The human prion protein residue 129 polymorphism lies within a cluster of epitopes for T cell recognition.

T cell immune responses to central nervous system-derived and other self-antigens are commonly described in both healthy and autoimmune individuals. However, in the case of the human prion protein (PrP), it has been argued that immunologic tolerance is uncommonly robust. Although development of an effective vaccine for prion disease requires breaking of tolerance to PrP, the extent of immune tolerance to PrP and the identity of immunodominant regions of the protein have not previously been determined in humans. We analyzed PrP T cell epitopes both by using a predictive algorithm and by measuring functional immune responses from healthy donors. Interestingly, clusters of epitopes were focused around the area of the polymorphic residue 129, previously identified as an indicator of susceptibility to prion disease, and in the C-terminal region. Moreover, responses were seen to PrP peptide 121-134 containing methionine at position 129, whereas PrP 121-134 [129V] was not immunogenic. The residue 129 polymorphism was also associated with distinct patterns of cytokine response: PrP 128-141 [129M] inducing IL-4 and IL-6 production, which was not seen in response to PrP 128-141 [129V]. Our data suggest that the immunogenic regions of human PrP lie between residue 107 and the C-terminus and that, like with many other central nervous system antigens, healthy individuals carry responses to PrP within the T cell repertoire and yet do not experience deleterious autoimmune reactions.

Cinderella comes to the Ball: Article 14 and the right to non-discrimination in the ECHR

Article 14 ECHR has often been derided as a Cinderella provision, but during the last few years, this has started to change. This article examines how Article 14 has developed, and may live up to its potential as a powerful non-discrimination principle. The case law developments in relation to the “ambit” requirement in Article 14, the development of indirect discrimination case law, and the approval of positive action, all point to a more substantive conception of equality, which offers protection to disadvantaged and vulnerable groups.

Journal article: Children and Religion under Article 14 UNCRC: A Critical Analysis

This article examines the text of Article 14 of the UN Convention on the Rights of the Child 1989 and the work of the UN Committee on the Rights of the Child. It considers the text of the article and its travaux préparatoires; it then provides an analysis of the issues considered by the Committee: the concept of the evolving capacities of the child, freedom of religious choice, freedom of manifestation, and education. It also highlights the problems that have emerged in the Committee’s work, in the light of a theoretical framework of the right of the child to religious freedom in international law. It concludes that the Committee fails children in relation to their religion and suggests some positive steps to be taken by the Committee.

SRIF receptor subtype expression and involvement in positive and negative contractile effects of somatostatin-14 (SRIF-14) in ventricular cardiomyocytes.

Background/Aims: Somatostatin-14 (SRIF-14), a neuropeptide co-stored with acetylcholine in the cardiac parasympathetic innervation, exerts both positive and negative influences directly on contraction of ventricular cardiomyocytes, indicative of involvement of more than one of five known SRIF (SSTR) receptor subtypes. The aim was to characterize receptor subtype expression in adult rat ventricular cardiomyocytes and to investigate the influence of a series of SRIF (SSTR) subtype-selective agonists on contractile parameters. Methods: mRNA and protein expression of each receptor subtype were quantified by RT-PCR and immunoblotting respectively; for contraction studies, cells were stimulated at 0.5 Hz under basal conditions and in the presence of isoprenaline (ISO, 10-8M). Results: all five SRIF (SSTR) receptor subtypes were expressed in cardiomyocytes although SRIF1A (SSTR2) and SRIF2A (SSTR1) were less abundant than the other subtypes. L803087 (10-8M), a SRIF2B (SSTR4) agonist, attenuated ISO-stimulated peak contractile amplitude and prolonged relaxation time (T50). L796778 (10-7M), a SRIF1C (SSTR3) agonist, augmented basal and ISO-stimulated peak contractile amplitude; L779976 (10-8M) and L817818 (10-9M), agonists at SRIF1A (SSTR2) and SRIF1B (SSTR5) receptors, respectively, also augmented ISO-stimulated peak amplitude. Conclusion: these data support involvement of SRIF2B (SSTR4) receptors in the negative contractile effects of SRIF-14, while one or more of the three SRIF1 receptor subtypes (SSTR2, 3 or 5) may contribute to the positive contractile effects of SRIF-14.

Radiocarbon wiggle-match dating of proglacial lake sediments - Implications for the 8.2 ka event

The problem of insufficient age-control limits the utilisation of the 8.2 ka BP event for modelling freshwater forcing in climate change studies. High-resolution radiocarbon dates, magnetic susceptibility and lithostratigraphic evidence from a lake sediment core from Nedre Hervavatnet located at Sygnefjell in western Norway provide a record of the early Holocene. We use the method of radiocarbon wiggle-match dating of the lake sediments using the non-linear relationship between the C-14 calibration curve and the consecutive accumulation order of the sample series in order to build a high-resolution age-model. The timing and duration of Holocene environmental changes is estimated using 38 AMS radiocarbon dates on terrestrial macrofossils, insects and chironomids covering the time period from 9750 to 1180 cal BP. Chironomids, Salix and Betula leaves produce the most consistent results. Sedimentological and physical properties of the core suggest that three meltwater events with high sedimentation rates are superimposed on a long-term trend with glacier retreat between 9750 and 8000 cal BP. The lake sediment sequence of Nedre Hervavatnet demonstrates the following: only a reliable high-resolution geochronology based on carefully selected terrestrial macrofossils allows the reconstruction of a more refined and complex environmental change history before and during the 8.2 ka event. (C) 2009 Elsevier Ltd. All rights reserved.

