18 research outputs found

    Das Ländliche als kulturelle Kategorie: aktuelle kulturwissenschaftliche Perspektiven auf Stadt-Land-Beziehungen

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    Das Ländliche hat Konjunktur. Zwischen medialer »Landlust« und realem Strukturwandel in den ländlichen Räumen Europas differenziert es sich dynamisch aus. Idylle oder Problemregion? Arbeitsort oder Freizeitpark? Repräsentationen und lebensweltliche Erfahrungen des Ländlichen avancieren zu einem alltagskulturellen Konfliktfeld, auf dem sich vor einem historischen Hintergrund elementare Problemlagen der Gegenwart und die Komplexität von kulturellen Land-Stadt-Beziehungen spiegeln.Die Beiträge des Bandes liefern hierzu Einsichten aus der Forschungsperspektive der Europäischen Ethnologie und rahmen das Thema damit für historische und gegenwartsbezogene Kulturanalysen begrifflich, methodisch und theoretisch

    The Effect of Micrococcal Nuclease Digestion on Nucleosome Positioning Data

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    Eukaryotic genomes are packed into chromatin, whose basic repeating unit is the nucleosome. Nucleosome positioning is a widely researched area. A common experimental procedure to determine nucleosome positions involves the use of micrococcal nuclease (MNase). Here, we show that the cutting preference of MNase in combination with size selection generates a sequence-dependent bias in the resulting fragments. This strongly affects nucleosome positioning data and especially sequence-dependent models for nucleosome positioning. As a consequence we see a need to re-evaluate whether the DNA sequence is a major determinant of nucleosome positioning in vivo. More generally, our results show that data generated after MNase digestion of chromatin requires a matched control experiment in order to determine nucleosome positions

    Analysis of shared heritability in common disorders of the brain

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    ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

    The genetic architecture of the human cerebral cortex

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    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

    Silver Nanoparticles in the Lung: Toxic Effects and Focal Accumulation of Silver in Remote Organs

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    The distribution of silver (Ag) into remote organs secondary to the application of Ag nanoparticles (Ag-NP) to the lung is still incompletely understood and was investigated in the rat with imaging methods. Dose-finding experiments were carried out with 50 nm- or 200 nm-sized polyvinyl pyrrolidine (PVP)-coated Ag-NP using alveolar macrophages in vitro and female rats, which received Ag-NP via intratracheal instillation. In the main study, we administered 37.5–300 µg per rat lung of the more toxic Ag50-PVP and assessed the broncho-alveolar lavage fluid (BALF) for inflammatory cells, total protein and fibronectin after three and 21 days. In parallel, lung tissue was analysed for DNA double-strand breaks and altered cell proliferation. While 75–150 µg Ag50-PVP per rat lung caused a reversible inflammation, 300 µg led to DNA damage, accelerated cell proliferation and progressively increasing numbers of neutrophilic granulocytes. Ag accumulation was significant in homogenates of liver and other peripheral organs upon lung dose of ≥75 µg. Quantitative laser-ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) combined with enhanced dark field microscopy and autometallography revealed focal accumulations of Ag and/or Ag-NP in sections of peripheral organs: mediastinal lymph nodes contained Ag-NP especially in peripheral macrophages and Ag in argyrophilic fibres. In the kidney, Ag had accumulated within proximal tubuli, while renal filter structures contained no Ag. Discrete localizations were also observed in immune cells of liver and spleen. Overall, the study shows that concentrations of Ag-NP, which elicit a transient inflammation in the rat lung, lead to focal accumulations of Ag in peripheral organs, and this might pose a risk to particular cell populations in remote sites

    Clinical characterisation of women with persistent genital arousal disorder: the iPGAD-study

