CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets

Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.     

Nano-to-micro scale dynamics of P-selectin detachment from leukocyte interfaces. III. Numerical simulation of tethering under flow

Transient capture of cells or model microspheres from flow over substrates sparsely coated with adhesive ligands has provided significant insight into the unbinding kinetics of leukocyte:endothelium adhesion complexes under external force. Whenever a cell is stopped by a point attachment, the full hydrodynamic load is applied to the adhesion site within an exceptionally short time-less than the reciprocal of the hydrodynamic shear rate (e.g., typically <0.01 s). The decay in numbers of cells or beads that remain attached to a surface has been used as a measure of the kinetics of molecular bond dissociation under constant force, revealing a modest increase in detachment rate at growing applied shear stresses. On the other hand, when detached under steady ramps of force with mechanical probes (e.g., the atomic force microscope and biomembrane force probe), P-selectin:PSGL-1 adhesion bonds break at rates that increase enormously under rising force, yielding 100-fold faster off rates at force levels comparable to high shear. The comparatively weak effect of force on tether survival in flow chamber experiments could be explained by a possible partition of the load amongst several bonds. However, a comprehensive understanding of the difference in kinetic behavior requires us to also inspect other factors affecting the dynamics of attachment-force buildup, such as the interfacial compliance of all linkages supporting the adhesion complex. Here, combining the mechanical properties of the leukocyte interface measured in probe tests with single-bond kinetics and the kinetics of cytoskeletal dissociation, we show that for the leukocyte adhesion complex P-selectin:PSGL-1, a detailed adhesive dynamics simulation accurately reproduces the tethering behavior of cells observed in flow chambers. Surprisingly, a mixture of 10% single bonds and 90% dimeric bonds is sufficient to fully match the data of the P-selectin:PSGL-1 experiments, with the calculated decay in fraction of attached cells still appearing exponential.     

C-banding pattern and polymorphism of Aegilops caudata and chromosomal constitutions of the amphiploid T. aestivum — Ae. caudata and six derived chromosome addition lines

Summary C-banding patterns were analysed in 19 different accessions of Aegilops caudata (= Ae. markgrafii, = Triticum dichasians) (2n = 14, genomically CC) from Turkey, Greece and the USSR, and a generalized C-banded karyotype was established. Chromosome specific C-bands are present in all C-genome chromosomes, allowing the identification of each of the seven chromosome pairs. While only minor variations in the C-banding pattern was observed within the accessions, a large amount of polymorphic variation was found between different accessions. C-banding analysis was carried out to identify Ae. caudata chromosomes in the amphiploid Triticum aestivum cv Alcedo — Ae. caudata and in six derived chromosome addition lines. The results show that the amphiploid carries the complete Ae. Caudate chromosome complement and that the addition lines I, II, III, IV, V and VIII carry the Ae. caudata chromosome pairs B, C, D, F, E and G, respectively. One of the two SAT chromosome pairs (A) is missing from the set. C-banding patterns of the added Ae. caudata chromosomes are identical to those present in the ancestor species, indicating that these chromosomes are not structurally rearranged. The results are discussed with respect to the homoeologous relationships of the Ae. caudata chromosomes.     

Aminopyrazine CB1 receptor inverse agonists

A series of 5,6-diaryl-2-amino-pyrazines were prepared and found to have antagonist-like properties at the CB1 receptor. Subsequent SAR studies optimized both receptor potency and drug-like properties including solubility and Cytochrome-P450 inhibition potential. Optimized compounds were demonstrated to be inverse agonists and compared in vivo with rimonabant for their ability to inhibit food intake, to occupy central CB1 receptors and to influence hormonal markers associated with obesity.     

Experimental and modelling studies of drought‐adaptive root architectural traits in wheat (Triticum aestivum L.)

Abstract

This paper presents an interdisciplinary approach to crop improvement that links physiology with plant breeding and simulation modelling to enhance the selection of high‐yielding, drought‐tolerant varieties. In a series of field experiments in Queensland, Australia, we found that the yield of CIMMYT wheat line SeriM82 ranged from 6% to 28% greater than the current cultivar Hartog. Physiological studies on the adaptive traits revealed that SeriM82 had a narrower root architecture and extracted more soil moisture, particularly deep in the profile. Results of a simulation analysis of these adaptive root traits with the cropping system model APSIM for a range of rain‐fed environments in southern Queensland indicated a mean relative yield benefit of 14.5% in water‐deficit seasons. Furthermore, each additional millimetre of water extracted during grain filling generated an extra 55 kg ha^?1 of grain yield. Further root studies of a large number of wheat genotypes revealed that wheat root architecture is closely linked to the angle of seminal roots at the seedling stage – a trait which is suitable for large‐scale and cost‐effective screening programmes. Overall, our results suggest that an interdisciplinary approach to crop improvement is likely to enhance the rate of yield improvement in rain‐fed crops.     

Catchment-Scale Conservation Units Identified for the Threatened Yarra Pygmy Perch (Nannoperca obscura) in Highly Modified River Systems

Habitat fragmentation caused by human activities alters metapopulation dynamics and decreases biological connectivity through reduced migration and gene flow, leading to lowered levels of population genetic diversity and to local extinctions. The threatened Yarra pygmy perch, Nannoperca obscura, is a poor disperser found in small, isolated populations in wetlands and streams of southeastern Australia. Modifications to natural flow regimes in anthropogenically-impacted river systems have recently reduced the amount of habitat for this species and likely further limited its opportunity to disperse. We employed highly resolving microsatellite DNA markers to assess genetic variation, population structure and the spatial scale that dispersal takes place across the distribution of this freshwater fish and used this information to identify conservation units for management. The levels of genetic variation found for N. obscura are amongst the lowest reported for a fish species (mean heterozygosity of 0.318 and mean allelic richness of 1.92). We identified very strong population genetic structure, nil to little evidence of recent migration among demes and a minimum of 11 units for conservation management, hierarchically nested within four major genetic lineages. A combination of spatial analytical methods revealed hierarchical genetic structure corresponding with catchment boundaries and also demonstrated significant isolation by riverine distance. Our findings have implications for the national recovery plan of this species by demonstrating that N. obscura populations should be managed at a catchment level and highlighting the need to restore habitat and avoid further alteration of the natural hydrology.     

A review of projection radiography of plasma and biological objects in X-Pinch radiation

A review of studies on the X-pinch as a radiation source for X-ray projection shadow radiography (XPSR) and X-ray absorption spectroscopy (XAS) is presented. The ultimate capabilities of the techniques and ways of their achievement are considered. XPSR has been successfully used to study high-energy-density plasma objects, in particular, exploding wires and wire arrays. Using XPSR, the internal structure and dynamics of a wire explosion and wire array implosion have been investigated for the first time, which has made it possible to develop an adequate consistent theory of the processes occurring in the wire loads of generators with currents from several units of kiloamperes to a few tens of megamperes. The use of XAS for diagnostics of wire loads has allowed one for the first time to measure the parameters of matter in the wire core and plasma corona of the load. X-ray images of various biological objects have obtained, including those with the use of the phase contrast method. This review is a logical continuation of the review “Х-Pinch” [Plasma Phys. Rep. 41, 319, 493 (2015)], in which the Х-pinch as a physical object was considered.     

Fluorescence-based analysis of the intracytoplasmic membranes of type I methanotrophs

Most methanotrophic bacteria maintain intracytoplasmic membranes which house the methane-oxidizing enzyme, particulate methane monooxygenase. Previous studies have primarily used transmission electron microscopy or cryo-electron microscopy to look at the structure of these membranes or lipid extraction methods to determine the per cent of cell dry weight composed of lipids. We show an alternative approach using lipophilic membrane probes and other fluorescent dyes to assess the extent of intracytoplasmic membrane formation in living cells. This fluorescence method is sensitive enough to show not only the characteristic shift in intracytoplasmic membrane formation that is present when methanotrophs are grown with or without copper, but also differences in intracytoplasmic membrane levels at intermediate copper concentrations. This technique can also be employed to monitor dynamic intracytoplasmic membrane changes in the same cell in real time under changing growth conditions. We anticipate that this approach will be of use to researchers wishing to visualize intracytoplasmic membranes who may not have access to electron microscopes. It will also have the capability to relate membrane changes in individual living cells to other measurements by fluorescence labelling or other single-cell analysis methods.     

The role of the Y chromosome in human evolutionary studies

Analyses of molecular genetic data have added a new dimension to human evolutionary research. Pioneering studies of variation in human populations were based on analyses of blood groups¹ and electromorphs,² both of which represent qualitative multistate phenotypes. With the development of recombinant DNA methods in the 1970s and 1980s, the focus shifted from gene products to a new and plentiful source of human variability, restriction fragment length polymorphisms (RFLPs).^3,4 Finally, the addition of DNA sequencining survey data to the rapidly growing RFLP data base made it feasible for the first time to determine the exact number of nucleotide substitutions between different alleles, as well as to construct gene trees and reconstruct the phylogenetic history of populations.^5–7     

A Comparative Study of Primary Production and Related Factors in Four Saline Lakes in Victoria,Australia

The purpose of the study was to compare the primary plankton productivities of lakes of different salinities and to determine the causative factors involved in their production rates. Four lakes (specific conductivity —mS cm⁻¹ at 18°C) were initially chosen: Coragulac (9), Red Rock (25), Corangamite (38), Pink (250). Sampling and production measurements were made every two to three weeks. Three lakes were dominated by specific phytoplankton blooms: Red Rock (Anabaena spiroides), Corangamite (Nodularia spumigena). Pink (Dunaliella salina). Coragulac Lake had more diverse populations. Red Rock Tarn had some of the highest production values ever recorded. Extremely high soluble phosphate and inorganic carbon concentrations were the most important causative factors. Pink Lake had very low production rates. High salinity and low nutrient concentrations were limiting factors. The other lakes were intermediate in production and nutrient levels. Zooplankton populations were also determined.