Stochasticity in Protein Levels Drives Colinearity of Gene Order in Metabolic Operons of Escherichia coli

Gene order in some bacterial metabolic operons reflects ordering in the metabolic pathway. That this is true uniquely for operons expressed at low levels highlights the selective importance of fluctuations in protein levels

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Operons

Operons (clusters of co-regulated genes with related functions) are common features of bacterial genomes. More recently, functional gene clustering has been reported in eukaryotes, from yeasts to filamentous fungi, plants, and animals. Gene clusters can consist of paralogous genes that have most likely arisen by gene duplication. However, there are now many examples of eukaryotic gene clusters that contain functionally related but non-homologous genes and that represent functional gene organizations with operon-like features (physical clustering and co-regulation). These include gene clusters for use of different carbon and nitrogen sources in yeasts, for production of antibiotics, toxins, and virulence determinants in filamentous fungi, for production of defense compounds in plants, and for innate and adaptive immunity in animals (the major histocompatibility locus). The aim of this article is to review features of functional gene clusters in prokaryotes and eukaryotes and the significance of clustering for effective function

Diversity of aerobic methanotrophic bacteria in a permafrost active layer soil of the Lena Delta, Siberia

With this study, we present first data on the diversity of aerobic methanotrophic bacteria (MOB) in an Arctic permafrost active layer soil of the Lena Delta, Siberia. Applying denaturing gradient gel electrophoresis and cloning of 16S ribosomal ribonucleic acid (rRNA) and pmoA gene fragments of active layer samples, we found a general restriction of the methanotrophic diversity to sequences closely related to the genera Methylobacter and Methylosarcina, both type I MOB. In contrast, we revealed a distinct species-level diversity. Based on phylogenetic analysis of the 16S rRNA gene, two new clusters of MOB specific for the permafrost active layer soil of this study were found. In total, 8 out of 13 operational taxonomic units detected belong to these clusters. Members of these clusters were closely related to Methylobacter psychrophilus and Methylobacter tundripaludum, both isolated from Arctic environments. A dominance of MOB closely related to M. psychrophilus and M. tundripaludum was confirmed by an additional pmoA gene analysis. We used diversity indices such as the Shannon diversity index or the Chao1 richness estimator in order to compare the MOB community near the surface and near the permafrost table. We determined a similar diversity of the MOB community in both depths and suggest that it is not influenced by the extreme physical and geochemical gradients in the active layer

Microbial communities and processes in Arctic permafrost environments

In polar regions, huge layers of frozen ground, termed permafrost, are formed. Permafrost covers more than 25 % of the land surface and significant parts of the coastal sea shelfs. Its habitats are controlled by extreme climate and terrain conditions. Particularly, the seasonal freezing and thawing in the upper active layer of permafrost leads to distinct gradients in temperature and geochemistry. Microorganisms in permafrost environments have to survive extremely cold temperatures, freeze-thaw cycles, desiccation and starvation under long-lasting background radiation over geological time scales. Although the biology of permafrost microorganisms remains relatively unexplored, recent findings show that microbial communities in this extreme environment are composed by members of all three domains of life (Archaea, Bacteria, Eukarya), with a total biomass comparable to temperate soil ecosystems. This chapter describes the environmental conditions of permafrost and reviews recent studies on microbial processes and diversity in permafrost-affected soils as well as the role and significance of microbial communities with respect to global biogeochemical cycles

Arene-fused 1,2-oxazole N-oxides and derivatives. The impact of the N-O dipole and substitution on their aromatic character and reactivity profile. Can it be a useful structure in synthesis? A theoretical insight

DFT calculations have shown that the N-O dipole of benzene- and naphthalene-fused 1,2-oxazole N-oxides causes a distortion of their σ and π frame, concentrated on the 1,2-oxazole ring, such that it increases its susceptibility to opening. The distortion forces the benzene ring into some diene geometry, thus, reducing π delocalization over the bi- or tricyclic structure and ultimately their aromatic character. C-3 substitution has a marked influence mainly on the naphthalene-fused N-oxides. C-5 and particularly C-6 substitution, as the position of most extended interaction with the N-O dipole through the π ring density, contribute to the distortion of the 1,2-oxazole geometry and thereby to the decrease of aromaticity of the structure. Bond uniformity (IA), average bond order (ABO) and Harmonic Oscillator Model of Aromaticity (HOMA) indices have been recruited to measure aromaticity changes. IA and ABO appear to be more credible to 1,2-benzoxazole N-oxides and 1,2-naphthoxazole N-oxides, respectively, while HOMA has been found equally reliable to both. Hardness and dipole moments follow similar trends. Energies, localization and separation of the four frontiers orbitals, i.e. HO, HO-1, and LU, LU+1, indicate a rather notable aromatic character of the N-oxides. Their reactivity profile, portrayed by descriptors such as Fukui and electro(nucleo)philicity Parr functions, shows good agreement with experimental outcomes towards electrophiles but succumbs to discrepancies towards nucleophiles due to the susceptibility of the hetero-ring to opening. The "push-pull" character of the N-O dipole and more importantly the extent of its double bonding direct site selectivity.Peer reviewe