Cooling and changing seasonality in the Southern Alps, New Zealand during the Antarctic Cold Reversal

A comprehensively C-14 AMS dated pollen and chironomid record from Boundary Stream Tarn provides the first chironomid-derived temperature reconstruction to quantify temperature change during Lateglacial times (17,500-10,000 cal yr BP) in the Southern Alps, New Zealand. The records indicate a ca 1000-year disruption to the Lateglacial warming trend and an overall cooling consistent with the Antarctic Cold Reversal (ACR). The main interval of chironomid-inferred summer temperature depression (similar to 2-3 degrees C) lasted about 700 years during the ACR. Following this cooling event, both proxies indicate a warming step to temperatures slightly cooler than present during the Younger Dryas chronozone (12,900-11,500 cal yr BP). These results highlight a direct linkage between Antarctica and mid-latitude terrestrial climate systems and the largely asynchronous nature of the interhemispheric climate system during the last glacial transition. The greater magnitude of temperature changes shown by the chironomid record is attributed to the response of the proxies to differences in seasonal climate with chironomids reflecting summer temperature and vegetation more strongly controlled by duration of winter or by minimum temperatures. These differences imply stronger seasonality at times during the Lateglacial, which may explain some of the variability between other paleoclimate records from New Zealand and have wider implications for understanding differences between proxy records for abrupt climate change. (C) 2007 Elsevier Ltd. All rights reserved.

High precision C-14 dating of Holocene peat deposits: A comparison of Bayesian calibration and wiggle-matching approaches

The chronologies of five northern European ombrotrophic peat bogs subjected to a large ANIS C-14 dating effort (32-44 dates/site) are presented here. The results of Bayesian calibration (BCal) of dates with a prior assumption of chronological ordering were compared with a Bayesian wiggle-match approach (Bpeat) which assumes constant linear accumulation over sections of the peat profile. Interpolation of BCal age estimates of dense sequences of C-14 dates showed variable patterns of peat accumulation with time, with changes in accumulation occurring at intervals ranging from 20 to 50 cm. Within these intervals, peat accumulation appeared to be relatively linear. Close analysis suggests that some of the inferred variations in accumulation rate were related to the plant macrofossil composition of the peat. The wiggle-matched age-depth models had relatively high chronological uncertainty within intervals of closely spaced 14 C dates, suggesting that the premise of constant linear accumulation over large sections of the peat profile is unrealistic. Age models based on the assumption of linear accumulation over large parts of a peat core (and therefore only effective over millennial timescales), are not compatible with studies examining environmental change during the Holocene, where variability often occurs at decadal to centennial time-scales. Ideally, future wiggle-match age models should be constrained, with boundaries between sections based on the plant macrofossil composition of the peat and physical-chemical parameters such as the degree of decomposition. Strategies for the selection of material for dating should be designed so that there should be enough C-14 dates to accurately reconstruct the peat accumulation rate of each homogeneous stratigraphic unit. (c) 2006 Elsevier Ltd. All rights reserved.

Peat multi-proxy data from Mannikjarve bog as indicators of late Holocene climate changes in Estonia

As part of a wider project on European climate change over the past 4500 years, a 4.5-m peat core was taken from a lawn microform on Mannikjarve bog, Estonia. Several methods were used to yield proxy-climate data: (i) a quadrat and leaf-count method for plant macrofossil data, (ii) testate amoebae analysis, and (iii) colorimetric determination of peat humification. These data are provided with an exceptionally high resolution and precise chronology. Changes in bog surface wetness were inferred using Detrended Correspondence Analysis (DCA) and zonation of macrofossil data, particularly concerning the occurrence of Sphagnum balticum, and a transfer function for water-table depth for testate amoebae data. Based on the results, periods of high bog surface wetness appear to have occurred at c. 3100, 3010-2990, 2300, 1750-1610, 1510, 14 10, 1110, 540 and 3 10 cal. yr BP, during four longer periods between c. 3170 and 2850 cal. yr BP, 2450 and 2000 cal. yr BP, 1770 and 1530 cal. yr BP and in the period from 880 cal. yr BP until the present. In the period between 1770 and 1530 cal. yr BP. the extension or initiation of a hollow microtope occurred, which corresponds with other research results from Mannikjarve bog. This and other changes towards increasing bog surface wetness may be the responses to colder temperatures and the predominance of a more continental climate in the region, which favoured the development of bog microdepressions and a complex bog microtopography. Located in the border zone of oceanic and continental climatic sectors, in an area almost without land uplift, this study site may provide valuable information about changes in palaeohydrological and palaeoclimatological conditions in the northern parts of the eastern Baltic Sea region.

Patterns of variation at a mitochondrial sequence-tagged-site locus provides new insights into the postglacial history of European Pinus sylvestris populations

Due to their maternal mode of inheritance, mitochondrial markers can be regarded as almost 'ideal' tools in evolutionary studies of conifer populations. In the present study, polymorphism was analysed at one mitochondrial intron (nad 1, exon B/C) in 23 native European Pinus sylvestris populations. In a preliminary screening for variation using a polymerase chain reaction-restriction fragment length polymorphism approach, two length variants were identified. By fully sequencing the 2.5 kb region, the observed length polymorphism was found to result from the insertion of a 31 bp sequence, with no other mutations observed within the intron. A set of primers was designed flanking the observed mutation, which identified a novel sequence-tagged-site mitochondrial marker for P. sylvestris. Analysis of 747 trees from the 23 populations using these primers revealed the occurrence of two distinct haplotypes in Europe. Within the Iberian Peninsula, the two haplotypes exhibited extensive population differentiation (Phi(ST) = 0.59; P less than or equal to 0.001) and a marked geographical structuring. In the populations of central and northern Europe, one haplotype largely predominated, with the second being found in only one individual of one population.