bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of non‐Rehm–Weller kinetics in the electron transfer from trivalent phosphorus compounds to singlet excited sensitizers
Authors: Yasui Shinro , Tsujimoto Munekazu
Published: July 2013

Singlet excited states (1S* and 1S+*) of neutral and monocationic sensitizers, S and S+, respectively, were quenched by electron transfer (ET) from a variety of trivalent phosphorus compounds (Z3P). The quenching rate constants kq, which are equal to the rate constants kET of the ET from Z3P to 1S* or 1S+*, were determined by the Stern–Volmer method. The logarithm of kET was plotted against free‐energy change ΔG0 of the ET. The plot deviated upward from the line predicted by the Rehm–Weller (RW) theory in the endothermic region, the deviation being larger in the ET to a neutral acceptor 1S* than in the ET to a cationic acceptor 1S+*. Such a kinetic behavior is in sharp contrast to that observed in the ET from amines (R3N), where the ET to either neutral or cationic acceptor takes place according to the RW prediction. The ET from a donor, Z3P or R3N, to a neutral acceptor 1S* is a charge‐separation type, during which electrostatic attraction between the donor and the acceptor is generated, whereas the ET to a cationic acceptor 1S+* is a charge‐shift type, which results in neither electrostatic attraction nor repulsion. Difference in kinetics–energetics relationship by the type of ET, which is not recognized in the ET from R3N donor, becomes “visible” when Z3P is used as a donor. Copyright © 2013 John Wiley & Sons, Ltd.
Density functional theory and time‐dependent density functional theory study on a series of iridium complexes with tetraphenylimidodiphosphinate ligand
Authors: Song Ming‐Xing , Hao Zhao‐Min , Wu Zhi‐Jian , Song Shu‐Yan , Zhou Liang , Deng Rui‐Ping , Zhang Hong‐Jie
Published: July 2013

A series of heteroleptic cyclometalated Ir(III) complexes for organic light‐emitting diodes (OLEDs) application have been investigated theoretically to explore their electronic structures and spectroscopic properties. The geometries, the electronic structures, the lowest‐lying singlet absorptions and triplet emissions of Ir(dfppy)2(tpip), Ir(tfmppy)2(tpip), and theoretically designed models of Ir(ppy)2(tpip) were investigated with the density functional theory (DFT)‐based approaches, where ppy = 2‐phenylpyridine, dfppy = 4,6‐difluorophenylpyridine, tfmppy = 4‐trifluoromethylphenylpyridine, and tpip = tetraphenylimidodiphosphinate. Their structures in the ground and their excited states have been optimized at the DFT/Becke 3‐parameter Lee Yang Parr (B3LYP)/Los Alamos National Laboratory 2‐double‐z (LANL2DZ) and time‐dependent DFT/B3LYP/LANL2DZ levels, and the lowest absorptions and emissions were evaluated at B3LYP and M062X level of theory, respectively. Furthermore, the energy transfer mechanism together with the advantage of low efficiency roll‐off for these complexes also can be analyzed here. Copyright © 2013 John Wiley & Sons, Ltd.
The influence of hydrophilic properties on the venting of foamy three phase systems
Authors: Leimeister Henrik , Steinbach Jörg
Published: July 2013

The correct design of a safety valve or rupture disk can only be done if predictions on the venting behavior can be made. To date, those predictions have limitations with regard to foaming or highly viscous systems. An experimental study is presented that describes the influence of hydrophilic particles on the venting of strongly and weakly foaming systems. It is shown that hydrophilic particles increase the mass discharge over time and reduce the pressure decrease over time by increasing the foaming of aqueous systems. These effects are not significantly influenced by the reactor characteristics. At higher additive concentrations, the addition of particles is not as influential anymore. Thus, models for foamy two‐phase systems are applicable for the design of the described foamy three‐phase systems as well. © 2013 American Institute of Chemical Engineers Process Saf Prog 32: 239–243, 2013
Time‐resolved free carrier lifetime microscopy in bulk GaN
Authors: Šcˇajev Patrik , Nargelas Saulius , Jarašiūnas Kęstutis
Published: July 2013

