FARE, a new family of foldback transposons in Arabidopsis

A new family of transposons, FARE, has been identified in Arabidopsis. The structure of these elements is typical of foldback transposons, a distinct subset of mobile DNA elements found in both plants and animals. The ends of FARE elements are long, conserved inverted repeat sequences typically 550 bp in length. These inverted repeats are modular in organization and are predicted to confer extensive secondary structure to the elements. FARE elements are present in high copy number, are heterogeneous in size, and can be divided into two subgroups. FARE1's average 1.1 kb in length and are composed entirely of the long inverted repeats. FARE2's are larger, up to 16.7 kb in length, and contain a large internal region in addition to the inverted repeat ends. The internal region is predicted to encode three proteins, one of which bears homology to a known transposase. FARE1.1 was isolated as an insertion polymorphism between the ecotypes Columbia and Nossen. This, coupled with the presence of 9-bp target-site duplications, strongly suggests that FARE elements have transposed recently. The termini of FARE elements and other foldback transposons are imperfect palindromic sequences, a unique organization that further distinguishes these elements from other mobile DNAs.     

On the origin of the stereoselective affinity of Nutlin-3 geometrical isomers for the MDM2 protein

The stereoselective affinity of small-molecule binding to proteins is typically broadly explained in terms of the thermodynamics of the final bound complex. Using Brownian dynamics simulations, we show that the preferential binding of the MDM2 protein to the geometrical isomers of Nutlin-3, an effective anticancer lead that works by inhibiting the interaction between the proteins p53 and MDM2, can be explained by kinetic arguments related to the formation of the MDM2:Nutlin-3 encounter complex. This is a diffusively bound state that forms prior to the final bound complex. We find that the MDM2 protein stereoselectivity for the Nutlin-3a enantiomer stems largely from the destabilization of the encounter complex of its mirror image enantiomer Nutlin-3b, by the K70 residue that is located away from the binding site. On the other hand, the trans-Nutlin-3a diastereoisomer exhibits a shorter residence time in the vicinity of MDM2 compared with Nutlin-3a due to destabilization of its encounter complex by the collective interaction of pairs of charged residues on either side of the binding site: Glu25 and Lys51 on one side, and Lys94 and Arg97 on the other side. This destabilization is largely due to the electrostatic potential of the trans-Nutlin-3a isomer being largely positive over extended continuous regions around its structure, which are otherwise well-identified into positive and negative regions in the case of the Nutlin-3a isomer. Such rich insight into the binding processes underlying biological selectivity complements the static view derived from the traditional thermodynamic analysis of the final bound complex. This approach, based on an explicit consideration of the dynamics of molecular association, suggests new avenues for kinetics-based anticancer drug development and discovery.     

Synthesis and structural investigations of Ni(II)- and Pd(II)-coordinated α-diimines with chlorinated backbones

Novel square planar Pd(II) α-diimines [PdX₂{ArNC(Cl)}₂], where Ar = C₆H₅, (2,6-Me₂C₆H₃), (2,6-ⁱPr₂C₆H₃) and X = Cl or Br, and the octahedral Ni(II) complex [NiBr₂{(C₆H₅)NC(Cl)}₂(THF)₂] have been prepared and characterised by spectroscopic methods. For two of the Pd(II) complexes and the Ni(II) complex the crystal structures were determined by X-ray crystallography. A further insight into the geometry and electronic structure of [PdBr₂{(2,6-Me₂C₆H₃)NC(Cl)}₂] was gained using density functional theoretical calculations (DFT). This compound resembles structurally and electronically typical olefin polymerisation pre-catalysts supported by α-diimines incorporating methyl- and 1,8-naphtalenyl substituents at the ligand backbone. The chlorine-substituted backbone of the free ligand [2,6-Me₂C₆H₃NC(Cl)]₂ can be employed in further alkylation reactions to generate new multifunctional ligand prototypes with potential uses as ansa-metallocene/diimines building blocks for catalytic applications of heterobimetallic complexes.     

A catchment‐scale perspective of plastic pollution

Plastic pollution is distributed across the globe, but compared with marine environments, there is only rudimentary understanding of the distribution and effects of plastics in other ecosystems. Here, we review the transport and effects of plastics across terrestrial, freshwater and marine environments. We focus on hydrological catchments as well‐defined landscape units that provide an integrating scale at which plastic pollution can be investigated and managed. Diverse processes are responsible for the observed ubiquity of plastic pollution, but sources, fluxes and sinks in river catchments are poorly quantified. Early indications are that rivers are hotspots of plastic pollution, supporting some of the highest recorded concentrations. River systems are also likely pivotal conduits for plastic transport among the terrestrial, floodplain, riparian, benthic and transitional ecosystems with which they connect. Although ecological effects of micro‐ and nanoplastics might arise through a variety of physical and chemical mechanisms, consensus and understanding of their nature, severity and scale are restricted. Furthermore, while individual‐level effects are often graphically represented in public media, knowledge of the extent and severity of the impacts of plastic at population, community and ecosystem levels is limited. Given the potential social, ecological and economic consequences, we call for more comprehensive investigations of plastic pollution in ecosystems to guide effective management action and risk assessment. This is reliant on (a) expanding research to quantify sources, sinks, fluxes and fates of plastics in catchments and transitional waters both independently as a major transport routes to marine ecosystems, (b) improving environmentally relevant dose–response relationships for different organisms and effect pathways, (c) scaling up from studies on individual organisms to populations and ecosystems, where individual effects are shown to cause harm and; (d) improving biomonitoring through developing ecologically relevant metrics based on contemporary plastic research.     

