A Marine Reservoir Effect ∆R Value for Kitandach, in Prince Rupert Harbour, British Columbia, Canada

Prince Rupert Harbour (PRH), on the north Pacific Coast of British Columbia, contains at least 157 shell middens, of which 66 are known villages, in an area of approximately 180 km2. These sites span the last 9500 yr and in some cases are immense, exceeding 20,000 m2 surface area and several meters in depth. Recent archaeological research in PRH has become increasingly reliant on radiocarbon dates from marine shell for developing chronologies. However, this is problematic as the local marine reservoir effect (MRE) remains poorly understood in the region. To account for the MRE and to better date the Harbour’s sites, we propose a ΔR of 273±38 for the PRH area, based on our work at the site of Kitandach (GbTo-34), a massive shell midden-village centrally located within the Harbour. We followed the multiple paired sample approach for samples from specific contexts and ensured contemporaneity within the groups of marine and terrestrial materials by statistically assessing for outliers using the χ2 test. Taking together, the results for this and previous studies, it appears the MRE was fairly constant over the past 5000 yr

Variability in North Atlantic marine radiocarbon reservoir effects at c.1000 AD

14C age measurements made on samples from three archaeological sites located on North Atlantic coasts were used to investigate the marine reservoir effect (MRE) at c.1000 AD. This is an important period within human cultural and paleoenvironmental research as it is a time when Norse expansion to the North Atlantic islands occurred, during what appears to be a period of ameliorating climatic conditions. This makes improved chronological precision and accuracy at this time highly desirable. The data indicate a significant latitudinal variation in MRE at c.1000 AD from a ΔR of –152 ± 26 14C yr at Omey Island (530 32’ N) to 57 ± 22 14C yr at Undir Junkarinsfløtti (610 51’ N). The results are compared with modern assessments of MRE values within the context of oceanographic and climatic regimes that provide a possible driving mechanism for spatial and temporal variation in MRE

Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study.

Background/objectivesThe common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD.MethodsFor immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD.ResultsHomozygosity for G at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses.ConclusionsIn sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression

Charcoal production during the Norse and early medieval periods in Eyjafjallahreppur, Southern Iceland

Timber procurement and the use of woodlands is a key issue in the Norse and Medieval period in the North Atlantic islands. This paper outlines evidence for the timing and mechanisms of Norse deforestation in an area of southern Iceland which is tracked through the mapping and analysis of charcoal production pits. Precise dating of the use of these charcoal production pits within a Bayesian framework is demonstrated through the combination of tephrochronology, sediment accumulation rates and multiple radiocarbon dates on the archaeological charcoal. The implications for using charcoal as a dating medium for radiocarbon dating in Iceland and the wider North Atlantic are then explored. Finally, the nature of the deforestation and human impact on the environment is placed into the context of the Norse landnám across the North Atlantic

Future needs and requirements for AMS C-14 standards and reference materials

C-14 measurement uses a number of standards and reference materials with different properties. Historically the absolute calibration of C-14 measurement was tied to 1890 wood, through the 'primary' standard of NBS-OxI (produced by the National Bureau of Standards, now NIST - National Institute of Standards and technology) subsequently replaced by NBS-OxII. These are both internationally calibrated and certified materials, whose C-14 activities are known absolutely. A second tier of materials, often called secondary standards or reference materials, and including internationally recognised materials such as ANU-sucrose (now also IAEA-C6), Chinese - sucrose and the IAEA C1-C6 series, augmented by additional oxalic acid samples are also used routinely. The activity of these materials has been estimated from large numbers of measurements made by many laboratories. Recently, further natural materials from the Third and Fourth International Radiocarbon Inter- comparisons (TIRI and FIRI) have been added to this list. The activities of these standards and reference materials span both the applied C-14 age range and the chemical composition range of typical samples, but this is not achieved uniformly and there is a continuing need for reference materials for laboratory quality control and measurement-traceability purposes. In this paper, we review the development of C-14 Standards and reference materials and consider the future requirements for such materials within the C-14 AMS community

Neuroimaging correlates of brain injury in Wilson's disease: a multimodal, whole-brain MRI study

Wilson's disease is an autosomal-recessive disorder of copper metabolism with neurological and hepatic presentations. Chelation therapy is used to 'de-copper' patients but neurological outcomes remain unpredictable. A range of neuroimaging abnormalities have been described and may provide insights into disease mechanisms, in addition to prognostic and monitoring biomarkers. Previous quantitative MRI analyses have focussed on specific sequences or regions of interest, often stratifying chronically-treated patients according to persisting symptoms as opposed to initial presentation. In this cross-sectional study, we performed a combination of unbiased, whole-brain analyses on T1-weighted, fluid-attenuated inversion recovery, diffusion-weighted and susceptibility-weighted imaging data from 40 prospectively-recruited patients with Wilson's disease (age range 16-68). We compared patients with neurological (n = 23) and hepatic (n = 17) presentations to determine the neuroradiological sequelae of the initial brain injury. We also subcategorized patients according to recent neurological status, classifying those with neurological presentations or deterioration in the preceding six months as having 'active' disease. This allowed us to compare patients with active (n = 5) and stable (n = 35) disease and identify imaging correlates for persistent neurological deficits and copper indices in chronically-treated, stable patients. Using a combination of voxel-based morphometry and region-of-interest volumetric analyses, we demonstrate that grey matter volumes are lower in the basal ganglia, thalamus, brainstem, cerebellum, anterior insula and orbitofrontal cortex when comparing patients with neurological and hepatic presentations. In chronically-treated, stable patients, the severity of neurological deficits correlated with grey matter volumes in similar, predominantly subcortical regions. In contrast, the severity of neurological deficits did not correlate with the volume of white matter hyperintensities, calculated using an automated lesion segmentation algorithm. Using tract-based spatial statistics, increasing neurological severity in chronically-treated patients was associated with decreasing axial diffusivity in white matter tracts whereas increasing serum non-caeruloplasmin-bound ('free') copper and active disease were associated with distinct patterns of increasing mean, axial and radial diffusivity. Whole-brain quantitative susceptibility mapping identified increased iron deposition in the putamen, cingulate and medial frontal cortices of patients with neurological presentations relative to those with hepatic presentations and neurological severity was associated with iron deposition in widespread cortical regions in chronically-treated patients. Our data indicate that composite measures of subcortical atrophy provide useful prognostic biomarkers, whereas abnormal mean, axial and radial diffusivity are promising monitoring biomarkers. Finally, deposition of brain iron in response to copper accumulation may directly contribute to neurodegeneration in Wilson's disease

Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE

Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

Nuclear reprocessing-related radiocarbon (¹⁴C) uptake in UK marine mammals

To evaluate the transfer of Sellafield-derived radiocarbon (14C) to top predators in the UK marine environment, 14C activities were examined in stranded marine mammals. All samples of harbour porpoise (Phocoena phocoena) obtained from the Irish Sea showed 14C enrichment above background. Mammal samples obtained from the West of Scotland, including harbour porpoise, grey seals (Halichoerus grypus) and harbour seals (Phoca vitulina) showed 14C enrichment but to a lesser extent. This study demonstrates, for the first time, enriched 14C is transferred through the marine food web to apex predators as a consequence of ongoing nuclear reprocessing activities at Sellafield. Total Sellafield 14C discharge activity 24 months prior to stranding and, in particular, distance of animal stranding site from Sellafield are significant variables affecting individual 14C activity. 14C activities of West of Scotland harbour porpoises suggest they did not forage in the Irish Sea prior to stranding, indicating a high foraging fidelity

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis