Phenotypic and genotypic analysis of benzimidazole resistance in reciprocal genetic crosses of Haemonchus contortus

Haemonchus contortus is arguably one of the most economically important and ubiquitous parasites of livestock globally and commonly involved in cases of anthelmintic resistance. Here, we performed reciprocal genetic crosses using susceptible (MHco3(ISE)) and multiple anthelmintic resistant (MHco18(UGA2004)) H. contortus isolates. Resultant admixed populations were designated MHco3/18 or MHco18/3, where the lead isolate reflects the origin of the females. Three independent filial generations were generated for each cross, which were subjected to bioassays, molecular approaches and population genetic analyses to investigate the phenotypic and genotypic inheritance of benzimidazole (BZ) resistance at each stage. A panel of microsatellite markers confirmed the success of the genetic cross as markers from both parents were seen in the F(1) crosses. Egg hatch tests revealed a stark difference between the two F(1) crosses with ED(50) estimates for MHco18/3 being 9 times greater than those for MHco3/18. Resistance factors based on ED(50) estimates ranged from 6 to 57 fold in the filial progeny compared to MHco3(ISE) parents. Molecular analysis of the F167Y and F200Y SNP markers associated with BZ resistance were analysed by pyrosequencing and MiSeq deep amplicon sequencing, which showed that MHco3/18.F(1) and MHco18/3.F(1) both had similar frequencies of the F200Y resistant allele (45.3% and 44.3%, respectively), whereas for F167Y, MHco18/3.F(1) had a two-fold greater frequency of the resistant-allele compared to MHco3/18.F(1) (18.2% and 8.8%, respectively). Comparison between pyrosequencing and MiSeq amplicon sequencing revealed that the allele frequencies derived from both methods were concordant at codon 200 (r(c) = 0.97), but were less comparable for codon 167 (r(c) = 0.55). The use of controlled reciprocal genetic crosses have revealed a potential difference in BZ resistance phenotype dependent on whether the resistant allele is paternally or maternally inherited. These findings provide new insight and prompt further investigation into the inheritance of BZ resistance in H. contortus

Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa

The wear of fixed and mobile bearing unicompartmental knee replacements

Unicompartmental knee replacements (UKR) are an option for surgical intervention for the treatment of single-compartment osteoarthritis. The aim of this study was to compare the wear of a low-conformity fixed-bearing UKR with a conforming mobile bearing UKR under two kinematic conditions, to investigate the effect of implant design and kinematics on wear performance in a physiological knee wear simulator. Under both sets of kinematic conditions, the relatively low-conforming fixed UKR showed lower wear, compared with the more conforming anterior-posterior sliding mobile bearing. However, it should be noted that differences in materials between the two designs also contribute to the relative wear performance of the bearings. The combined wear of the medial and lateral bearings of the fixed-bearing UKR as a ‘total knee’ were significantly reduced compared with a fixed-bearing total knee replacement studied under the same kinematic condition

The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury

BACKGROUND: Stromal cell-derived factor 1 (SDF-1 or CXCL12) is chemotaxic for CXCR4 expressing bone marrow-derived cells. It functions in brain embryonic development and in response to ischemic injury in helping guide neuroblast migration and vasculogenesis. In experimental adult stroke models SDF-1 is expressed perivascularly in the injured region up to 30 days after the injury, suggesting it could be a therapeutic target for tissue repair strategies. We hypothesized that SDF-1 would be expressed in similar temporal and spatial patterns following hypoxic-ischemic (HI) injury in neonatal brain. RESULTS: Twenty-five 7-day-old C57BL/J mice underwent HI injury. SDF-1 expression was up regulated up to 7 days after the injury but not at the later time points. The chief sites of SDF-1 up regulation were astrocytes, their foot processes along blood vessels and endothelial cells. CONCLUSION: The localization of SDF-1 along blood vessels in the HI injury zone suggests that these perivascular areas are where chemotaxic signaling for cellular recruitment originates and that reactive astrocytes are major mediators of this process. The associated endothelium is likely to be the site for vascular attachment and diapedesis of CXCR4 receptor expressing cells to enter the injured tissue. Here we show that, relative to adults, neonates have a significantly smaller window of opportunity for SDF-1 based vascular chemotaxic recruitment of bone marrow-derived cells. Therefore, without modification, following neonatal HI injury there is only a narrow period of time for endogenous SDF-1 mediated chemotaxis and recruitment of reparative cells, including exogenously administered stem/progenitor cells

Renewing Criminalized and Hegemonic Cultural Landscapes

The Mafia's long historical pedigree in Mezzogiorno, Southern Italy, has empowered the Mafioso as a notorious, uncontested, and hegemonic figure. The counter-cultural resistance against the mafiosi culture began to be institutionalized in the early 1990s. Today, Libera Terra is the largest civil society organization in the country that uses the lands confiscated from the Mafia as a space of cultural repertoire to realize its ideals. Deploying labor force through volunteer participation, producing biological fruits and vegetables, and providing information to the students on the fields are the principal cultural practices of this struggle. The confiscated lands make the Italian experience of anti-Mafia resistance a unique example by connecting the land with the ideals of cultural change. The sociocultural resistance of Libera Terra conveys a political message through these practices and utters that the Mafia is not invincible. This study draws the complex panorama of the Mafia and anti-Mafia movement that uses the ‘confiscated lands’ as cultural and public spaces for resistance and socio-cultural change. In doing so, this article sheds new light on the relationship between rural criminology and crime prevention policies in Southern Italy by demonstrating how community development practice of Libera Terra changes the meaning of landscape through iconographic symbolism and ethnographic performance

The preparation of large surface area lanthanum based perovskite supports for AuPt nanoparticles: tuning the glycerol oxidation reaction pathway by switching the perovskite B site

Gold and gold alloys, in the form of supported nanoparticles, have been shown over the last three decades to be highly effective oxidation catalysts. Mixed metal oxide perovskites, with their high structural tolerance, are ideal for investigating how changes in the chemical composition of supports affect the catalysts' properties, while retaining similar surface areas, morphologies and metal co-ordinations. However, a significant disadvantage of using perovskites as supports is their high crystallinity and small surface area. We report the use of a supercritical carbon dioxide anti-solvent precipitation methodology to prepare large surface area lanthanum based perovskites, making the deposition of 1 wt% AuPt nanoparticles feasible. These catalysts were used for the selective oxidation of glycerol. By changing the elemental composition of the perovskite B site, we dramatically altered the reaction pathway between a sequential oxidation route to glyceric or tartronic acid and a dehydration reaction pathway to lactic acid. Selectivity profiles were correlated to reported oxygen adsorption capacities of the perovskite supports and also to changes in the AuPt nanoparticle morphologies. Extended time on line analysis using the best oxidation catalyst (AuPt/LaMnO3) produced an exceptionally high tartronic acid yield. LaMnO3 produced from alternative preparation methods was found to have lower activities, but gave comparable selectivity profiles to that produced using the supercritical carbon dioxide anti-solvent precipitation methodology

Trends in mortality by labour market position around retirement ages in three European countries with different welfare regimes

<p>Objectives: In the face of economic downturn and increasing life expectancy, many industrial nations are adopting a policy of postponing the retirement age. However, questions still remain around the consequence of working longer into old age. We examine mortality by work status around retirement ages in countries with different welfare regimes; Finland (social democratic), Turin (Italy; conservative), and England and Wales (liberal).</p> <p>Methods: Death rates and rate ratios (RRs) (reference rates = ‘in-work’), 1970 s–2000 s, were estimated for those aged 45–64 years using the England and Wales longitudinal study, Turin longitudinal study, and the Finnish linked register study.</p> <p>Results: Mortality of the not-in-work was consistently higher than the in-work. Death rates for the not-in-work were lowest in Turin and highest in Finland. Rate ratios were smallest in Turin (RR men 1972–76 1.73; 2002–06 1.63; women 1.22; 1.68) and largest in Finland (RR men 1991–95 3.03; 2001–05 3.80; women 3.62; 4.11). Unlike RRs for men, RRs for women increased in every country (greatest in Finland).</p> <p>Conclusions: These findings signal that overall, employment in later life is associated with lower mortality, regardless of welfare regime.</p&gt

Feasibility of free space quantum key distribution with coherent polarization states

We demonstrate for the first time the feasibility of free space quantum key distribution with continuous variables under real atmospheric conditions. More specifically, we transmit coherent polarization states over a 100m free space channel on the roof of our institute's building. In our scheme, signal and local oscillator are combined in a single spatial mode which auto-compensates atmospheric fluctuations and results in an excellent interference. Furthermore, the local oscillator acts as spatial and spectral filter thus allowing unrestrained daylight operation.Comment: 12 pages, 8 figures, extensions in sections 2, 3.1, 3.2 and 4. This is an author-created, un-copyedited version of an article accepted for publication in New Journal of Physics (Special Issue on Quantum Cryptography: Theory and Practice). IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

Evaluation of vaccine delivery systems for inducing long-lived antibody responses to Dermanyssus gallinae antigen in laying hens

Dermanyssus gallinae, the poultry red mite, is a global threat to the commercial egg-laying industry. Control of D. gallinae is difficult, with only a limited number of effective pesticides and non-chemical treatments available. Here we characterise the candidate vaccine antigen D. gallinae cathepsin D-1 (Dg-CatD-1) and demonstrate that purified refolded recombinant Dg-Cat-D1 (rDg-CatD-1) is an active aspartyl proteinase which digests haemoglobin with a pH optimum of pH 4. Soluble protein extracts from D. gallinae also have haemoglobinase activity, with a pH optimum comparable to the recombinant protein and both proteinase activities were inhibited by the aspartyl proteinase inhibitor Pepstatin A. Enzyme activity and the ubiquitous localization of Dg-CatD-1 protein in sections of adult female mites is consistent with Dg-CatD-1 being a lysosomal proteinase. Using Dg-CatD-1 as a model vaccine antigen, we compared vaccine delivery methods in laying hens via vaccination with: i) purified rDg-CatD-1 with Montanide™ ISA 71 VG adjuvant; ii) recombinant DNA vaccines for expression of rDg-CatD-1 and iii) transgenic coccidial parasite Eimeria tenella expressing rDg-CatD-1. In two independent trials, only birds vaccinated with rDg-CatD-1 with Montanide™ ISA 71 VG produced a strong and long-lasting serum anti-rDg-Cat-D1 IgY response, which was significantly higher than control birds vaccinated with adjuvant only. Furthermore, we showed that egg laying rates of D. gallinae mites fed on birds vaccinated with rDg-CatD-1 in Montanide™ ISA 71 VG was reduced significantly compared with mites fed on unvaccinated birds