Chemically Related 4,5-Linked Aminoglycoside Antibiotics Drive Subunit Rotation in Opposite Directions

Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin-paromomycin, ribostamycin and neamine-each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6\u27-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6\u27-substituent and the drug\u27s net positive charge. By solving the crystal structure of the paromomycin-ribosome complex, we observe specific contacts between the apical tip of H69 and the 6\u27-hydroxyl on paromomycin from within the drug\u27s canonical h44-binding site. These results indicate that aminoglycoside actions must be framed in the context of bridge B2 and their regulation of subunit rotation

A revised scheme for the reactivity of iron (oxyhydr)oxide minerals towards dissolved sulfide

The reaction between dissolved sulfide and synthetic iron (oxyhydr)oxide minerals was studied in artificial seawater and 0.1 M NaCl at pH 7.5 and 25°C. Electron transfer between surface-complexed sulfide and solid phase Fe(III) results in the oxidation of dissolved sulfide to elemental sulfur, and the subsequent dissolution of the surface-reduced Fe. Sulfide oxidation and Fe(II) dissolution kinetics were evaluated for freshly precipitated hydrous ferric oxide (HFO), lepidocrocite, goethite, magnetite, hematite, and Al-substituted lepidocrocite. Reaction kinetics were expressed in terms of an empirical rate equation of the form: R-i = k(i)(H2S)(t=0)(0.5)A where Ri is the rate of Fe(II) dissolution (RFe) or the rate of sulfide oxidation (RS), ki is the appropriate rate constant (kFe or kS), (H2S)t=0 is the initial dissolved sulfide concentration, and A is the initial mineral surface area. The rate constants derived from the above equation suggest that the reactivity of Fe (oxyhydr)oxide minerals varies over two orders of magnitude, with increasing reactivity in the order, goethite < hematite < magnetite << lepidocrocite ≈ HFO. Competitive adsorption of major seawater solutes has little effect on reaction kinetics for the most reactive minerals, but results in rates which are reduced by 65-80% for goethite, magnetite, and hematite. This decrease in reaction rates likely arises from the blocking of surface sites for sulfide complexation by the adsorption of seawater solutes during the later, slower stages of adsorption (possibly attributable to diffusion into micropores or aggregates). The derivation of half lives for the sulfide-promoted reductive dissolution of Fe (oxyhydr)oxides in seawater, suggests that mineral reactivity can broadly be considered in terms of two mineral groups. Minerals with a lower degree of crystal order (hydrous ferric oxides and lepidocrocite) are reactive on a time-scale of minutes to hours. The more ordered minerals (goethite, magnetite, and hematite) are reactive on a time-scale of tens of days. Substitution of impurities within the mineral structure (as is likely in nature) has an effect on mineral reactivity. However, these effects are unlikely to have a significant impact on the relative reactivities of the two mineral groups

An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response.

The Retinoid-related orphan receptor beta (RORβ) gene encodes a developmental transcription factor and has 2 predominant isoforms created through alternative first exon usage; one specific to the retina and another present more broadly in the central nervous system, particularly regions involved in sensory processing. RORβ belongs to the nuclear receptor family and plays important roles in cell fate specification in the retina and cortical layer formation. In mice, loss of RORβ causes disorganized retina layers, postnatal degeneration, and production of immature cone photoreceptors. Hyperflexion or high-stepping of rear limbs caused by reduced presynaptic inhibition by Rorb-expressing inhibitory interneurons of the spinal cord is evident in RORβ-deficient mice. RORβ variants in patients are associated with susceptibility to various neurodevelopmental conditions, primarily generalized epilepsies, but including intellectual disability, bipolar, and autism spectrum disorders. The mechanisms by which RORβ variants confer susceptibility to these neurodevelopmental disorders are unknown but may involve aberrant neural circuit formation and hyperexcitability during development. Here we report an allelic series in 5 strains of spontaneous Rorb mutant mice with a high-stepping gait phenotype. We show retinal abnormalities in a subset of these mutants and demonstrate significant differences in various behavioral phenotypes related to cognition. Gene expression analyses in all 5 mutants reveal a shared over-representation of the unfolded protein response and pathways related to endoplasmic reticulum stress, suggesting a possible mechanism of susceptibility relevant to patients

Something in the atmosphere? Michael Chekhov, Deirdre Hurst Du Prey, and a web of practices between acting and dance

This article contextualises principles of Chekhov’s technique within convergent developments in dance by bringing into focus the interesting web of connections between Chekhov’s female colleagues — specifically his associate Deirdre Hurst Du Prey — and key pioneers in the field of dance and dance-mime, including Mary Wigman, Isadora Duncan, Martha Graham and Margaret Barr. Their cross-connections broaden our view on the canon of embodied theatre practice, and also open up reflection on how overlaps between acting- and dance principles may be useful for contemporary embodied theatre practice and its efforts to work across these currently (in the Western conservatoire context) quite segregated disciplines

Working With the Tangible: Radiation, A Twenty-First Century Interpretation

The intangible means of expression was a topic of investigation across various disciplines when Michael Chekhov was developing his pedagogic practice. In the world of science, Harold Saxton Burr and Albert Szent-Gyorgi, were examining the body as a conductor of energy. Their research was relevant to Chekhov's approach regarding how the actor communicates with internal and external stimulus. This article begins with an analysis of Chekhov's theories on Radiation, it moves on to offer insights into science and energy work with reference to cell Biologist James Oschman and his concept of ‘the living matrix’ and Mae Wan Ho's critique of quantum cohesion. Examples of praxis demonstrate that contemporary science and body work can provide a greater understanding of how Radiation and the organisation of energy can enhance performance

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Methanethiol-dependent dimethylsulfide production in soil environments

Dimethylsulfide (DMS) is an environmentally important trace gas with roles in sulfur cycling, signalling to higher organisms and in atmospheric chemistry. DMS is believed to be predominantly produced in marine environments via microbial degradation of the osmolyte dimethylsulfoniopropionate (DMSP). However, significant amounts of DMS are also generated from terrestrial environments, for example, peat bogs can emit ~6 μmol DMS m−2 per day, likely via the methylation of methanethiol (MeSH). A methyltransferase enzyme termed ‘MddA’, which catalyses the methylation of MeSH, generating DMS, in a wide range of bacteria and some cyanobacteria, may mediate this process, as the mddA gene is abundant in terrestrial metagenomes. This is the first study investigating the functionality of MeSH-dependent DMS production (Mdd) in a wide range of aerobic environments. All soils and marine sediment samples tested produced DMS when incubated with MeSH. Cultivation-dependent and cultivation-independent methods were used to assess microbial community changes in response to MeSH addition in a grassland soil where 35.9% of the bacteria were predicted to contain mddA. Bacteria of the genus Methylotenera were enriched in the presence of MeSH. Furthermore, many novel Mdd+ bacterial strains were isolated. Despite the abundance of mddA in the grassland soil, the Mdd pathway may not be a significant source of DMS in this environment as MeSH addition was required to detect DMS at only very low conversion rates