Unni Grimholt ◽  
Geert F. Wiegertjes ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Class Ii ◽  
Class I ◽  
Sequence Motifs ◽  
Critical Question ◽  
Specific Sequence ◽  
Mhc Molecules ◽  
Mhc Class I Molecule ◽  
Chain Organization ◽  
Lymphocyte Populations

Two classes of major histocompatibility complex (MHC) molecules, MHC class I and class II, play important roles in our immune system, presenting antigens to functionally distinct T lymphocyte populations. However, the origin of this essential MHC class divergence is poorly understood. Here, we discovered a category of MHC molecules (W-category) in the most primitive jawed vertebrates, cartilaginous fish, and also in bony fish and tetrapods. W-category, surprisingly, possesses class II–type α- and β-chain organization together with class I–specific sequence motifs for interdomain binding, and the W-category α2 domain shows unprecedented, phylogenetic similarity with β2-microglobulin of class I. Based on the results, we propose a model in which the ancestral MHC class I molecule evolved from class II–type W-category. The discovery of the ancient MHC group, W-category, sheds a light on the long-standing critical question of the MHC class divergence and suggests that class II type came first.

Two-dimensional gel electrophoresis of human brain proteins. I. Technique and nomenclature of proteins.

1982 ◽  
Vol 28 (4) ◽  
pp. 782-789 ◽  
Author(s):  
D E Comings
Keyword(s):  
Human Brain ◽  
Gel Electrophoresis ◽  
Urea Solution ◽  
Two Dimensional ◽  
Two Dimensional Gel Electrophoresis ◽  
Polypeptide Patterns ◽  
Normal Individuals ◽  
Molecular Masses ◽  
Group B ◽  
The Individual

Abstract To understand at a molecular level the basis of the normal and pathological genetic differences between individuals it is necessary to begin a detailed two-dimensional gel electrophoretic mapping of the proteins of the human brain in normal individuals and those with various genetic neurological disorders. The present study is an examination of the polypeptide patterns of extracts of the human brain made with 9 mol/L urea solution. Details of the technique and the nomenclature of the patterns obtained are presented. the gels are separated into 20 sub-sections, based on standards with known molecular masses and isoelectric points. Groups of polypeptides within these sub-sections are identified by a number and a letter; the individual proteins are identified by a number. Thus, protein 1 in subsection 8, group b, would be designated 8b: 1. Subsequent papers in this series identify many of these proteins; show which proteins belong to the cytosol, synaptosome, myelin, and other brain fractions; show how these patterns vary between normal individuals and those with different neurological and psychiatric conditions; examine the effect of severe gliosis; and present the results of non-equilibrium gel electrophoresis for the more basic proteins.

Application of chemometric analysis for identifying pollution sources: a case study on the River Adyar, India

2009 ◽  
Vol 60 (12) ◽  
pp. 1254 ◽  
Author(s):  
T. Venugopal ◽  
L. Giridharan ◽  
M. Jayaprakash
Keyword(s):  
Factor Analysis ◽  
River Water ◽  
Saline Water ◽  
Anthropogenic Activities ◽  
Pollution Level ◽  
Seasonal Effect ◽  
Contributing Factors ◽  
Sources Of Pollution ◽  
Three Samples ◽  
River Adyar

The various factors responsible for the chemical budget and pollution of river water have been evaluated and characterised using various statistical tools. The potential sources of pollution that alter the chemical composition of River Adyar water have been identified and quantified. Thirty-three samples were collected from the River Adyar and basic chemical parameters and heavy metals were interpreted by the systematic application of statistical techniques. The relationships among the various ions were examined and the sources of origin were evaluated using correlation studies. An R-mode factor analysis revealed that the chemistry of the river water largely depends on anthropogenic activities, rock–water interaction and saline water intrusion. A cluster analysis was applied and the major and minor clusters for pre-monsoon and post-monsoon seasons were classified. This classification was found to be in line with the results of the R-mode factor analysis. Seasonal variation in the chemistry and pollution level of the river water was clearly indicated by both cluster and factor analyses. Factor scores, which give vital information on the variation of the factors by station, were successfully applied. The contributing factors and any seasonal effect on the stations were evaluated and interpreted.

scholarly journals Using a Simple Cellular Assay to Map NES Motifs in Cancer-Related Proteins, Gain Insight into CRM1-Mediated NES Export, and Search for NES-Harboring Micropeptides

2020 ◽  
Vol 21 (17) ◽  
pp. 6341
Author(s):  
Maria Sendino ◽  
Miren Josu Omaetxebarria ◽  
Gorka Prieto ◽  
Jose Antonio Rodriguez
Keyword(s):  
Nuclear Export ◽  
Relevant Information ◽  
Sequence Motifs ◽  
Specific Sequence ◽  
Cellular Assay ◽  
Small Proteins ◽  
Binding Groove ◽  
Related Proteins ◽  
Insight Into

