Central Asian Sources and Central Asian Research

In October 2014 about thirty scholars from Asia and Europe came together for a conference to discuss different kinds of sources for the research on Central Asia. From museum collections and ancient manuscripts to modern newspapers and pulp fiction and the wind horses flying against the blue sky of Mongolia there was a wide range of topics. Modern data processing and data management and the problems of handling five different languages and scripts for a dictionary project were leading us into the modern digital age. The dominating theme of the whole conference was the importance of collections of source material found in libraries and archives, their preservation and expansion for future generations of scholars. Some of the finest presentations were selected for this volume and are now published for a wider audience

Vergleichende Untersuchungen an der Netzhaut von Atheriniformes (Teleostei)

Die vorliegende Arbeit stellt eine vergleichende –anatomische und physiologische- Untersuchung an der Netzhaut von Atheriniformes (Hornhechte, fliegende Fische, Halbschnäbler, Ährenfische, Zwischenkärpflinge, u. a.) dar. Ziel dieser Studie ist es, unter Berücksichtigung der verwandtschaftlichen Verhältnisse zu klären, inwieweit sich in Morphologie und spektraler Empfindlichkeit der äußeren Retina Anpassungen an die visuelle Umwelt zeigen. 13 Arten aus 8 Familien wurden licht- und elektronenmikroskopisch untersucht: Dermogenys pusillus, Hyporamphus affinis (Hemiramphidae); Parexocoetus mento (Exocoetidae); Belone belone, Tylosurus crocodylus, Xenentodon cancila (Belonidae); Scomberesox saurus (Scomberesocidae); Oryzias celebenensis (Oryziatidae); Ameca splendens (Goodeidae); Melanotaenia maccullochi, Glossolepis incisus (Melanotaeniidae); Atherina boyeri, Telmatherina ladigesi (Atherinidae). Die spektrale Empfindlichkeit der Photorezeptoren wurde bei D. pusillus, B. belone, M. maccullochi, A. boyeri und T. ladigesi mikrospektrophotometrisch, bei M. maccullochi außerdem histochemisch (NBT-Färbung) untersucht. Der Retinaaufbau entspricht bei allen untersuchten Vertretern der für diurnale Teleostier typischen Duplexretina. Bezüglich der morphologischen Befunde und spektralen Ergebnisse lassen sich zwischen den einzelnen Familien und mitunter sogar Arten z. T. deutliche Unterschiede feststellen. Dabei treten innerhalb eines Auges häufig regionale Unterschiede auf. Allerdings weisen bestimmte Gruppen auch gemeinsame Merkmale auf. So stellen neben den bei allen untersuchten Vertretern vorkommenden gleichen und ungleichen Doppelzapfen, bei den Belonidae und Scomberesocidae lediglich lange Einzelzapfen ein regelmäßiges Musterelement dar. Die übrigen Vertreter besitzen dagegen, zumindest in bestimmten Regionen, zusätzlich kurze Einzelzapfen. Melanotaenia weist mittlere Einzelzapfen an Stelle der kurzen und langen Einzelzapfen auf. Bei den meisten Arten lassen sich sporadisch bis lokal häufig, vermehrt in der ventralen Region, sowohl lineare als auch trianguläre Dreifachzapfen beobachten, bei A. splendens sogar Vierfachzapfen. Charakteristisch für die Atherinifomes ist ein vitreo-skleraler Dichtegradient der Ellipsoid-Mitochondrien, aus dem bei einigen Vertretern Riesenmitochondrien am skleralen Ellipsoidende resultieren. Melanotaenia und Oryzias besitzen an der Ellipsoidspitze ellipsosomenähnliche Körper, Ameca dagegen echte Ellipsosomen, die