A5069552100- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Pain Mechanisms and Treatments
- Advanced biosensing and bioanalysis techniques
- Cancer-related molecular mechanisms research
- Neuropeptides and Animal Physiology
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Ion channel regulation and function
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Bacterial Genetics and Biotechnology
- COVID-19 epidemiological studies
- Evolution and Genetic Dynamics
- Viral Infectious Diseases and Gene Expression in Insects
- SARS-CoV-2 and COVID-19 Research
- MicroRNA in disease regulation
- Vaccine Coverage and Hesitancy
- Virology and Viral Diseases
- CRISPR and Genetic Engineering
National Institutes of Health
2014-2025
National Center for Biotechnology Information
2014-2024
United States National Library of Medicine
2024
University of North Carolina at Chapel Hill
2006-2015
University of Toronto
2015
McGill University Health Centre
2015
McGill University
2015
Center for Drug Evaluation and Research
2013
United States Food and Drug Administration
2013
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2010
Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened sensitivity. We identified three genetic variants (haplotypes) gene encoding catecholamine- O -methyltransferase (COMT) we designated as low (LPS), average (APS) and high (HPS). show these haplotypes encompass 96% population, five combinations strongly associated ( P =0.0004) with variation in to experimental pain. The presence...
All archaeal and many bacterial genomes contain Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR) variable arrays of the CRISPR-associated (cas) genes that have been previously implicated in a novel form DNA repair on basis comparative analysis their protein product sequences. However, proximity CRISPR cas strongly suggests they related functions which is hard to reconcile with hypothesis.The sequences numerous gene products were classified into approximately 25 distinct...
Catechol- O -methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common haplotypes the human COMT gene, divergent in two synonymous one nonsynonymous position, code for differences enzymatic activity are associated with sensitivity. Haplotypes changes exhibited largest difference activity, due to reduced amount translated protein. The major varied respect messenger RNA local stem-loop structures, such that most stable structure was...
Small, hydrophobic proteins whose synthesis is repressed by small RNAs (sRNAs), denoted type I toxin–antitoxin modules, were first discovered on plasmids where they regulate plasmid stability, but subsequently found a few bacterial chromosomes. We used exhaustive PSI-BLAST and TBLASTN searches across 774 genomes to identify homologs of known toxins. These substantially expanded the collection predicted toxins, revealed homology Ldr Fst suggested that loci are not spread horizontal gene...
In enteric bacteria, the transcription factor σ E maintains membrane homeostasis by inducing synthesis of proteins involved in repair and two small regulatory RNAs (sRNAs) that down-regulate abundant porins. Here, we describe discovery a third -dependent sRNA, MicL (mRNA-interfering complementary RNA regulator Lpp), transcribed from promoter located within coding sequence cutC gene. is synthesized as 308-nucleotide (nt) primary transcript processed to an 80-nt form. Both forms possess...
The parameters of the spontaneous deleterious mutation process remain poorly known, despite their importance. Here, we report results a accumulation experiment performed on panmictic populations Drosophila melanogaster without any genetic manipulations. Two experimental were kept for 30 generations under relaxed natural selection. Each generation, 100 pairs formed randomly, and every fecund pair contributed son daughter to next generation. Comparison with two controls, one cryopreserved...
Single-stranded mRNA molecules form secondary structures through complementary self-interactions. Several hypotheses have been proposed on the relationship between nucleotide sequence, encoded amino acid sequence and structure. We performed first transcriptome-wide in silico analysis of human mouse foldings found a pronounced periodic pattern involvement show that this is created by structure genetic code, dinucleotide relative abundances are important for maintenance Although synonymous...
The mammalian cytoskeletal proteins β- and γ-actin are highly homologous, but only β-actin is amino-terminally arginylated in vivo, which regulates its function. We examined the metabolic fate of exogenously expressed nonarginylated actin isoforms. Arginylated γ-actin, unlike β-, was unstable selectively ubiquitinated degraded vivo. This instability regulated by differences nucleotide coding sequence between two isoforms, conferred different translation rates. translated more slowly than...
Abstract Adrenergic receptor β 2 (ADRB2) is a primary target for epinephrine. It plays critical role in mediating physiological and psychological responses to environmental stressors. Thus, functional genetic variants of ADRB2 will be associated with complex array phenotypes. These should also interact factors such as physical or emotional stress produce phenotype vulnerable pathological states. In this study, we determined whether common contribute the development chronic pain condition...
The μ-opioid receptor (OPRM1) is the principal target for both endogenous and exogenous opioid analgesics. There are substantial individual differences in human responses to painful stimuli opiate drugs that attributed genetic variations OPRM1. In searching new functional variants, we employed comparative genome analysis obtained evidence existence of an expanded OPRM1 gene locus with promoters, alternative exons regulatory elements. Examination polymorphisms within identified strong...
Small interfering RNAs (siRNAs) have become an important tool in cell and molecular biology. Reliable design of siRNA molecules is essential for the needs large functional genomics projects.To improve efficient molecules, we performed a comparative, thermodynamic correlation analysis on heterogeneous set 653 siRNAs collected from literature. We used this training to select features optimize computational models. identified 18 parameters that correlate significantly with silencing efficiency....
Current literature describes several methods for the design of efficient siRNAs with 19 perfectly matched base pairs and 2 nt overhangs. Using four independent databases totaling 3336 experimentally verified siRNAs, we compared how well these predict siRNA cleavage efficiency. According to receiver operating characteristics (ROC) correlation analyses, best programs were BioPredsi, ThermoComposition DSIR. We also studied individual parameters that significantly consistently correlated...
The 1,021,348 base pair genome sequence of the Acanthamoeba polyphaga moumouvirus, a new member Mimiviridae family infecting polyphaga, is reported. moumouvirus represents third lineage beside mimivirus and megavirus. Thereby, it recently proposed Megavirales order. This giant virus was isolated from cooling tower water in southeastern France but most closely related to Megavirus chiliensis, which ocean off coast Chile. predicted encode 930 proteins, 879 have detectable homologs. Among these...
Specific structures in mRNA modulate translation rate and thus can affect protein folding. Using the from two eukaryotes three prokaryotes, we explore connections between compactness, inferred solvent accessibility, structure, folding energy (ΔG). In both prokaryotes eukaryotes, ΔG value of most stable 30 nucleotide segment (ΔGmin) strongly, positively correlates with accessibility. Thus, mRNAs containing exceptionally secondary structure elements typically encode compact proteins. The...
Burkholderia mallei (Bm), the causative agent of predominately equine disease glanders, is a genetically uniform species that very closely related to much more diverse pseudomallei (Bp), an opportunistic human pathogen and primary cause melioidosis. To gain insight into relative lack genetic diversity within Bm, we performed whole-genome comparative analysis seven Bm strains contrasted these with eight Bp strains. The core genome (shared by all strains) smaller in size than Bp, but inverse...
Mammalian genomes contain numerous genes for long noncoding RNAs (lncRNAs). The functions of the lncRNAs remain largely unknown but their evolution appears to be constrained by purifying selection, albeit relatively weakly. To gain insights into mode and functional range lncRNA, they can compared with much better characterized protein-coding genes. evolutionary rate shows a universal negative correlation expression: highly expressed are on average more conserved during than lower expression...
The genome sequence of the Mamavirus, a new Acanthamoeba polyphaga mimivirus strain, is reported. With 1,191,693 nt in length and 1,023 predicted protein-coding genes, Mamavirus has largest among known viruses. genomes previously described Mimivirus are highly similar both genes intergenic regions. However, contains an extra 5′-terminal segment that encompasses primarily disrupted duplicates present elsewhere genome. also several unique including small regulatory polyA polymerase subunit...