Mirrors of Heresy and Visions of Holiness: Using the Works of Marguerite Porete and Angela of Foligno to Examine Heresy and Holiness in Medieval Mysticism

The Reflective Essay focuses on aspects of the author’s research process, such as the importance of primary and secondary sources, in writing her paper, “Mirrors of Heresy and Visions of Holiness: Using the Works of Marguerite Porete and Angela of Foligno to Examine Heresy and Holiness in Medieval Mysticism.” Both Marguerite Porete and Angela of Foligno produced theological texts depicting the cultivation of a deep personal relationship with God and the attainment of spiritual perfection—a state of enlightenment characterized by the union of God and the soul through love. The two mystics would seem to occupy similar roles in the context of Medieval European religiosity; yet, while Marguerite was burned at the stake for heresy in 1310, Angela died a natural death in 1309, surrounded by a community of Franciscan followers, and she is now a canonized saint. The dramatically different circumstances surrounding Marguerite’s and Angela’s deaths elicit questions about the ways in which their lives diverged. Comparing and contrasting the lives and ideologies of these two female mystics through an analysis of their theological texts, this paper explores the Catholic Orthodoxy’s reactions to late thirteenth century female mystics who pushed the boundaries of conventional Orthodox structures and seeks to understand what distinguished Marguerite’s “heresy” from Angela’s “holiness.

Embodying the Empire: Singing Slave Girls in Medieval Islamicate Historiography

This thesis explores the ways in which the qiyan—highly trained female singers held as slaves by the courtly elite in ‘Abbasid Baghdad and Umayyad Andalusia—were represented and depicted in Medieval literary and historical narratives. More specifically, I am interested in examining how Medieval authors used depictions of the qiyan as rhetorical strategies for advancing the broader political and philosophical agendas that their texts were intended to address. Because the qiyan did not write their own biographies, our understanding of these singing slave women cannot be separated from the broader literary, political, philosophical, and theological agendas of the texts in which they are discussed. In light of this reality, my thesis does not attempt to reconstruct the experiences of the qiyan themselves. Rather, the following analysis seeks to return the qiyan to their original context by considering how the subject of the qiyan was mobilized for specific narrative purposes by Medieval authors

Darstellung neuer Ansamycin-Derivate über Mutasynthese in Kombination mit Semisynthese

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Multiplexed heat shock protein microarray as a screening platform for the selection of novel drug compounds

In diseases such as cancer, Alzheimer’s disease or malaria, disease-related proteins take advantage of the heat shock protein (HSP) control system for their own activation or maturation. There is a quest to find inhibitors that specifically bind to the HSPs. Here, we report on a novel multiplexed assay system for inhibitor screening based on a protein microarray (MA) technique that was developed for routine applications with storable MAs. Purified HSPs are printed as full-length proteins on microarrays and used as a drug target for the screening of new inhibitors. Derivatives obtained by a combination of biological and chemical synthesis were tested as competitors of ATP with a suggested affinity for several HSP proteins which are hHSP from human, AtHSP83 (Arabidopsis thaliana) and HtpG from Helicobacter pylori. Some of these new derivatives exerted selectivity between human and bacterial heat shock proteins. Printed human HSP90 was used to test the binding of denatured proteins on the client binding site of human HSP90, since the full-length HSP maintains the capability to bind putative clients or cochaperones. Initial data revealed that the microarray application can be used to identify directly elevated heat-shock protein levels in cancer cell lysates. We suggest that microarray-based assaying of HSP levels can be used as a marker for determining stress levels.DFG/Ki 13-

Quick, accurate, smart: 3D computer vision technology helps assessing confined animals' behaviour

Mankind directly controls the environment and lifestyles of several domestic species for purposes ranging from production and research to conservation and companionship. These environments and lifestyles may not offer these animals the best quality of life. Behaviour is a direct reflection of how the animal is coping with its environment. Behavioural indicators are thus among the preferred parameters to assess welfare. However, behavioural recording (usually from video) can be very time consuming and the accuracy and reliability of the output rely on the experience and background of the observers. The outburst of new video technology and computer image processing gives the basis for promising solutions. In this pilot study, we present a new prototype software able to automatically infer the behaviour of dogs housed in kennels from 3D visual data and through structured machine learning frameworks. Depth information acquired through 3D features, body part detection and training are the key elements that allow the machine to recognise postures, trajectories inside the kennel and patterns of movement that can be later labelled at convenience. The main innovation of the software is its ability to automatically cluster frequently observed temporal patterns of movement without any pre-set ethogram. Conversely, when common patterns are defined through training, a deviation from normal behaviour in time or between individuals could be assessed. The software accuracy in correctly detecting the dogs' behaviour was checked through a validation process. An automatic behaviour recognition system, independent from human subjectivity, could add scientific knowledge on animals' quality of life in confinement as well as saving time and resources. This 3D framework was designed to be invariant to the dog's shape and size and could be extended to farm, laboratory and zoo quadrupeds in artificial housing. The computer vision technique applied to this software is innovative in non-human animal behaviour science. Further improvements and validation are needed, and future applications and limitations are discussed.</p