A novel setup for lifetime microscopy measurements was designed and applied for carrier lifetime mapping in a bulk GaN. Photoexcitation by a picosecond UV pump and detection of time‐resolved free carrier absorption (FCA) images on a CCD camera enabled the mapping of carrier lifetime distribution with a spatial resolution of 5 μm. The spatial variation of lifetime in the bulk HVPE‐grown GaN revealed the presence of different‐size crystalline grains, with lifetime peaking up to 70 ns in the centers of the largest grains (∼20 μm in diameter) and dropping to 10 ns in the small ones, while the spatially averaged lifetime was 40 ns. The inhomogeneity was ascribed to the interplay of nonradiative diffusion‐limited recombination at grain boundaries and a bulk lifetime in the crystallite centers. The numerical solution of spatially‐resolved carrier decay rate in the crystallite centers at high injection levels and comparison with experimental data provided a bulk nonradiative recombination time of ∼70 ns. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Cu particle seeded InP–InAs axial nanowire heterostructures
Authors: Hillerich Karla , Ghidini Dario S. , Dick Kimberly A. , Deppert Knut , Johansson Jonas
Published: July 2013

magnified image

We demonstrate the epitaxial growth of alternating InP–InAs nanowire heterostructures using Cu seed particles in MOVPE. We observe extraordinary early stages in the formation of InAs segments, e.g. three‐dimensional nucleation instead of step‐flow growth. Furthermore, InAs segments of thin nanowires exhibit extended 4H crystal structure.

magnified image

Color coded XEDS elemental map of a typical InP–InAs nanowire heterostructure seeded by a Cu particle.

(© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
High‐gain observers and linear output regulation for hybrid exosystems
Authors: Cox Nicholas , Marconi Lorenzo , Teel Andrew
Published: July 2013

We consider the hybrid output regulation problem for minimum phase linear systems with relative degree greater than one. In the hybrid output regulation problem, an exosystem provides a disturbance or tracking signal that must be matched via an internal model in order to asymptotically regulate the error. This hybrid exosystem is a linear system that experiences periodic jumps. In this context, we build upon previous works in hybrid output regulation by showing how high‐gain observers can successfully overcome the obstacle of high relative degree. In certain scenarios, they can also be used to stabilize the hybrid internal model dynamics through jumps. Copyright © 2013 John Wiley & Sons, Ltd.
Stress‐reduction Interventions in an Australian University: A Case Study
Authors: Pignata Silvia , Winefield Anthony H.
Published: July 2013

We examined the effects of awareness of stress‐reduction interventions on employee well‐being and work attitudes using a mixed methods design. Cross‐sectional data are presented from 247 employees who completed questionnaires in 2004 at one Australian university. Analyses indicated that employees, who reported that interventions had been undertaken, scored higher on job satisfaction, affective organizational commitment, perceived procedural justice and trust in senior management than those who were not aware of the measures, although they did not differ in psychological strain. Details of the stress‐reduction interventions implemented by the Occupational Health and Safety department at the university are also reported. Thematic analyses of the perceived causes of both decreases and increases in stress for employees showed that staff reported workload and staffing pressures as key sources of increases in stress. On the other hand, new supervisors and/or management were identified as sources of decreased stress. Areas for consideration in future efforts to develop and refine stress interventions are also discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Review of wound ballistic research and its applicability to wildlife management
Authors: Caudell Joe N.
Published: July 2013

Wound ballistics is a science that has been gaining attention in wildlife management because of the movement toward non‐lead bullets for hunting and wildlife management projects. Wildlife biologists and managers are interested in evaluating new bullet technologies and using traditional bullets outside of their initial design parameters; however, much of the background and science that is involved in a wound ballistic study is outside of a typical wildlife biologist's training. I present a review of major wound ballistic history and background, including theories of how bullets wound and kill, and I review the primary techniques used for wound ballistic research. I found that most of the wound ballistic literature is found in a wide range of publications in both gray and primary literature; however, little work has been published that uses these techniques to investigate wound ballistics for wildlife management. Many of the techniques described for assessing the terminal ballistic for medical, military, and law enforcement purposes can be applied in the wildlife management field. © 2013 The Wildlife Society.
Dietary Intake and Food Sources of EPA, DPA and DHA in Australian Children
Authors: Rahmawaty Setyaningrum , Charlton Karen , Lyons‐Wall Philippa , Meyer Barbara J.
Published: July 2013

