Heparin-binding motif mutations of human diamine oxidase allow the development of a first-in-class histamine-degrading biopharmaceutical

<strong>Background:</strong> Excessive plasma histamine concentrations cause symptoms in mast cell activation syndrome, mastocytosis or anaphylaxis. Anti-histamines are often insufficiently efficacious. Human diamine oxidase (hDAO) can rapidly degrade histamine and therefore represents a promising new treatment strategy for conditions with pathological histamine concentrations. <strong>Results:</strong> Recombinant hDAO is rapidly cleared from the circulation in rats and mice. After replacement of positively charged amino acids of the heparin-binding motif with polar serine or threonine residues binding to heparin and heparan sulfate was strongly reduced. The double mutant rhDAO-R568S/R571T showed minimal cellular uptake. The short α-distribution half-life of the wildtype protein was eliminated and the clearance was significantly reduced in rodents. <strong>Conclusions: </strong>The successful decrease in plasma clearance of rhDAO by mutations of the heparin-binding motif with unchanged histamine-degrading activity represents the first step towards the development of rhDAO as a first-in-class biopharmaceutical to effectively treat diseases characterized by excessive histamine concentrations in plasma and tissues. <strong>Funding: </strong>Austrian Science Fund (FWF) Hertha Firnberg program grant T1135 (EG); ADD funding Sigrid Juselius Foundation, Medicinska Understödsförening Liv och Hälsa rft (TAS and SeV).

Using electron backscatter diffraction to determine the formation mechanism of mineral inclusions in garnet

&lt;p&gt;Determining the origin of mineral inclusions is a key problem in petrology. Assuming different inclusion formation mechanisms can lead to dramatically different petrological interpretations. Crystallographic orientation relationships (CORs), systematic relationships between the crystallographic orientations of crystals sharing boundary segments, are sensitive to the mechanisms of inclusion formation. Electron backscatter diffraction (EBSD) in the scanning electron microscope yields highly spatially resolved information about host-inclusion CORs. EBSD point analyses allow collection of large COR datasets, while retaining a link to the location of every measured inclusion and any shape preferred orientation (SPO) relative to host crystallography and microstructures. Based on combined COR, SPO and location information, we can differentiate between multiple origin hypotheses where COR formation is predicted, and the large number of measurements achievable allows observation of the relative frequency of different CORs.&lt;/p&gt;&lt;p&gt;Acicular rutile inclusions in garnet with SPOs parallel to garnet crystal directions are often interpreted based on microstructures alone as products of exsolution, implying the existence of precursor Ti-bearing garnet. We studied rutile needles from metapegmatite garnets from two localities with separate geological histories. Rutile needles occur in zones that extend parallel to garnet {112} (both localities) and {110} (one locality) crystal planes. Needles are elongated parallel to &lt;111&gt; (both localities) and &lt;100&gt; (one locality) directions in the garnet hosts. The majority of needles show a &amp;#8220;specific&amp;#8221; (completely fixed) COR to the garnet host. Several different CORs can be found within a single garnet domain and the frequency of different CORs varies both between domains from the same locality and between localities. Despite the existence of several CORs, there is a systematic link between the rutile-garnet COR exhibited by a given needle inclusion and its elongation direction relative to the crystallography of both garnet and rutile.&lt;/p&gt;&lt;p&gt;A comparison with literature datasets of CORs from garnets with acicular rutile inclusions reveals that both the type and frequencies of rutile-garnet CORs found in metapegmatite garnets differ strongly from those found in garnets of purely metamorphic origin. CORs judged to result in a poor alignment between rutile and garnet structures are considerably more frequent in the metapegmatite samples.&lt;/p&gt;&lt;p&gt;In garnets from one locality, the SPO of rutile needles does not favour all crystallographically equivalent garnet &lt;111&gt; directions equally. Instead, needles are preferentially elongated parallel to garnet &lt;111&gt; directions at high angles to the garnet facets defined by inclusion zoning. SPO and COR of the rutile needles thus depend on the orientation of the growing garnet interface, which is incompatible with an exsolution origin for these inclusions. Oriented nucleation of rutile at the garnet interface and subsequent simultaneous growth of both phases can account for these observations.&lt;/p&gt;&lt;p&gt;These results show the power of combining spatially resolved COR data with SPO information. An exsolution origin for rutile needles cannot be proposed based on needle SPO alone, and specific CORs are not necessarily indicative of an exsolution origin for rutile needles even if they occur together with an SPO relative to the garnet host.&lt;/p&gt;&lt;p&gt;We acknowledge funding by the Austrian Science Fund (FWF): I4285-N37.&lt;/p&gt;

Thallium mobility in mining wastes at the Crven Dol locality, Allchar deposit, North Macedonia

&lt;p&gt;In order to better understand the environmental behaviour of thallium, we have chosen the abandoned As&amp;#8211;Sb&amp;#8211;Tl&amp;#8211;Au Allchar deposit (North Macedonia) with unique mineral composition and high thallium grades of the ore. We used pore water analyses, selective extractions, single-crystal and powder X-ray diffraction (PXRD), SEM-EDS, electron microprobe analysis (EMPA), and Raman spectroscopy to determine the distribution and speciation of thallium in waste dump material at the Tl-rich Crven Dol locality in the northern part of the Allchar deposit.&lt;/p&gt;&lt;p&gt;PXRD studies showed that the various solid waste samples are comprised mostly of carbonates (dolomite and calcite), gypsum, quartz, muscovite, kaolinite-group minerals followed by orpiment, realgar, pyrite, marcasite, lorandite, and various iron and calcium arsenates and iron (hydro)oxides, both amorphous and crystalline. Raman spectra, SEM-EDS and EMPA also showed the presence of Ca-Fe-, Ca-Mn-, and Ca-Mg-arsenates.&lt;/p&gt;&lt;p&gt;The main primary source of Tl in the waste is lorandite (TlAsS&lt;sub&gt;2&lt;/sub&gt;), which occurs as prismatic crystals and anhedral grains up to 1 mm and is frequently intergrown with realgar. Other Tl sources, included in either realgar or orpiment, are minor Tl sulphosalts such as fangite (Tl&lt;sub&gt;3&lt;/sub&gt;AsS&lt;sub&gt;4&lt;/sub&gt;), raguinite (TlFeS&lt;sub&gt;2&lt;/sub&gt;), picotpaulite (TlFe&lt;sub&gt;2&lt;/sub&gt;S&lt;sub&gt;3&lt;/sub&gt;) and jankovi&amp;#263;ite (Tl&lt;sub&gt;5&lt;/sub&gt;Sb&lt;sub&gt;9&lt;/sub&gt;(As,Sb)&lt;sub&gt;4&lt;/sub&gt;S&lt;sub&gt;22&lt;/sub&gt;). The Tl dissolved during weathering is precipitated as micaceous subparallel crystals of poorly crystalline to amorphous thallium arsenates (representing previously unknown mineral species), forming porous aggregates up to 100 &amp;#181;m. These Tl arsenates are intergrown with dolomite and Ca-Fe-arsenates and appear as two chemically different phases. The first, more common phase shows a variable Tl:As ratio ranging from ca. 2.1 to 4.1 and a variable Ca content (2.2 to 4.1 at.%). In the second, Tl-richer phase, the Tl:As ratio varies from ca. 5.1 to 8.4. Raman spectra of the Tl arsenates display broad bands and may be divided in the fingerprint region into two relevant ranges, 350&amp;#8211;600 and 700&amp;#8211;900 cm&lt;sup&gt;&amp;#8722;1&lt;/sup&gt;, both attributed to arsenate tetrahedral complexes showing As&amp;#8211;O(&lt;em&gt;X&lt;/em&gt;) symmetric stretching with &lt;em&gt;X&lt;/em&gt; = H&lt;sup&gt;+&lt;/sup&gt; or H&lt;sub&gt;2&lt;/sub&gt;O.&lt;/p&gt;&lt;p&gt;Another relatively common Tl precipitate is dorallcharite [TlFe&lt;sup&gt;3+&lt;/sup&gt;&lt;sub&gt;3&lt;/sub&gt;(SO&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;(OH)&lt;sub&gt;6&lt;/sub&gt;], crystallizing in the form of tiny, well-formed platelets that are grouped into aggregates up to 400 &amp;#181;m in size. Tl is also accumulated in (probably cryptomelane-type) Mn oxides (up to 3.6 at.%), pharmacosiderite (up to 0.9 at.%), and jarosite (up to 0.9 at.%).&lt;/p&gt;&lt;p&gt;The pore water contained high aqueous concentrations of Tl (up to 660 &amp;#956;g&amp;#183;L&lt;sup&gt;&amp;#8722;1&lt;/sup&gt;) and As (up to 196 mg&amp;#183;L&lt;sup&gt;&amp;#8722;1&lt;/sup&gt;). Although these concentrations are low with respect to their total concentrations in the solid phase (Tl: 0.07-1.44 wt. %; As: 0.72-8.67 wt. %), mild extractions (ammonium nitrate and phosphate) mobilized up to 44% of the total Tl and 23% of the total As, indicating that a large amount of these toxic elements is bound weakly (sorption) to solids and can be easily mobilized into the pore water.&lt;/p&gt;&lt;p&gt;Financial support of the Austrian Science Fund (FWF) [P 30900-N28] is gratefully acknowledged.&lt;/p&gt;