Integration of the genetic and physical maps of the chicken macrochromosomes

A large amount of genetic mapping information has been obtained in the chicken from the East Lansing, Compton and Wageningen reference populations. Physical mapping information has however, been more limited. We have mapped 14 new clones, both genetically and physically, and all 14 have been assigned to macrochromosomes. The orientation of linkage groups E01C01C11W01 (Chr 1), E06C02W02 (Chr 2), E02C03W03 (Chr 3), E05C04W04 (Chr 4), E07E34C05W05 (Chr 5), E11C10W06 (Chr 6), E45C07W07 (Chr 7) and E43C12W11 (Chr 8) has been established. Here we present integrated maps of the eight macrochromosomes and the Z chromosome of the chicken and correlate genetic with physical distances for chromosomes 1-3 and the Z sex chromosome.     

Temperature dependence of electron transfer between bacteriopheophytin and ubiquinone in protonated and deuterated reaction centers of Rhodopseudomonas sphaeroides.

The rate of the electron-transfer reaction between bacteriopheophytin and the first quinone in isolated reaction centers of Rhodopseudomonas sphaeroides has an unusual temperature dependence. The rate increases about threefold with decreasing temperature between 300 and 25 K, and decreases abruptly at temperatures below 25 K. Partial deuteration of the reaction centers alters the temperature dependence of the rate constant. Qualitative features of the temperature dependence can be understood in the context of a theory of nonadiabatic electron transfer (Sarai, 1980. Biochim. Biophys. Acta 589:71-83). We conclude that very low-energy (10-50 cm-1) processes, perhaps skeletal vibrations of the protein, are important to electron transfer. Higher-energy vibrations, possibly involving the pyrrolic N--H bonds of bacteriopheophytin, also are important in this process.     

Modeling of the mechanical function of the human gastroesophageal junction using an anatomically realistic three-dimensional model

The aim of this study was to combine the anatomy and physiology of the human gastroesophageal junction (the junction between the esophagus and the stomach) into a unified computer model. A three-dimensional (3D) computer model of the gastroesophageal junction was created using cross-sectional images from a human cadaver. The governing equations of finite deformation elasticity were incorporated into the 3D model. The model was used to predict the intraluminal pressure values (pressure inside the junction) due to the muscle contraction of the gastroesophageal junction and the effects of the surrounding structures. The intraluminal pressure results obtained from the 3D model were consistent with experimental values available in the literature. The model was also used to examine the independent roles of each muscle layer (circular and longitudinal) of the gastroesophageal junction by contracting them separately. Results showed that the intraluminal pressure values predicted by the model were primarily due to the contraction of the circular muscle layer. If the circular muscle layer was quiescent, the contraction of the longitudinal muscle layer resulted in an expansion of the junction.In conclusion, the model provided reliable predictions of the intraluminal pressure values during the contraction of a normal gastroesophageal junction. The model also provided a framework to examine the role of each muscle layer during the contraction of the gastroesophageal junction.     

Global variation in freshwater physico-chemistry and its influence on chemical toxicity in aquatic wildlife

Chemical pollution is one of the major threats to global freshwater biodiversity and will be exacerbated through changes in temperature and rainfall patterns, acid–base chemistry, and reduced freshwater availability due to climate change. In this review we show how physico-chemical features of natural fresh waters, including pH, temperature, oxygen, carbon dioxide, divalent cations, anions, carbonate alkalinity, salinity and dissolved organic matter, can affect the environmental risk to aquatic wildlife of pollutant chemicals. We evidence how these features of freshwater physico-chemistry directly and/or indirectly affect the solubility, speciation, bioavailability and uptake of chemicals [including via alterations in the trans-epithelial electric potential (TEP) across the gills or skin] as well as the internal physiology/biochemistry of the organisms, and hence ultimately toxicity. We also show how toxicity can vary with species and ontogeny. We use a new database of global freshwater chemistry (GLORICH) to demonstrate the huge variability (often >1000-fold) for these physico-chemical variables in natural fresh waters, and hence their importance to ecotoxicology. We emphasise that a better understanding of chemical toxicity and more accurate environmental risk assessment requires greater consideration of the natural water physico-chemistry in which the organisms we seek to protect live.