möglicherweise eine Synapomorphie der Cyprinodontoidea darstellen und durch selektive Filterung vermutlich der Kontrastverstärkung dienen. Während die Stäbchenanordnung bei den Ährenfischartigen keinerlei Regelmäßigkeiten aufweist, bilden die Zapfen im helladaptierten Zustand hochgeordnete Muster aus, die mitunter bis in die Synapsenregion verfolgt werden können. Reine und verdrehte Reihenmuster, sowie Viereckmuster kommen bei nahezu allen Vertretern vor, pentagonale Muster dagegen nur sporadisch. Einen bis dato in dieser Form einmaligen Mustertyp stellt das hexagonale Muster in der dorsalen Retina von B. belone dar, der möglicherweise eine Anpassung an das Sehen bei niedrigeren Lichtintensitäten darstellt. Reine und verdrehte Reihenmuster sowie Viereckmuster stehen häufig in direktem Zusammenhang mit lokalen Doppelzapfendichtemaxima. Solche Dichtehöchstwerte finden sich in der Regel in Retinaregionen, die Sehreize aus den Hauptblickrichtungen verarbeiten. Diese sind bei den Atheriniformes zumeist nach anterior, anterior-dorsad, anterio-ventrad, sowie dorso-temporad gerichtet. Die funktionelle Bedeutung von Dichtemaxima, Zapfenmuster und Zapfenverhältnissen wird unter Berücksichtigung der Lebensgewohnheiten des jeweiligen Vertreters in Zusammenhang mit den photischen Bedingungen seines Lebensraumes diskutiert. Während das λmax der Stäbchen mit Wellenlängen um 506nm relativ konstant erscheint, erstreckt sich die spektrale Empfindlichkeit der Zapfen bei den Atheriniformes von 369nm (UV) bis 576nm (rot). Dabei weisen A. boyeri (blau/grün) ein dichromatisches und T. ladigesi (UV/blau/grün), D. pusillus (UV/grün/rot) sowie B. belone (blau/brün/rot) ein trichromatisches Sehen auf. Das Zapfenpigmentrepertoire von M. maccullochi bietet die Voraussetzung für tetrachromatisches Sehen (UV/violett, blau, grün, rot). Verschiedene Opsinfamilien bei Melanotaenia und Dermogenys zeigen Polymorphismus. Hinweise auf ein Rhodopsin/Porphyropsingemisch, dessen Verhältnis innerhalb der Retina variiert, finden sich bei Telmatherina. Die zahlreichen unterschiedlichen spektralen Empfindlichkeiten lassen sich als Anpassung an die spektralen Eigenschaften des Lebensraumes, die intraspezifische Kommunikation oder den Nahrungserwerb deuten. Dabei spielen der violette und ultraviolette Bereich des Spektrums unter Umständen eine besondere Rolle als „geheime Wellenlängen“ im Rahmen der innerartlichen Verständigung. Vermutlich dient UV-Empfindlichkeit auch der Kontrastverstärkung und erleichtert somit die Beutedetektion. Als gemeinsames Merkmal, das den Atherinoidei und Cyprinodontoidei fehlt, besitzen die Exocoetoidei pigmentierte Strukturen im Augenbinnenraum, die wahrscheinlich modifizierte Processus falciformis darstellen. Während die fliegenden Fische und Halbschnäbler lediglich pigmentierte Zapfen in der Augenkammer aufweisen, zeigen Scomberesox und vor allem die Belonidae ein horizontales intraokulares Septum, das möglicherweise der Streulichtabsorption und als Blendschutz dient. Die Ergebnisse insgesamt machen deutlich, dass bei den Atheriniformes neben hochkonservierten Merkmalen auch abgeleitete Retinamerkmale zu beobachten sind, deren Ausprägungen einem starken evolutiven Wandel unterliegen. Sie stellen die Voraussetzung für die zahlreichen, vom Grundplan der Ordnung abweichenden Anpassungen an die im jeweiligen Mikrohabitat vorherrschenden Lichtbedingungen sowie an verhaltensökologische Gegebenheiten dar

