Presenting the Compendium Isotoporum Medii Aevi, a multi-isotope database for Medieval Europe

Here we present the Compendium Isotoporum Medii Aevi (CIMA), an open-access database gathering more than 50,000 isotopic measurements for bioarchaeological samples located within Europe and its margins, and dating between 500 and 1500 CE. This multi-isotope (δ13C, δ15N, δ34S, δ18O, and 87Sr/86Sr) archive of measurements on human, animal, and plant archaeological remains also includes a variety of supporting information that offer, for instance, a taxonomic characterization of the samples, their location, and chronology, in addition to data on social, religious, and political contexts. Such a dataset can be used to identify data gaps for future research and to address multiple research questions, including those related with studies on medieval human lifeways (i.e. human subsistence, spatial mobility), characterization of paleo-environmental and -climatic conditions, and on plant and animal agricultural management practices. Brief examples of such applications are given here and we also discuss how the integration of large volumes of isotopic data with other types of archaeological and historical data can improve our knowledge of medieval Europe.Background & Summary Methods Data Records Technical Validation Usage Note

Anti-neuronal anti-bodies in patients with early psychosis

It may be challenging to distinguish autoimmune encephalitis associated with anti-neuronal autoantibodies from primary psychiatric disorders. Here, serum was drawn from patients with a first-episode psychosis (n = 70) or a clinical high-risk for psychosis (n = 6) and controls (n = 34). We investigated the serum prevalence of 24 antineuronal autoantibodies: IgG antibodies for anti-N-methyl-D-aspartate-type glutamate receptor (anti-NMDAR), glutamate and gamma-aminobutyric acid alpha and beta receptors (GABA-a, GABA-b), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA), glycine receptor (GlyR), metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), contactin-associated protein-like 2 (CASPR2), myelin oligodendrocyte glycoprotein (MOG), glutamic acid decarboxylase-65 (GAD65), collapsin response mediator protein 5/crossveinless-2 (CV2), aquaporin-4 (AQP4), anti-dipeptidyl-peptidase-like protein-6 (DPPX), type 1 anti-neuronal nuclear antibody (ANNA-1, Hu), Ri, Yo, IgLON5, Ma2, zinc finger protein 4 (ZIC4), Rho GTPase-activating protein 26, amphiphysin, and recoverin, as well as IgA and IgM for dopamine-2-receptor (DRD2). Anti-NMDA IgG antibodies were positive with serum titer 1:320 in one patient with a clinical high risk for psychosis. He did not receive a diagnosis of encephalitis after comprehensive neurological evaluation. All other antineuronal autoantibodies were negative and there were no additional findings with immunohistochemistry of brain issues. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Factors predisposing to humoral autoimmunity against brain-antigens in health and disease Analysis of 49 autoantibodies in over 7000 subjects

Background:Circulating autoantibodies (AB) against brain-antigens, often deemed pathological, receive increasing attention. We assessed predispositions and seroprevalence/characteristics of 49 AB in >7000 individuals.Methods:Exploratory cross-sectional cohort study, investigating deeply phenotyped neuropsychiatric patients and healthy individuals of GRAS Data Collection for presence/characteristics of 49 brain-directed serum-AB. Predispositions were evaluated through GWAS of NMDAR1-AB carriers, analyses of immune check-point genotypes, APOE4 status, neurotrauma. Chi-square, Fisher’s exact tests and logistic regression analyses were used.Results:Study of N=7025 subjects (55.8% male; 41±16 years) revealed N=1133 (16.13%) carriers of any AB against 49 defined brain-antigens. Overall, age dependence of seroprevalence (OR=1.018/year; 95% CI [1.015-1.022]) emerged, but no disease association, neither general nor with neuropsychiatric subgroups. Males had higher AB seroprevalence (OR=1.303; 95% CI [1.144-1.486]). Immunoglobulin class (N for IgM:462; IgA:487; IgG:477) and titers were similar. Abundant were NMDAR1-AB (7.7%). Low seroprevalence (1.25%-0.02%) was seen for most AB (e.g. amphiphysin, KCNA2, ARHGAP26, GFAP, CASPR2, MOG, Homer-3, KCNA1, GLRA1b, GAD65). Non-detectable were others. GWAS of NMDAR1-AB carriers revealed three genome-wide significant SNPs, two intergenic, one in TENM3, previously autoimmune disease-associated. Targeted analysis of immune check-point genotypes (CTLA4, PD1, PD-L1) uncovered effects on humoral anti-brain autoimmunity (OR=1.55; 95% CI [1.058-2.271]) and disease likelihood (OR=1.43; 95% CI [1.032-1.985]). APOE4 carriers (∼19%) had lower seropositivity (OR=0.766; 95% CI [0.625-0.933]). Neurotrauma predisposed to NMDAR1-AB seroprevalence (IgM: OR=1.599; 95% CI [1.022-2.468]).Conclusions:Humoral autoimmunity against brain-antigens, frequent across health and disease, is predicted by age, gender, genetic predisposition, and brain injury. Seroprevalence, immunoglobulin class, or titers do not predict disease