The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma

The complex architecture of transmembrane proteins requires quality control (QC) of folding, membrane positioning, and trafficking as prerequisites for cellular homeostasis and intercellular communication. However, it has remained unclear whether transmembrane protein-specific QC hubs exist. Here we identify cereblon (CRBN), the target of immunomodulatory drugs (IMiDs), as a co-chaperone that specifically determines chaperone activity of HSP90 toward transmembrane proteins by means of counteracting AHA1. This function is abrogated by IMiDs, which disrupt the interaction of CRBN with HSP90. Among the multiple transmembrane protein clients of CRBN-AHA1-HSP90 revealed by cell surface proteomics, we identify the amino acid transporter LAT1/CD98hc as a determinant of IMiD activity in multiple myeloma (MM) and present an Anticalin-based CD98hc radiopharmaceutical for MM radio-theranostics. These data establish the CRBN-AHA1-HSP90 axis in the biogenesis of transmembrane proteins, link IMiD activity to tumor metabolism, and nominate CD98hc and LAT1 as attractive diagnostic and therapeutic targets in MM

Marathons and myasthenia gravis: a case report.

The cardinal symptoms of auto-immune myasthenia gravis are fatigue and weakness. Endurance events such as marathon running would seem incompatible with this chronic disease. Many patients stop sport altogether. There is limited literature of patients with auto-immune myasthenia gravis undergoing regular endurance exercise. We report the case of a 36-year-old female who began long-distance running whilst experiencing initial symptoms of myasthenia gravis. She was diagnosed with auto-immune myasthenia gravis and whilst advised to stop all sport, her way of fighting and living with this chronic and unpredictable disease was to continue running to maintain a healthy body and mind. Despite suffering from ocular, bulbar and localized limb fatigability, she managed to complete multiple marathons and achieve disease stability with cholinesterase inhibitors. Marathon and half-marathon running lead to distinct changes in mediators of inflammation in an exercise-dose-dependent manner. Despite symptoms of weakness and fatigue in certain muscles in myasthenia gravis, physical exertion remains possible and may not worsen symptoms as demonstrated in this case and recent studies. The immunomodulatory role of exercise could be considered in this case however this hypothesis remains to be confirmed in future studies with quantitative data

Mechanisms of amyloid formation revealed by solution NMR

Amyloid fibrils are proteinaceous elongated aggregates involved in more than fifty human diseases. Recent advances in electron microscopy and solid state NMR have allowed the characterization of fibril structures to different extents of refinement. However, structural details about the mechanism of fibril formation remain relatively poorly defined. This is mainly due to the complex, heterogeneous and transient nature of the species responsible for assembly; properties that make them difficult to detect and characterize in structural detail using biophysical techniques. The ability of solution NMR spectroscopy to investigate exchange between multiple protein states, to characterize transient and low-population species, and to study high molecular weight assemblies, render NMR an invaluable technique for studies of amyloid assembly. In this article we review state-of-the-art solution NMR methods for investigations of: (a) protein dynamics that lead to the formation of aggregation-prone species; (b) amyloidogenic intrinsically disordered proteins; and (c) protein–protein interactions on pathway to fibril formation. Together, these topics highlight the power and potential of NMR to provide atomic level information about the molecular mechanisms of one of the most fascinating problems in structural biology

Targeting heat-shock-protein 90 (Hsp90) by natural products: Geldanamycin, a show case in cancer therapy

Covering: 2005 to 2013 In this review recent progress in the development of heat shock proteins (Hsp90) in oncogenesis is illuminated. Particular emphasis is put on inhibitors such as geldanamycin and analogues that serve as a natural product show case. Hsp90 has emerged as an important target in cancer therapy and/or against pathogenic cells which elicit abnormal Hsp patterns. Competition for ATP by geldanamycin and related compounds abrogate the chaperone function of Hsp90. In this context, this account pursues three topics in detail: a) Hsp90 and its biochemistry, b) Hsp90 and its role in oncogenesis and c) strategies to create compound libraries of structurally complex inhibitors like geldanamycin on which SAR studies and the development of drugs that are currently in different stages of clinical testing rely. © The Royal Society of Chemistry 2013