Fish for the city: meta-analysis of archaeological cod remains and the growth of London's northern trade

The growth of medieval cities in Northern Europe placed new demands on food supply, and led to the import of fish from increasingly distant fishing grounds. Quantitative analysis of cod remains from London provides revealing insight into the changing patterns of supply that can be related to known historical events and circumstances. In particular it identifies a marked increase in imported cod from the thirteenth century AD. That trend continued into the fifteenth and sixteenth centuries, after a short downturn, perhaps attributable to the impact of the Black Death, in the mid fourteenth century. The detailed pattern of fluctuating abundance illustrates the potential of archaeological information that is now available from the high-quality urban excavations conducted in London and similar centres during recent decades

Stable isotope evidence for late medieval (14th-15th C) origins of the eastern Baltic cod (Gadus morhua) fishery

Although recent historical ecology studies have extended quantitative knowledge of eastern Baltic cod (Gadus morhua) exploitation back as far as the 16th century, the historical origin of the modern fishery remains obscure. Widespread archaeological evidence for cod consumption around the eastern Baltic littoral emerges around the 13th century, three centuries before systematic documentation, but it is not clear whether this represents (1) development of a substantial eastern Baltic cod fishery, or (2) large-scale importation of preserved cod from elsewhere. To distinguish between these hypotheses we use stable carbon and nitrogen isotope analysis to determine likely catch regions of 74 cod vertebrae and cleithra from 19 Baltic archaeological sites dated from the 8th to the 16th centuries. δ¹³C and δ¹⁵N signatures for six possible catch regions were established using a larger sample of archaeological cod cranial bones (n = 249). The data strongly support the second hypothesis, revealing widespread importation of cod during the 13th to 14th centuries, most of it probably from Arctic Norway. By the 15th century, however, eastern Baltic cod dominate within our sample, indicating the development of a substantial late medieval fishery. Potential human impact on cod stocks in the eastern Baltic must thus be taken into account for at least the last 600 years.The research was funded by the Leverhulme Trust (grant no. F/00 224/S), the History of Marine Animal Populations project (supported by the Alfred P. Sloan Foundation) and the McDonald Institute for Archaeological Research

Repeatability of IVIM biomarkers from diffusion-weighted MRI in head and neck:Bayesian probability versus neural network

Purpose: The intravoxel incoherent motion (IVIM) model for DWI might provide useful biomarkers for disease management in head and neck cancer. This study compared the repeatability of three IVIM fitting methods to the conventional nonlinear least-squares regression: Bayesian probability estimation, a recently introduced neural network approach, IVIM-NET, and a version of the neural network modified to increase consistency, IVIM-NETmod. Methods: Ten healthy volunteers underwent two imaging sessions of the neck, two weeks apart, with two DWI acquisitions per session. Model parameters (ADC, diffusion coefficient (Formula presented.), perfusion fraction (Formula presented.), and pseudo-diffusion coefficient (Formula presented.)) from each fit method were determined in the tonsils and in the pterygoid muscles. Within-subject coefficients of variation (wCV) were calculated to assess repeatability. Training of the neural network was repeated 100 times with random initialization to investigate consistency, quantified by the coefficient of variance. Results: The Bayesian and neural network approaches outperformed nonlinear regression in terms of wCV. Intersession wCV of (Formula presented.) in the tonsils was 23.4% for nonlinear regression, 9.7% for Bayesian estimation, 9.4% for IVIM-NET, and 11.2% for IVIM-NETmod. However, results from repeated training of the neural network on the same data set showed differences in parameter estimates: The coefficient of variances over the 100 repetitions for IVIM-NET were 15% for both (Formula presented.) and (Formula presented.), and 94% for (Formula presented.); for IVIM-NETmod, these values improved to 5%, 9%, and 62%, respectively. Conclusion: Repeatabilities from the Bayesian and neural network approaches are superior to that of nonlinear regression for estimating IVIM parameters in the head and neck

Supramolecular heterostructures formed by sequential epitaxial deposition of two-dimensional hydrogen-bonded arrays