Narratives in Motion: the Art of Dancing Stories in Antiquity and Beyond

The purpose of the symposium “Narratives in Motion. The Art of Dancing Stories in Antiquity and Beyond” was to make original contributions to the thriving field of study on ancient Greek and Roman dance by tackling this issue from an angle which is both specific in that it narrows down the focus on dance narrativity across different performance genres, and inclusive in that it encompasses transcultural, transhistorical and practice-based approaches. With eleven talks by classical and dance scholars and two performances by dance artists, the symposium was able to shed light on a range of practices, genres and cultural aspects relating to narrative dance in the ancient and, to a lesser degree, modern world. The event took place on 22-23 June 2018 at the Department of Classics of the University of Vienna, and was sponsored by the FWF-Austrian Science Fund (Project V442-G25 “Aischylos’ diegetisches Drama”).

The FWF’s Open Access Policy over the last 15 Years – Developments and Outlook

The report outlines the developments of the open access (OA) policy of the Austrian Science Fund (FWF) since its first release in 2004. Over the last 15 years, the FWF has not only continuously updated its OA policy but has also adapted its support mechanisms to include dedicated funding programmes and financial support structures for alternative publication venues and infrastructures. A brief analysis of the FWF’s open access funding will be provided in the second part of the article, which will conclude with an outlook of the upcoming revisions to the OA policy.

Life Writing Research Past and Present: Interview with Sidonie Smith and Julia Watson

On 16 November, 2017, the Austrian “Netzwerk Biographieforschung”,1 a network of life writing scholars and practitioners from various disciplines (history, literary studies, pedagogics, archival work, art, musicology) hosted its twelfth workshop at the University of Music and Performing Arts, Vienna. The organisers (Sarah Herbe, Julia Lajta-Novak and Melanie Unseld) were delighted to welcome two very special guests: Prof. Sidonie Smith and Prof. Julia Watson, whose vital contribution to autobiography theory need hardly be explained in the context of this journal. They had been invited on the occasion of the recent publication of Life Writing in the Long Run: A Smith and Watson Autobiography Studies Reader (Maize Books, 2016, available free online), which features a cross-section of their scholarship in the field over three decades. The following is an excerpt from the interview Sarah Herbe and Julia Lajta-Novak conducted with Sidonie Smith and Julia Watson, which addressed the differences between autobiographical and biographical modes, recent theoretical interventions in the field of life-writing studies, and topical issues such as the impact of “post-truth” on auto/biography scholars and the implications of the #MeToo movement as a massive autobiographical project. This work was supported by the Austrian Science Fund (FWF) under Grant V543-G23.