Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: an analysis of x-ray crystal structures

The potential of RNA molecules to be used as therapeutic targets by small inhibitors is now well established. In this fascinating wide-open field, aminoglycoside antibiotics constitute the most studied family of RNA binding drugs. Within the last three years, several x-ray crystal structures were solved for aminoglycosides complexed to one of their main natural targets in the bacterial cell, the decoding aminoacyl-tRNA site (A site). Other crystallographic structures have revealed the binding modes of aminoglycosides to the three existing types of resistance-associated enzymes. The present review summarizes the various aspects of the molecular recognition of aminoglycosides by these natural RNA or protein receptors. The analysis and the comparisons of the detailed interactions offer insights that are helpful in designing new generations of antibiotics.     

Alien futures: What is on the horizon for biological invasions?

Aim

To collect and identify the issues that may affect the future global and local management of biological invasions in the next 20–50 years and provide guidance for the prioritization of actions and policies responding to the management challenges of the future.

Location

Global

Methods

We used an open online survey to poll specialists and stakeholders from around the world as to their opinion on the three most important future issues both globally and at their respective local working level.

Results

The 240 respondents identified 629 global issues that we categorized into topics. We summarized the highest rated topics into five broad thematic areas: (1) environmental change, particularly climate change, (2) the spread of species through trade, (3) public awareness, (4) the development of new technologies to enhance management and (5) the need to strengthen policies. The respondents also identified 596 issues at their respective local working levels. Management, early detection, prevention and funding‐related issues all ranked higher than at the global level. Our global audience of practitioners, policymakers and researchers also elicited topics not identified in horizon scanning exercises led by scientists including potential human health impacts, the need for better risk assessments and legislation, the role of human migration and water management.

Main conclusions

The topic areas identified in this horizon scan provide guidance where future policy priorities for invasive alien species should be set. First, to reduce the magnitude and speed of environmental change and its impacts on biological invasions; second, to restrict the movement of potentially invasive alien species via trade; third, to raise awareness with the general public and empower them to act; and finally, to invest in innovative technologies that can detect and mitigate adverse impacts of introduced species.

     

Aboveground resilience to species loss but belowground resistance to nitrogen addition in a montane plant community

Aims Decades of empirical work have demonstrated how dominant plant species and nitrogen fertilization can influence the structure and function of plant communities. More recent studies have examined the interplay between these factors, but few such studies use an explicit trait-based framework. In this study, we use an explicit trait-based approach to identify potential mechanisms for community-level responses and to test ecological niche theory.Methods We experimentally manipulated plant communities (control, ?dominant species, ?random biomass) and nitrogen (N) inputs (control, +organic N, +inorganic N) in a fully factorial design. We predicted that traits related to plants' ability to take up different forms of soil N would differ between dominant and subordinate species, resulting in interactive effects of dominant species loss and N fertilization on plant community structure and function. The study took place in a montane meadow in the Rocky Mountains, Colorado, USA.Important findings After four years, the plant community in removal plots converged toward a species composition whose leaf and root functional traits resembled those of the previously removed dominant species. Ecosystem productivity generally increased with N addition: soil carbon efflux was ~50% greater when either form of N was added, while inorganic N addition increased aboveground biomass production by ~60% relative to controls. The increase in production was mediated by increased average height, leaf mass:area ratio and leaf dry matter content in plant communities to which we added inorganic N. Contrary to our predictions, there were no interactive effects of N fertilization and dominant species loss on plant community structure or ecosystem function. The plant community composition in this study exhibited resistance to soil N addition and, given the functional convergence we observed, was resilient to species loss. Together, our results indicate that the ability of species to compensate functionally for species loss confers resilience and maintains diversity in montane meadow communities.     

The cognitive and cultural foundations of moral behavior

Does moral culture contribute to the evolution of cooperation? Here, we examine individuals' and communities' models of what it means to be good and bad and how they correspond to corollary behavior across a variety of socioecological contexts. Our sample includes over 600 people from eight different field sites that include foragers, horticulturalists, herders, and the fully market-reliant. We first examine the universals and particulars of explicit moral models. We then use these moral models to assess their role in the outcome of an economic experiment designed to detect systematic, dishonest rule-breaking favoritism. We show that individuals are slightly more inclined to play by the rules when their moral models include the task-relevant virtues of “honesty” and “dishonesty.” We also find that religious beliefs are better predictors of honest play than these virtues. The predictive power of these values' and beliefs' local prevalence, however, remains inconclusive. In summary, we find that religious beliefs and moral models may help promote honest behavior that may widen the breadth of human cooperation.     

Synchrotron microtomography-based osteohistology of Gansus yumenensis: new data on the evolution of uninterrupted bone deposition in basal birds

Many studies of the limb bones from birds of the major clades reveal a mosaic evolution in morphological characters. From this, we assume that uninterrupted compact bone evolved independently multiple times outside of the crown group. We hypothesise that there are key intraskeletal changes in the osteohistological features, such as the organisation of the vascular network. To test these hypotheses, we analysed and described the osteohistological features of five different midshaft samples of Gansus yumenensis, a non-ornithurine Euornithes from China, based on virtual models obtained from synchrotron microtomography scans, a less invasive method that the traditional physical cross section. We performed quantitative analyses with volume, surface area and estimated ratios. The osteohistological features of Gansus yumenensis were compared with those of stem and crown birds. From our analyses, we discuss the pros/cons of using synchrotron microtomography scans compared to traditional physical cross section. Our analyses demonstrate that Gansus yumenensis is the fourth described extinct Euornithes to exhibit uninterrupted bone deposition in all bone samples, providing further support for multiple origins of this feature outside of the bird crown group. Finally, our osteohistological investigation of Gansus yumenensis provides future study avenues regarding the evolution and development of bone tissue in fossil birds.     

Crystal structure of geneticin bound to a bacterial 16S ribosomal RNA A site oligonucleotide

Aminoglycosides are antibacterial molecules that decrease translation accuracy by binding to the decoding aminoacyl-tRNA site (A site) on 16S ribosomal RNA. We have solved the crystal structure of an RNA fragment containing the A site bound to geneticin at 2.40A resolution. Geneticin, also known as G418, is a gentamicin-related aminoglycoside: it contains three rings that are functionalized by hydroxyl, ammonium and methyl groups. The detailed comparison of the distinctive behaviour of geneticin (binding to pro- and eukaryotic A sites) with the crystallographic, biochemical and microbiological results obtained so far for aminoglycoside-A site complexes offers new insights on the system. The two sugar rings constituting the neamine part common to most of the aminoglycosides bind to the A site, as already observed in the crystal structures solved previously with paromomycin and tobramycin. The essential hydrogen bonds involving ring I (to A1408) and ring II (to the phosphate oxygen atoms of the bulged adenine bases 1492 and 1493 and to G1494) are conserved and additional contacts are observed from ring III (to phosphate oxygen atoms of G1405 and U1406). The present work illustrates a molecular basis of the range in sensitiveness exhibited by geneticin towards common point A site mutations associated to resistance phenotypes. In addition, analysis and comparisons of the structures cast light on the role played by the conserved U1406.U1495 pair in the recognition of the A site by aminoglycosides.