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    Abstract Persistent Genital Arousal Disorder (PGAD) is a rare condition—mostly in women—where patients perceive prolonged genital arousal without any sexual desire or stimulation. Etiopathological considerations reach from peripheral to central issues over local disturbance of the pudendal nerve to neuropathy, psychosocial, and pharmacological theories. Since well controlled clinical studies about PGAD in conjunction with a mental and somatic health status are missing, this study is a detailed clinical investigation of PGAD patients compared to healthy controls. 26 women who fulfilled diagnostic criteria for PGAD were compared to 26 age matched healthy controls. Investigations included comparison of vegetative, gynaecological and sexual history, psychiatric features as well as a (neuro-)radiological, neurophysiological and gynaecological examination. Moreover, a detailed clinical characterisation of PGAD symptoms was performed. PGAD symptoms were mostly characterised as tingling or prickling and were permanently present. In over 80%, PGAD symptoms were located in the clitoris. Almost 70% reported radiations to other regions of the body. Most frequent trigger factors were tight clothes, mental stress, driving a car/bus/bicycle and sexual intercourse. Relieving factors were mainly distraction, relaxation, physical exercise, masturbation and swimming. In group comparisons, PGAD presented with significant higher rates of sexual dysfunctions, spontaneous orgasms, swelling of the genitals, extraordinary lubrication as well as higher rates in depression, agoraphobia, generalized anxiety disorder and lifetime panic disorder. Significantly more PGAD patients were diagnosed with restless legs symptoms. In contrast childhood traumatization, somatization disorder, suicidality, gynaecological as well as neurophysiological examination of the pudendal nerve were not different between the groups. MRI of the brain, pelvis and spinal cord was unsuspicious and incidental findings - including Tarlov cysts or pelvic venous congestion - were equally distributed among the groups. In summary, our study provides a careful characterization of women with PGAD highlighting a serious mental burden, most probably as a consequence of PGAD. With the current set of clinical investigations there was no evidence of a clear causal relationship to a specific clinical finding as it has been previously discussed. Future studies and additional techniques will have to further explore where and how in the peripheral or central nervous systems PGAD develops

    Nucleosome positioning in the Gal1-10 Locus.

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    <p>Shown is the Gal1-10 locus on chromosome II (277,554 to 279500). The blue boxes mark the open reading frames of annotated genes, where the direction of the arrowheads correspond to the direction of transcription. The transcription factor binding sites are from Harbison <i>et al.</i> (2004) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015754#pone.0015754-Harbison1" target="_blank">[45]</a>. The DNAse I tag numbers are from Hesselberth <i>et al.</i> (2009) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015754#pone.0015754-Hesselberth1" target="_blank">[42]</a>, shown on the y axis is the number of tags for each position. Nucleosome positions determined by Li and Smerdon (2002) are denoted as black boxes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015754#pone.0015754-Li1" target="_blank">[40]</a>. The profiles of the <i>in vivo</i> (blue), <i>in vitro</i> (green) and the MNase digestion of naked DNA (gray) are shown underneath. The y axes of these profiles correspond to the nucleosome occupancy/coverage per base pair normalized by dividing by the genome wide average. The dashed line at 1.0 therefore corresponds therefore to the genome wide average. The last track shows the GC-content (black) in percent in 147 base pair windows centered around the central base pair. The gray box denotes the UAS of Gal1 and Gal10.</p

    Comparison of the average genome wide relative coverage of sequence of length 5.

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    <p>(<b>A</b>) the MNase generated map on naked DNA (<i>x</i> axis) and the <i>in vitro</i> reconstituted nucleosome map (<i>y axis</i>); (<b>B</b>) the MNase generated map on naked DNA (<i>x</i> axis) and the <i>in vivo</i> (YPD) nucleosome map (<i>y axis</i>); (<b>C</b>) the <i>in vivo</i> (YPD) nucleosome map (<i>x axis</i>) and the <i>in vitro</i> nucleosome map (<i>y axis</i>). The Pearson correlation coefficients <i>r</i> between the data sets are indicated.</p

    MNase digestion leads to systematic measurement bias.

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    <p>(<b>A</b>–<b>C</b>) Density plot comparison between the normalized coverage per base pair in the MNase generated map on naked DNA (<i>x</i> axis) and (<b>A</b>) the <i>in vitro</i> reconstituted, (<b>B</b>) the <i>in vivo</i> (YPD) and (<b>C</b>) the predicted nucleosome map (<i>y</i> axis). The color of each point represents the density of base pairs mapping to it, where the density-color relationship is shown at the right of each plot. The Pearson correlation coefficients <i>r</i> between the data sets are indicated. (<b>D</b>) The GC-content profile in percent (3 base pair moving average) around the start coordinate of the reads. The gray filled curve corresponds to the profile obtained by digesting naked DNA with MNase and the blue and green curve represent the profile for the <i>in vitro</i> and <i>in vivo</i> (YPD) data, respectively. The dashed horizontal line indicates the average GC content in the yeast genome (38.3%) and the box indicates the selected fragment (0–149 base pairs).</p
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