Two-dimensional (2D) supramolecular arrays provide a route to the spatial control of the chemical functionality of a surface, but their deposition is in almost all cases limited to a monolayer termination. Here we investigated the sequential deposition of one 2D array on another to form a supramolecular heterostructure and realize the growth—normal to the underlying substrate—of distinct ordered layers, each of which is stabilized by in-plane hydrogen bonding. For heterostructures formed by depositing terephthalic acid or trimesic acid on cyanuric acid/melamine, we have determined, using atomic force microscopy under ambient conditions, a clear epitaxial arrangement despite the intrinsically distinct symmetries and/or lattice constants of each layer. Structures calculated using classical molecular dynamics are in excellent agreement with the orientation, registry and dimensions of the epitaxial layers. Calculations confirm that van der Waals interactions provide the dominant contribution to the adsorption energy and registry of the layers

Analysis of renal diffusion-weighted imaging (DWI) using apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) models

Analysis of renal diffusion-weighted imaging (DWI) data to derive markers of tissue properties requires careful consideration of the type, extent, and limitations of the acquired data. Alongside data quality and general suitability for quantitative analysis, choice of diffusion model, fitting algorithm, and processing steps can have consequences for the precision, accuracy, and reliability of derived diffusion parameters. Here we introduce and discuss important steps for diffusion-weighted image processing, and in particular give example analysis protocols and pseudo-code for analysis using the apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) models. Following an overview of general principles, we provide details of optional steps, and steps for validation of results. Illustrative examples are provided, together with extensive notes discussing wider context of individual steps, and notes on potential pitfalls.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concepts and experimental procedure

Expression of the Multiple Sclerosis-Associated MHC Class II Allele HLA-DRB1*1501 Is Regulated by Vitamin D

Multiple sclerosis (MS) is a complex trait in which allelic variation in the MHC class II region exerts the single strongest effect on genetic risk. Epidemiological data in MS provide strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of this disease. Growing evidence implicates sunlight or vitamin D as a key environmental factor in aetiology. We hypothesised that this environmental candidate might interact with inherited factors and sought responsive regulatory elements in the MHC class II region. Sequence analysis localised a single MHC vitamin D response element (VDRE) to the promoter region of HLA-DRB1. Sequencing of this promoter in greater than 1,000 chromosomes from HLA-DRB1 homozygotes showed absolute conservation of this putative VDRE on HLA-DRB1*15 haplotypes. In contrast, there was striking variation among non–MS-associated haplotypes. Electrophoretic mobility shift assays showed specific recruitment of vitamin D receptor to the VDRE in the HLA-DRB1*15 promoter, confirmed by chromatin immunoprecipitation experiments using lymphoblastoid cells homozygous for HLA-DRB1*15. Transient transfection using a luciferase reporter assay showed a functional role for this VDRE. B cells transiently transfected with the HLA-DRB1*15 gene promoter showed increased expression on stimulation with 1,25-dihydroxyvitamin D3 (P = 0.002) that was lost both on deletion of the VDRE or with the homologous “VDRE” sequence found in non–MS-associated HLA-DRB1 haplotypes. Flow cytometric analysis showed a specific increase in the cell surface expression of HLA-DRB1 upon addition of vitamin D only in HLA-DRB1*15 bearing lymphoblastoid cells. This study further implicates vitamin D as a strong environmental candidate in MS by demonstrating direct functional interaction with the major locus determining genetic susceptibility. These findings support a connection between the main epidemiological and genetic features of this disease with major practical implications for studies of disease mechanism and prevention

Prezygotic Barriers to Hybridization in Marine Broadcast Spawners: Reproductive Timing and Mating System Variation

Sympatric assemblages of congeners with incomplete reproductive barriers offer the opportunity to study the roles that ecological and non-ecological factors play in reproductive isolation. While interspecific asynchrony in gamete release and gametic incompatibility are known prezygotic barriers to hybridization, the role of mating system variation has been emphasized in plants. Reproductive isolation between the sibling brown algal species Fucus spiralis, Fucus guiryi (selfing hermaphrodite) and Fucus vesiculosus (dioecious) was studied because they form hybrids in parapatry in the rocky intertidal zone, maintain species integrity over a broad geographic range, and have contrasting mating systems. We compared reproductive synchrony (spawning overlap) between the three species at several temporal scales (yearly/seasonal, semilunar/tidal, and hourly during single tides). Interspecific patterns of egg release were coincident at seasonal (single peak in spring to early summer) to semilunar timescales. Synthesis of available data indicated that spawning is controlled by semidiurnal tidal and daily light-dark cues, and not directly by semilunar cycles. Importantly, interspecific shifts in timing detected at the hourly scale during single tides were consistent with a partial ecological prezygotic hybridization barrier. The species displayed patterns of gamete release consistent with a power law distribution, indicating a high degree of reproductive synchrony, while the hypothesis of weaker selective constraints for synchrony in selfing versus outcrossing species was supported by observed spawning in hermaphrodites over a broader range of tidal phase than in outcrossers. Synchronous gamete release is critical to the success of external fertilization, while high-energy intertidal environments may offer only limited windows of reproductive opportunity. Within these windows, however, subtle variations in reproductive timing have evolved with the potential to form ecological barriers to hybridization

