Evaluation of recombinant proteins of Neospora caninum as vaccine candidates (in a mouse model)

Abortion, resulting from infections by the parasite Neospora caninum, is a major cause of economic loss to both the dairy and beef industries of cattle-producing countries of the world. Vaccination as a means of preventing abortion and/or infection represents a viable control strategy; indeed a commercial vaccine is available in some countries, albeit of unknown efficacy. The commercial vaccine is based on inactivated tachyzoites of N. caninum but other approaches based on lysates and recombinant antigens of N. caninum may also be feasible. In this study we have used an immunisation/challenge model of transplacental transmission, based on the Qs mouse with an Nc-Liverpool challenge, to investigate the vaccine potential of a number of formulations based on four recombinant proteins of N. caninum (GRA1, GRA2, MIC10, and p24B). All formulations studied were immunogenic in the mouse when assessed by ELISA using sonicated tachyzoite antigen as the target antigen. In one experiment, a mixture of MIC10 and p24B produced partial protection against transplacental transmission of N. caninum in this mouse model; in contrast a live infection of tachyzoites of NC-Nowra given before pregnancy always induces very high levels of protective immunity. The field of vaccines against Neospora-associated abortion in cattle is discussed. © 2008 Elsevier Ltd. All rights reserved

Trends and socioeconomic inequalities in cancer survival in England and Wales up to 2001.

We examined national trends and socioeconomic inequalities in cancer survival in England and Wales during the 1990s, using population-based data on 2.2 million patients who were diagnosed with one of the 20 most common cancers between 1986 and 1999 and followed up to 2001. Patients were assigned to one of five deprivation categories (from 'affluent' to 'deprived') using characteristics of their electoral ward of residence at diagnosis. We estimated relative survival up to 5 years after diagnosis, adjusting separately in each deprivation category for background mortality by age, sex and calendar period. We estimated trends in survival and in the difference in survival between deprivation categories ('deprivation gap') over the periods 1986-90, 1991-95 and 1996-99. We used period analysis to examine likely survival rates in the near future. Survival improved for most cancers in both sexes during the 1990s, and appears likely to continue improving for most cancers in the near future. The deprivation gap in survival between rich and poor was wider for patients diagnosed in the late 1990s than in the late 1980s. Increases in cancer survival in England and Wales during the 1990s are shown to be significantly associated with a widening deprivation gap in survival

5D gravity and the discrepant G measurements

It is shown that 5D Kaluza-Klein theory stabilized by an external bulk scalar field may solve the discrepant laboratory G measurements. This is achieved by an effective coupling between gravitation and the geomagnetic field. Experimental considerations are also addressed.Comment: 13 pages, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The gravitational Constant. Generalized gravitational theories and experiments (30 April-10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, (Kluwer), 13pp. (in print) (2003

Uruk expansion or integrated development? A petrographic and geochemical perspective from Gurga Chiya, Iraqi Kurdistan

The Late Chalcolithic (LC; c.4500-3100BCE) was an important period in the developmental history of ancient Mesopotamia (modern Iraq, north-eastern Syria and south-eastern Turkey). New forms of socio-political and economic organisation are observed, characterised by household/settlement hierarchies, centralised production, craft specialization and redistribution. The Uruk Phenomenon of the latter 4th millennium BCE (LC3-5 in northern Mesopotamia and Middle-Late Uruk Period in southern Mesopotamia) coincides with the world’s first urban societies in northern and southern Mesopotamia. This phenomenon includes the extension of long-distance trade and the spread of material culture (including pottery), architectural elements and administrative devices from southern Iraq across Mesopotamia. Nevertheless, the reasons for the spread of this material culture are a major point of contention in archaeological debate. Within this paper, we apply a combined quantitative and qualitative methods featuring macroscopic observations, ceramic petrography and pXRF to a selection of 38 pottery sherds from Gurga Chiya, a small site located within the Shahrizor Plain, Iraqi Kurdistan. Results demonstrate that the pottery analysed was all locally produced, perhaps at Gurga Chiya itself. Potential reasons for the transmission of the Uruk Phenomenon and its appearance at Gurga Chiya are discussed. We suggest that frequent, low-level contacts between Gurga Chiya and communities of the Shahrizor and adjacent regions as a prospective reason for the transmission of this cultural package into the region

Risk, Unexpected Uncertainty, and Estimation Uncertainty: Bayesian Learning in Unstable Settings

Recently, evidence has emerged that humans approach learning using Bayesian updating rather than (model-free) reinforcement algorithms in a six-arm restless bandit problem. Here, we investigate what this implies for human appreciation of uncertainty. In our task, a Bayesian learner distinguishes three equally salient levels of uncertainty. First, the Bayesian perceives irreducible uncertainty or risk: even knowing the payoff probabilities of a given arm, the outcome remains uncertain. Second, there is (parameter) estimation uncertainty or ambiguity: payoff probabilities are unknown and need to be estimated. Third, the outcome probabilities of the arms change: the sudden jumps are referred to as unexpected uncertainty. We document how the three levels of uncertainty evolved during the course of our experiment and how it affected the learning rate. We then zoom in on estimation uncertainty, which has been suggested to be a driving force in exploration, in spite of evidence of widespread aversion to ambiguity. Our data corroborate the latter. We discuss neural evidence that foreshadowed the ability of humans to distinguish between the three levels of uncertainty. Finally, we investigate the boundaries of human capacity to implement Bayesian learning. We repeat the experiment with different instructions, reflecting varying levels of structural uncertainty. Under this fourth notion of uncertainty, choices were no better explained by Bayesian updating than by (model-free) reinforcement learning. Exit questionnaires revealed that participants remained unaware of the presence of unexpected uncertainty and failed to acquire the right model with which to implement Bayesian updating

Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy