Defining Immune Engagement Thresholds for In Vivo Control of Virus-Driven Lymphoproliferation

Persistent infections are subject to constant surveillance by CD8⁺ cytotoxic T cells (CTL). Their control should therefore depend on MHC class I-restricted epitope presentation. Many epitopes are described for γ-herpesviruses and form a basis for prospective immunotherapies and vaccines. However the quantitative requirements of in vivo immune control for epitope presentation and recognition remain poorly defined. We used Murid Herpesvirus-4 (MuHV-4) to determine for a latently expressed viral epitope how MHC class-I binding and CTL functional avidity impact on host colonization. Tracking MuHV-4 recombinants that differed only in epitope presentation, we found little latitude for sub-optimal MHC class I binding before immune control failed. By contrast, control remained effective across a wide range of T cell functional avidities. Thus, we could define critical engagement thresholds for the in vivo immune control of virus-driven B cell proliferation.     

Species’ traits influence ground beetle responses to farm and landscape level agricultural intensification in Europe

Agricultural intensification may result in important shifts in insect community composition and function, but this remains poorly explored. Studying how groups of species with shared traits respond to local and landscape scale land-use management can reveal mechanisms behind such observed impacts. We tested if ground beetles (Coleoptera: Carabidae) divided into trait groups based on body sizes, wing morphologies and dietary preferences respond differently to farming practise (organic and conventional), farming intensity (measured as yield) and landscape complexity (measured as the proportion of arable land within a 1,000 m radius) across Europe. We used data from 143 farms in five regions in northern and central Europe. Organic farms did not differ in abundance or richness of any trait group compared to conventional farms. As farm scale intensity (yield) increased, overall abundance of beetles decreased, but abundances of small and medium sized beetles, as well as that of wingless beetles, were unaffected. Overall species richness was not affected by yield, whereas consideration of traits revealed that phytophagous and omnivorous beetles were less species rich on farms with high yields. Increasing the proportion of arable land in the landscape increased overall beetle abundance. This was driven by an increase in omnivorous beetles. The total species richness was not affected by an increase in the proportion arable land, although the richness of wingless beetles was found to increase. Potential effects on ecosystem functioning need to be taken into account when designing schemes to maintain agricultural biodiversity, because species with different ecological traits respond differently to local management and landscape changes.     

A Comparison of Social Bee–Plant Networks between Two Urban Areas

In the last decade, several studies demonstrated the effectiveness of ecological network analysis to a better understanding of the structure bee–plant interaction networks; however, such approaches involving urban areas are still scarce. Here, we analyzed two assemblages of corbiculate bees (Apoidea, Apidae) in two geographically distinct urban areas in Brazil. In both study areas, apid bees visiting flowers were captured with an insect net. Surveys were performed biweekly and alternately in each area, over a 1-year period. Both urban areas were very similar for most indices. The two social bee–plant networks were significantly nested, a pattern usually described for bee–plant networks and somehow expected in our study, considering the recognized behavior of social apid bees in exploring a wide range of plant species. The modularity measures were low and very similar for the networks of both urban areas, a finding that could be due at least in part to the low phylogenetic distance between corbiculate bees and the broad dietary habits of the social apid bees. Network-level indices showed that both bee assemblages had a relatively low niche overlap, indicating that the set of social apid species studied exploited differently the arrays of plants available. Species level index (resource range) showed that in both urban areas, Trigona spinipes (Fabr.) and Apis mellifera L. showed the higher number of interactions, a result that demonstrates the importance of these species in social bee–plant interaction networks in urban areas. Similarly to other ecosystems, these two apid species behaved as super-generalists in the two urban areas surveyed herein.     

DNA binding ligands with excellent antibiotic potency against drug-resistant gram-positive bacteria

An efficient synthesis of DNA binding molecules consisting of four heterocyclic carboxamide units and various substituents at both termini is described. The minor-groove binding ligands showed excellent activity against a broad range of Gram-positive bacteria; no cross-resistance to known antibacterial drugs was observed.     

Dental caries in a Portuguese identified skeletal sample from the late 19th and early 20th centuries

Dental caries was investigated in 600 adult dentitions belonging to the identified osteological collections of the Museum of Anthropology, University of Coimbra, Portugal (late 19th/early 20th centuries). The main advantage of this sample compared to an archaeological source is the presence of known demographic parameters such as age, sex, and occupation. The aim of this study is to investigate the issues involved in comparing caries data derived from archaeological death assemblages with statistics compiled from clinical studies of the living. When only the upper dentition was considered, higher rates were observed in females than in males. No differences were found between sexes for lower teeth. In both sexes, both the percentage of carious teeth and the severity of lesions were found to increase with age, demonstrating that caries activity continued throughout life. The slight decrease observed for the age group 70–79 years is probably due to the increased antemortem tooth loss in the elderly. Caries was most common at contact areas (32.9%) and rarest at smooth crown surfaces (6.5%). Root surface caries was graphed in relation to the exposure of roots, and it was confirmed that the degree of root exposure was not strongly related to the frequency of carious lesions on the exposed root surface, although both increased with age. Molars were attacked more frequently by caries as a whole than premolars, canines or incisors. The results are similar to studies of recent living populations with a limited access to professional dental care. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

Land use history and site location are more important for grassland species richness than local soil properties

Lately there has been a shift in Sweden from grazing species‐rich semi‐natural grasslands towards grazing ex‐arable fields in the modern agricultural landscape. Grazing ex‐arable fields contain a fraction of the plant species richness confined to semi‐natural grasslands. Still, they have been suggested as potential target sites for re‐creation of semi‐natural grasslands. We asked to what extent does fine‐scale variation in soil conditions, management history and site location effect local plant diversity in grazed ex‐arable fields. We examined local soil conditions such as texture, pH, organic carbon, nitrogen (N) and extractable phosphate (P) and effects on plant richness in ten pairs of grazed ex‐fields and neighbouring semi‐natural grasslands in different rural landscapes. Each grassland pair where in the same paddock. A multivariate test showed that site location and land use history explained more of differences in species richness than local soil property variables. Plant species richness was positively associated to grazed ex‐fields with low pH, low N and P levels. Sites with high plant richness in semi‐natural grasslands also had more species in the adjacent grazed ex‐fields, compared to sites neighbouring less species‐rich semi‐natural grasslands. Although both soil properties and species richness were different in grazed ex‐fields compared to semi‐natural grassland, the site location within a landscape, and vicinity to species‐rich grasslands, can override effects of soil properties. In conclusion, if properly located, ex‐arable fields may be an important habitat to maintain plant diversity at larger spatio‐temporal scales and should considered as potential sites for grassland restoration.     

Combined chelation of bi-functional bis-hydroxypiridinone and mono-hydroxypiridinone: Synthesis, solution and in vivo evaluation

3-Hydroxy-4-pyridinones (3,4-HP) are well known iron-chelators with applications in medicinal chemistry, mainly associated with their high affinity towards trivalent hard metal ions (e.g. M³⁺, M = Fe, Al, Ga) and use as decorporating agents in situations of metal accumulation. The polydenticity and the extra-functionality of 3,4-HP derivatives have been explored, aimed at improving the chelating efficacy and the selectivity of the interaction with specific biological receptors. However, the ideal conjugation of both features in one molecular unity usually leads to high molecular weight compounds which can have crossing-membrane limitations.Herein, a different approach is used combining a arylpiperazine-containing bis-hydroxypyridone (H₂L¹) with a biomimetic mono-hydroxypyridinone, ornithine-derivative (HL²), to assess the potential coadjuvating effect that could result from the administration of both compounds for the decorporation of hard metal ions. This work reports the results of solution and in vivo studies on their chelating efficacy either as a simple binary or a ternary system (H₂L¹:HL²:M³⁺), using potentiometric and spectrophotometric methods. The solution complexation studies with Fe(III) indicate that the solubility of the complexes is considerably increased in the ternary system, an important feature for the metal complex excretion, upon the metal sequestration. The results of the in vivo studies with ⁶⁷Ga-injected mice show differences on the biodistribution profiles of the radiotracer, upon the administration of each chelating agent, that are mainly ascribed to the differences of their extra-functional groups and lipo/hydrophilic character. However, administration of both chelating agents leads to a more steady metal mobilization, which may be attributed to an improved access to different cellular compartments.     

The HSP90 binding mode of a radicicol-like E-oxime determined by docking,binding free energy estimations,and NMR N chemical shifts

We determine the binding mode of a macrocyclic radicicol-like oxime to yeast HSP90 by combining computer simulations and experimental measurements. We sample the macrocyclic scaffold of the unbound ligand by parallel tempering simulations and dock the most populated conformations to yeast HSP90. Docking poses are then evaluated by the use of binding free energy estimations with the linear interaction energy method. Comparison of QM/MM-calculated NMR chemical shifts with experimental shift data for a selective subset of backbone ¹⁵N provides an additional evaluation criteria. As a final test we check the binding modes against available structure–activity-relationships. We find that the most likely binding mode of the oxime to yeast HSP90 is very similar to the known structure of the radicicol–HSP90 complex.