Historical Demographic Processes Dominate Genetic Variation in Ancient Atlantic Cod Mitogenomes

Ancient DNA (aDNA) approaches have been successfully used to infer the long-term impacts of climate change, domestication, and human exploitation in a range of terrestrial species. Nonetheless, studies investigating such impacts using aDNA in marine species are rare. Atlantic cod (Gadus morhua), is an economically important species that has experienced dramatic census population declines during the last century. Here, we investigated 48 ancient mitogenomes from historical specimens obtained from a range of archeological excavations in northern Europe dated up to 6,500 BCE. We compare these mitogenomes to those of 496 modern conspecifics sampled across the North Atlantic Ocean and adjacent seas. Our results confirm earlier observations of high levels of mitogenomic variation and a lack of mutation-drift equilibrium—suggestive of population expansion. Furthermore, our temporal comparison yields no evidence of measurable mitogenomic changes through time. Instead, our results indicate that mitogenomic variation in Atlantic cod reflects past demographic processes driven by major historical events (such as oscillations in sea level) and subsequent gene flow rather than contemporary fluctuations in stock abundance. Our results indicate that historical and contemporaneous anthropogenic pressures such as commercial fisheries have had little impact on mitogenomic diversity in a wide-spread marine species with high gene flow such as Atlantic cod. These observations do not contradict evidence that overfishing has had negative consequences for the abundance of Atlantic cod and the importance of genetic variation in implementing conservation strategies. Instead, these observations imply that any measures toward the demographic recovery of Atlantic cod in the eastern Atlantic, will not be constrained by recent loss of historical mitogenomic variation.</jats:p

The Causal Cascade to Multiple Sclerosis: A Model for MS Pathogenesis

BACKGROUND: MS pathogenesis seems to involve both genetic susceptibility and environmental risk factors. Three sequential factors are implicated in the environmental risk. The first acts near birth, the second acts during childhood, and the third acts long thereafter. Two candidate factors (vitamin D deficiency and Epstein-Barr viral infection) seem well suited to the first two environmental events. METHODOLOGY/PRINCIPAL FINDINGS: A mathematical Model for MS pathogenesis is developed, incorporating these environmental and genetic factors into a causal scheme that can explain some of the recent changes in MS-epidemiology (e.g., increasing disease prevalence, a changing sex-ratio, and regional variations in monozygotic twin concordance rates). CONCLUSIONS/SIGNIFICANCE: This Model suggests that genetic susceptibility is overwhelmingly the most important determinant of MS pathogenesis. Indeed, over 99% of individuals seem genetically incapable of developing MS, regardless of what environmental exposures they experience. Nevertheless, the contribution of specific genes to MS-susceptibility seems only modest. Thus, despite HLA DRB1*1501 being the most consistently identified genetic marker of MS-susceptibility (being present in over 50% of northern MS patient populations), only about 1% of individuals with this allele are even genetically susceptible to getting MS. Moreover, because genetic susceptibility seems so similar throughout North America and Europe, environmental differences principally determine the regional variations in disease characteristics. Additionally, despite 75% of MS-patients being women, men are 60% more likely to be genetically-susceptible than women. Also, men develop MS at lower levels of environmental exposure than women. Nevertheless, women are more responsive to the recent changes in environmental-exposure (whatever these have been). This explains both the changing sex-ratio and the increasing disease prevalence (which has increased by a minimum of 32% in Canada over the past 35 years). As noted, environmental risk seems to result from three sequential components of environmental exposure. The potential importance of this Model for MS pathogenesis is that, if correct, a therapeutic strategy, designed to interrupt one or more of these sequential factors, has the potential to markedly reduce or eliminate disease prevalence in the future