The nuclear export receptor CRM1 (XPO1) recognizes and binds specific sequence motifs termed nuclear export signals (NESs) in cargo proteins. About 200 NES motifs have been identified, but over a thousand human proteins are potential CRM1 cargos, and most of their NESs remain to be identified. On the other hand, the interaction of NES peptides with the “NES-binding groove” of CRM1 was studied in detail using structural and biochemical analyses, but a better understanding of CRM1 function requires further investigation of how the results from these in vitro studies translate into actual NES export in a cellular context. Here we show that a simple cellular assay, based on a recently described reporter (SRVB/A), can be applied to identify novel potential NESs motifs, and to obtain relevant information on different aspects of CRM1-mediated NES export. Using cellular assays, we first map 19 new sequence motifs with nuclear export activity in 14 cancer-related proteins that are potential CRM1 cargos. Next, we investigate the effect of mutations in individual NES-binding groove residues, providing further insight into CRM1-mediated NES export. Finally, we extend the search for CRM1-dependent NESs to a recently uncovered, but potentially vast, set of small proteins called micropeptides. By doing so, we report the first NES-harboring human micropeptides.

Identification of specific sequence motifs in the upstream region of 242 human miRNA genes

2007 ◽  
Vol 31 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Atsushi Inouchi ◽  
Shuichi Shinohara ◽  
Hiroshi Inoue ◽  
Kenji Kita ◽  
Mitsuo Itakura
Keyword(s):  
Upstream Region ◽  
Sequence Motifs ◽  
Specific Sequence ◽  
Mirna Genes

scholarly journals Flow Cytometry-Assisted Cloning of Specific Sequence Motifs from Complex 16S rRNA Gene Libraries

2004 ◽  
Vol 70 (12) ◽  
pp. 7550-7554 ◽  
Author(s):  
Jeppe L. Nielsen ◽  
Andreas Schramm ◽  
Anne E. Bernhard ◽  
Gerrit J. van den Engh ◽  
David A. Stahl
Keyword(s):  
Flow Cytometry ◽  
16S Rrna ◽  
Cell Sorting ◽  
16S Rrna Genes ◽  
Rapid Screening ◽  
Rrna Genes ◽  
Rrna Gene ◽  
Sequence Motifs ◽  
Specific Sequence ◽  
Gene Libraries

ABSTRACT A flow cytometry method was developed for rapid screening and recovery of cloned DNA containing common sequence motifs. This approach, termed fluorescence-activated cell sorting-assisted cloning, was used to recover sequences affiliated with a unique lineage within the Bacteroidetes not abundant in a clone library of environmental 16S rRNA genes.

scholarly journals Correlation between mazEF Toxin-Antitoxin System Expression and Methicillin Susceptibility in Staphylococcus aureus and Its Relation to Biofilm-Formation

2021 ◽  
Vol 9 (11) ◽  
pp. 2274
Author(s):  
Aya Abd El rahman ◽  
Yasmine El kholy ◽  
Rania Y. Shash
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Methicillin Resistance ◽  
Diffusion Method ◽  
P Value ◽  
Sequence Motifs ◽  
University Hospitals ◽  
Specific Sequence ◽  
Disk Diffusion Method ◽  
Cellular Mrnas

Methicillin resistance in Staphylococcus aureus has become prevalent globally. Moreover, biofilm-formation makes it more difficult to eradicate bacteria by antibiotics. The mazEF toxin-antitoxin system encodes for mazF, which acts as an endoribonuclease that cleaves cellular mRNAs at specific sequence motifs (ACA), and mazE, which opposes the mazF action. Our goal was to detect mazEF expression in methicillin-resistant S. aureus (MRSA) isolates compared with methicillin-sensitive S. aureus (MSSA) isolates and determine its relation to methicillin susceptibility as well as biofilm-formation. According to their susceptibility to cefoxitin disks, 100 S. aureus isolates obtained from patients admitted to Cairo University Hospitals were categorized into 50 MSSA and 50 MRSA according to their susceptibility to cefoxitin disks (30 µg). Antimicrobial susceptibility and biofilm-formation were investigated using the disk diffusion method and tissue culture plate method, respectively. Finally, using real-time PCR, mazEF expression was estimated and correlated to methicillin susceptibility and biofilm formation. Both MRSA and MSSA isolates showed the best sensitivity results with linezolid and gentamicin, where about 88% of MRSA isolates and 96% of MSSA isolates were sensitive to linezolid while 76% of MRSA isolates and 84% of MSSA isolates were sensitive to gentamicin. MRSA isolates were significantly more able to form biofilm than MSSA isolates (p-value = 0.037). The mazEF expression was significantly correlated to methicillin resistance in S. aureus (p-value < 0.001), but not to biofilm-formation.

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