Requirements on Paramagnetic Relaxation Enhancement Data for Membrane Protein Structure Determination by NMR

SummaryNuclear magnetic resonance (NMR) structure calculations of the α-helical integral membrane proteins DsbB, GlpG, and halorhodopsin show that distance restraints from paramagnetic relaxation enhancement (PRE) can provide sufficient structural information to determine their structure with an accuracy of about 1.5 Å in the absence of other long-range conformational restraints. Our systematic study with simulated NMR data shows that about one spin label per transmembrane helix is necessary for obtaining enough PRE distance restraints to exclude wrong topologies, such as pseudo mirror images, if only limited other NMR restraints are available. Consequently, an experimentally realistic amount of PRE data enables α-helical membrane protein structure determinations that would not be feasible with the very limited amount of conventional NOESY data normally available for these systems. These findings are in line with our recent first de novo NMR structure determination of a heptahelical integral membrane protein, proteorhodopsin, that relied extensively on PRE data

Mapping Functional Interaction Sites of Human Prune C-Terminal Domain by NMR Spectroscopy in Human Cell Lysates

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The molecular pharmacology and in vivo activity of 2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)octanoic acid (YS121), a dual inhibitor of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase.

The microsomal prostaglandin E2 synthase (mPGES)-1 is one of the terminal isoenzymes of prostaglandin (PG) E2 biosynthesis. Pharmacological inhibitors of mPGES-1 are proposed as an alternative to nonsteroidal anti-inflammatory drugs. We recently presented the design and synthesis of a series of pirinixic acid derivatives that dually inhibit mPGES-1 and 5-lipoxygenase. Here, we investigated the mechanism of mPGES-1 inhibition, the selectivity profile, and the in vivo activity of α-(n-hexyl)- substituted pirinixic acid [YS121; 2-(4-chloro-6-(2,3-dimethylphenylamino) pyrimidin-2-ylthio)octanoic acid)] as a lead compound. In cell-free assays, YS121 inhibited human mPGES-1 in a reversible and noncompetitive manner (IC 50 = 3.4 μM), and surface plasmon resonance spectroscopy studies using purified in vitro-translated human mPGES-1 indicate direct, reversible, and specific binding to mPGES-1 (KD = 10-14 μM). In lipopolysaccharide-stimulated human whole blood, PGE2 formation was concentration dependently inhibited (IC50 =2 μM), whereas concomitant generation of the cyclooxygenase (COX)-2-derived thromboxane B2 and 6-keto PGF1α and the COX-1-derived 12(S)-hydroxy-5-cis-8,10- transheptadecatrienoic acid was not significantly reduced. In carrageenan-induced rat pleurisy, YS121 (1.5 mg/kg i.p.) blocked exudate formation and leukocyte infiltration accompanied by reduced pleural levels of PGE2 and leukotriene B4 but also of 6-keto PGF 1α. Taken together, these results indicate that YS121 is a promising inhibitor of mPGES-1 with anti-inflammatory efficiency in human whole blood as well as in vivo

Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics

The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphoblastic leukemia. Differences in protein interactions and activated signaling pathways that may be associated with the different diseases driven by p210 and p190 are unknown. We have performed a quantitative comparative proteomics study of p210 and p190. Strong differences in the interactome and tyrosine phosphoproteome were found and validated. Whereas the AP2 adaptor complex that regulates clathrin-mediated endocytosis interacts preferentially with p190, the phosphatase Sts1 is enriched with p210. Stronger activation of the Stat5 transcription factor and the Erk1/2 kinases is observed with p210, whereas Lyn kinase is activated by p190. Our findings provide a more coherent understanding of Bcr-Abl signaling, mechanisms of leukemic transformation, resulting disease pathobiology and responses to kinase inhibitors.Leukemia accepted article preview online, 23 January 2017. doi:10.1038/leu.2017.36

Heart failure and treatment with Sodium-glucose Co-transporter Inhibitor (SGLT2): dapagliflozin and its effects on the cardiac system

This article thoroughly examines the effectiveness of treatment with dapagliflozin, a sodium-glucose co-transporter inhibitor, in the context of heart failure. The primary focus of this analysis lies in evaluating patients' clinical condition, the diagnostic procedures employed, and the various medications used as part of the treatment regimen. The objective of this investigation is based on a meticulous analysis of relevant scientific articles. Classified as documentary research within the field of Applied Linguistics, this study draws upon research covering classification, pathophysiology, clinical presentation, diagnosis, pharmacological treatment, and the role of SGLT2 inhibitors in heart failure as its primary theoretical framework. The findings indicate dapagliflozin's efficacy in reducing the heart's ejection fraction, regardless of the presence of diabetes. However, it emphasizes the importance of a comprehensive medical assessment before initiating the use of this medication, highlighting the need for caution and appropriate professional supervision

A natural and readily available crowding agent: NMR studies of proteins in hen egg white

In vitro studies of biological macromolecules are usually performed in dilute, buffered solutions containing one or just a few different biological macromolecules. Under these conditions, the interactions among molecules are diffusion limited. On the contrary, in living systems, macromolecules of a given type are surrounded by many others, at very high total concentrations. In the last few years, there has been an increasing effort to study biological macromolecules directly in natural crowded environments, as in intact bacterial cells or by mimicking natural crowding by adding proteins, polysaccharides, or even synthetic polymers. Here, we propose the use of hen egg white (HEW) as a simple natural medium, with all features of the media of crowded cells, that could be used by any researcher without difficulty and inexpensively. We present a study of the stability and dynamics behavior of model proteins in HEW, chosen as a prototypical, readily accessible natural medium that can mimic cytosol. We show that two typical globular proteins, dissolved in HEW, give NMR spectra very similar to those obtained in dilute buffers, although dynamic parameters are clearly affected by the crowded medium. The thermal stability of one of these proteins, measured in a range comprising both heat and cold denaturation, is also similar to that in buffer. Our data open new possibilities to the study of proteins in natural crowded media. Proteins 2011. © 2010 Wiley-Liss, Inc

Atuação da ciclosporina no pós operatório de transplantes de coração no nordeste, noroeste e região metropolitana do espírito santo: Performance of cyclosporin in the post operation of heart transplantation in the northeast, northwest and metropolitan region of espírito santo

Este artigo tematiza a atuação da ciclosporina no pós-operatório de transplantes de coração no nordeste, noroeste e região metropolitana do Espírito Santo. O objeto de investigação é baseado em artigos. Este estudo se caracteriza como uma pesquisa documental, situada na Linguística Aplicada. Estudos sobre efeitos colaterais, contraindicações, indicações para transplante e recuperação após a transplantação são os principais referenciais teóricos utilizados para problematizar implicações no pós-operatório da ciclosporina. Os resultados mostram a necessidade do aprimoramento do uso adequado do medicamento para promover uma melhor atuação no pós-operatório de pacientes com rejeição do enxerto pós transplantes alogênicos, com ênfase no transplante cardíaco

Multiethnic Societies of Central Asia and Siberia Represented in Indigenous Oral and Written Literature

Central Asia and Siberia are characterized by multiethnic societies formed by a patchwork of often small ethnic groups. At the same time large parts of them have been dominated by state languages, especially Russian and Chinese. On a local level the languages of the autochthonous people often play a role parallel to the central national language. The contributions of this conference proceeding follow up on topics such as: What was or is collected and how can it be used under changed conditions in the research landscape, how does it help local ethnic communities to understand and preserve their own culture and language? Do the spatially dispersed but often networked collections support research on the ground? What contribution do these collections make to the local languages and cultures against the backdrop of dwindling attention to endangered groups? These and other questions are discussed against the background of the important role libraries and private collections play for multiethnic societies in often remote regions that are difficult to reach