Playin’ the city : artistic and scientific approaches to playful urban arts

An Theorien und Diskussionen über die Stadt mangelt es nicht, denn Städte dienen uns u.a. als Projektionsfläche zur Auseinandersetzung mit unserer Vergangenheit, der Gegenwart und unserer Zukunft. Diese Ausgabe 1 (2016) der Navigationen untersucht spielerische Formen dieser Auseinandersetzung in und mit der Stadt durch die sogenannten playful urban arts.The city has been discussed and theorized widely, and it continues to serve as a space in which our sense of the present, past, and future is constantly negotiated. This issue 1 (2016) of Navigationen examines new ways of engaging with cities through what are called the playful urban arts. Playful engagements with the urban environment frequently strive to create new ways of imagining and experiencing the city. In and through play, city spaces can become playgrounds that have the potential to transform people’s sense of themselves as human actors in an urban network of spatially bound and socio-economically grounded actions. Emerging from the playin’siegen urban games festival 2015, the essays and panel discussions assembled in this issue provide an interdisciplinary account of the contemporary playful urban arts. Wiht contributions by Miguel Sicart, Andreas Rauscher, Daniel Stein, Judith Ackermann and Martin Reiche, Michael Straeubig and Sebastian Quack, Marianne Halblaub Miranda and Martin Knöll, and Anne Lena Hartman

Effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with acute hemorrhagic diarrhea

Introduction The impact of probiotics on dogs with acute hemorrhagic diarrhea syndrome (AHDS) has not been evaluated so far. The study aim was to assess the effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with AHDS in a prospective, placebo-controlled, blinded trial. Methods Twenty-five dogs with AHDS with no signs of sepsis were randomly divided into a probiotic (PRO;Visbiome, ExeGi Pharma) and placebo group (PLAC). Treatment was administered for 21 days without antibiotics. Clinical signs were evaluated daily from day 0 to day 8. Key bacterial taxa, C. perfringens encoding NetF toxin and enterotoxin were assessed on days 0, 7, 21. Results Both groups showed a rapid clinical improvement. In PRO a significant clinical recovery was observed on day 3 (p = 0.008), while in PLAC it was observed on day 4 (p = 0.002) compared to day 0. Abundance of Blautia (p<0.001) and Faecalibacterium (p = 0.035) was significantly higher in PRO on day 7 compared to day 0, while in PLAC the abundance of Faecalibacterium was not significantly higher on any study day and Blautia (p = 0.016) was only significantly higher on day 21 compared to day 0. Abundance of C. perfringens was significantly lower on day 7 (p = 0.011) compared to day 0 in PRO but not in PLAC. Enterotoxin genes were significantly lower in PRO on day 21 (p = 0.028) compared to PLAC. Fecal samples of 57% of all dogs were positive for netF toxin genes on day 0 and the abundance was significantly lower on day 7 compared to day 0 in PRO (p = 0.016) and PLAC (p = 0.031). Conclusion The probiotic treatment was associated with an accelerated normalization of the intestinal microbiome. Dogs with aseptic AHDS showed a rapid decrease of netF toxin genes and fast clinical recovery in both groups under symptomatic treatment without antibiotics

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Elucidation of the Sodium - Copper Extrusion Mechanism in CuCrS2\mathrm{CuCrS_{2}}: A High Capacity, Long-Life Anode Material for Sodium-Ion Batteries

The compound CuCrS$_2$ with a quasi‐layered crystal structure was investigated as room temperature rechargeable sodium‐ion battery electrode. It exhibits excellent performance as anode material with a high reversible capacity of 424 mAh g$^{−1}$ at 700 mA g$^{−1}$ after 200 cycles and a capacity retention of 98.6 % compared to the third cycle. Results of ex‐situ X‐Ray diffraction experiments performed at different stages of the discharge process demonstrate that at the beginning of Na uptake, Cu$^+$ cations are reduced to nanosized metallic Cu particles which are expelled from the host lattice. Simultaneously, Na is inserted into the host material leading to the formation of Na$_{0.7}$Cu$_{0.15}$CrS$_2$ with significantly expanded interlayer space. Metallic Cu and Na$_{0.7}$Cu$_{0.15}$CrS$_2$ coexist at this stage of discharge. Increasing the amount of Na per formula unit leads to successive conversion to X‐ray amorphous Cr, nanocrystalline Na$_2$S and metallic Cu. The formation of highly disordered metallic Cr with domain sizes in the range of few nanometres is revealed by atomic pair distribution function analysis. During the charge process, the nanocrystalline Cu particles are retained and Na$_{0.7}$Cu$_{0.15}$CrS$_2$ is at least partially reformed. The finely distributed Cu particles dramatically improve the long‐time stability as evidenced by comparison of the electrochemical behaviour of mere NaCuCrS$_2$