Identification of the flotillin-1/2 heterocomplex as a target of autoantibodies in bona fide multiple sclerosis

Background: Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against flotillin in patients with multiple sclerosis (MS). Methods: The target antigen was identified by histo-immunoprecipitation using the patients’ sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis. Correct identification was ascertained by indirect immunofluorescence and neutralization tests using the target antigens recombinantly expressed in HEK293 cells. Results: Serum and CSF of the index patient produced a fine-granular IgG indirect immunofluorescence staining of the hippocampal and cerebellar molecular layers. Flotillin-1 and flotillin-2 were identified as target autoantigens. They also reacted with recombinant human flotillin-1/2 co-expressed in HEK293 cells, but not with the individual flotillins in fixed- and live-cell assays. Moreover, neutralization using flotillin-1/2, but not the single flotillins, abolished the tissue reactivity of patient serum. Screening of 521 patients, for whom anti-aquaporin-4 testing was requested and negative, revealed 8 additional patients with anti-flotillin-1/2 autoantibodies. All eight were negative for anti-MOG. Six patients ex post fulfilled the revised McDonald criteria for MS. Vice versa, screening of 538 MS sera revealed anti-flotillin-1/2 autoantibodies in eight patients. The autoantibodies were not found in a cohort of 67 patients with other neural autoantibody-associated syndromes and in 444 healthy blood donors. Conclusions: Autoantibodies against the flotillin-1/2 heterocomplex, a peripheral membrane protein that is involved in axon outgrowth and regeneration of the optic nerve, are present in 1–2% of patients with bona fide MS

Means versus ends in opaque institutional fields: Trading off compliance and achievement in sustainability standard adoption

__Abstract__ The long-standing discussion on decoupling has recently moved from adopters not implementing the agreed-upon policies to compliant adopters not achieving the goals intended by institutional entrepreneurs. This “means-ends decoupling” prevails especially in highly opaque fields, where practices, causality, and performance are hard to understand and chart. I conceptualize the conditions under which the adoption of institutions in relatively opaque fields leads to the achievement of the envisaged goals. Voluntary sustainability standards governing socioenvironmental issues illustrate these arguments. I argue that the lack of field transparency drives institutional entrepreneurs to create and maintain concrete and uniform rules, apply strong incentives, and disseminate “best practices” to ensure substantive adopter compliance. However, such rigid institutions are ill-equipped to deal with the causal complexity and practice multiplicity underlying opacity while they smother adopter agency. The ensuing tension between substantive compliance and goal achievement leads to an inherent trade-off: institutional entrepreneurs who remedy the policy-practice decoupling may enhance the disparity between means and ends, and vice versa. While sustainability standards and other institutions in highly opaque fields can, therefore, not fully achieve the envisaged goals, the trade-off can be reduced through systemically designed institutions that promote goal internalization and contain niche institutions