Secondary analysis of the 2007 Australian National Children's Nutrition and Physical Activity survey was undertaken to assess the intake and food sources of EPA, DPA and DHA (excluding supplements) in 4,487 children aged 2–16 years. An average of two 24‐h dietary recalls was analysed for each child and food sources of EPA, DPA and DHA were assessed using the Australian nutrient composition database called AUSNUT 2007. Median (inter quartile range, IQR) for EPA, DPA and DHA intakes (mg/day) for 2–3, 4–8, 9–13, 14–16 year were: EPA 5.3 (1.5–14), 6.7 (1.8–18), 8.7 (2.6–23), 9.8 (2.7–28) respectively; DPA 6.2 (2.2–14), 8.2 (3.3–18), 10.8 (4.3–24), 12.2 (5–29) respectively; and DHA 3.9 (0.6–24), 5.1 (0.9–26), 6.8 (1.1–27), 7.8 (1.5–33) respectively. Energy‐adjusted intakes of EPA, DPA and DHA in children who ate fish were 7.5, 2 and 16‐fold higher, respectively (P < 0.001) compared to those who did not eat fish during the 2 days of the survey. Intake of total long chain n‐3 PUFA was compared to the energy adjusted suggested dietary target (SDT) for Australian children and 20 % of children who ate fish during the 2 days of the survey met the SDT. Fish and seafood products were the largest contributors to DHA (76 %) and EPA (59 %) intake, while meat, poultry and game contributed to 56 % DPA. Meat consumption was 8.5 times greater than that for fish/seafood. Australian children do not consume the recommended amounts of long chain omega‐3 fatty acids, especially DHA, which could be explained by low fish consumption.
Aberrant Sphingolipid Metabolism in the Human Fallopian Tube with Ectopic Pregnancy
Authors: Gao Xiaolin , Ning Nannan , Kong Beihua , Xu Yongping , Xu Hui , Zhou Chengjun , Li Su , Shao Yi , Qiu Jianqing , Li Jingxin
Published: July 2013

Sphingosine 1‐phosphate (S1P), a product of sphingomyelin metabolism, is generated via phosphorylation of sphingosine by sphingosine kinases (SphK). It acts via a family of G protein‐coupled receptors or as an intracellular second messenger for agonists acting through the S1P receptors (S1P1–5). In our study, the expression of SphK1 and S1P1 was identified by immunohistochemistry and immunoblot. The concentration of S1P was measured using ELISA. The spontaneous contraction of isolated fallopian tube strips was determined by tension recording. Our results showed that SphK1 and S1P1 were localized in the fallopian tube epithelial cells. In addition, smooth muscle cells also contained S1P1. Compared with the intrauterine pregnancy group, SPHK1 and S1P1 were overexpressed in ectopic pregnancy. However, the S1P concentration within the human oviduct from ectopic pregnancy subjects was largely reduced than that from normal pregnancy subject. The results from tension recording indicated that exogenous and intracellularly generated S1P can regulate the spontaneous contraction of oviduct isolated from rats and human. In conclusion, the sphingolipid metabolism signal pathway functionally existed in the human fallopian tube. Aberrant sphingolipid metabolism in the human fallopian tube may be involved in ectopic pregnancy.
The roles of internal locus of control and neighborhood affluence in predicting the continuity of negative self‐feelings from adolescence to young adulthood
Authors: Pals Heili , Kaplan Howard B.
Published: July 2013

The present study examines the moderating effect of locus of control on the continuity in negative self‐feelings from adolescence to young adulthood. We use longitudinal data of 1296 respondents from adolescence (11–13 years old) to young adulthood (20–24 years old). Using interaction effects in linear regression with robust standard errors we find that those with an internal locus of control experience stronger continuity in negative self‐feelings from adolescence to young adulthood. Furthermore, based on both self‐reported and objective measures of neighborhood status, internal locus of control increases the continuity in negative self‐feelings in the transition to adulthood in disadvantaged neighborhoods but not in advantaged neighborhoods. Thus, locus of control acts as a maladaptive mechanism in less affluent neighborhoods. This result demonstrates the importance of considering both the individual social psychological and the contextual sociological perspectives when investigating the role of internal locus of control on the perpetuation of negative self‐feelings.
The essential gene YMR134W from Saccharomyces cerevisiae is important for appropriate mitochondrial iron utilization and the ergosterol biosynthetic pathway
Authors: Moretti-Almeida Gabriel , Netto Luis E.S. , Monteiro Gisele
Published: July 2013

A thermosensitive strain (YMR134Wts
) of the essential gene YMR134W presented up to 40% less ergosterol, threefold lower oxygen consumption and impaired growth on respiratory conditions. The iron content in the mitochondrial fraction of YMR134Wts
cells was considerably low, despite these cells uptake and accumulate more iron from the culture media than wild‐type cells. YMR134Wts
cells were also more susceptible to oxidative stress. The results suggest that Ymr134wp is essential to aerobic growth due to its function in ergosterol biosynthesis, playing a role in maintaining mitochondrial and plasma membrane integrity and consequently impacting the iron homeostasis, respiratory metabolism and antioxidant response.
A generic rate law for surface‐active enzymes
Authors: Kartal Önder , Ebenhöh Oliver
Published: July 2013

Many biochemical reactions are confined to interfaces, such as membranes or cell walls. Despite their importance, no canonical rate laws describing the kinetics of surface‐active enzymes exist. Combining the approach chosen by Michaelis and Menten 100 years ago with concepts from surface chemical physics, we here present an approach to derive generic rate laws of enzymatic processes at surfaces. We illustrate this by a simple reversible conversion on a surface to stress key differences to the classical case in solution. The available area function, a concept from surface physics which enters the rate law, covers different models of adsorption and presents a unifying perspective on saturation effects and competition between enzymes. A remarkable implication is the direct dependence of the rate of a given enzyme on all other enzymatic species able to bind at the surface. The generic approach highlights general principles of the kinetics of surface‐active enzymes and allows to build consistent mathematical models of more complex pathways involving reactions at interfaces.
Pitfalls bei Gerinnungsuntersuchungen
Authors: Gähler Anita , Wuillemin Walter A.
Published: July 2013

Gerinnungsuntersuchungen unterliegen vielfachen präanalytischen und analytischen Einflüssen. Verschiedene Antikoagulantien beeinflussen unterschiedliche Gerinnungsanalysen unterschiedlich stark. Der Quick wird beispielsweise durch Vitamin K-Antagonisten dosisabhängig erniedrigt, aber auch die neuen oralen Antikoagulantien verändern bestimmte Gerinnungszeiten, z. B. wird der Quick durch Rivaroxaban deutlich erniedrigt. Bei der Anti-Xa-Aktivitätsmessung ist zu beachten, dass nicht nur Heparine die Anti-X-Aktivität erhöhen, sondern auch orale Anti-Xa-Hemmer wie das Rivaroxaban und es dadurch zu Fehlinterpretationen kommen kann. Generell gilt für Gerinnungsuntersuchungen, dass diese nur im Zusammenhang mit der Klinik (unter anderem Blutungssituation, thromboembolische Ereignisse, Niereninsuffizienz, Medikamente und insbesondere Antikoagulantien und Aggregationshemmer) und mit dem Wissen um die verwendeten Testsysteme interpretiert werden können. Anhand von Fallbeispielen werden in diesem Artikel Fallstricke bei Gerinnungsuntersuchungen aufgezeigt.
Pitfalls bei Laborwerten – Elektrolyte, Harnstoff und Kreatinin
Authors: Risch Lorenz , Hess Bernhard
Published: July 2013

Bei der Einschätzung von Parametern des Elektrolythaushalts und der Nierenfunktion kommen Überlegungen zur Pathophysiologie und zu Referenzwerten zum Tragen. Eine Hyponatriämie ist meistens durch einen Wasserüberschuss bedingt, für welchen die Flüssigkeitsrestriktion die Maßnahme der Wahl darstellt. Eine verminderte Natriumkonzentration im Harn sollte klinisch eine Beurteilung des Volumenstatus nach sich ziehen, um differentialdiagnostisch die richtigen Schlüsse zu ziehen. Die fraktionierte Natriumexkretion, vor allem aber auch die fraktionierte Harnstoffexkretion, geben bei Verdacht auf ein akutes Nierenversagen Hinweise auf eine prärenale oder renale Ursache. Störungen des Kaliumhaushalts können im Rahmen von Veränderungen in der Zufuhr, in der renalen Elimination oder in der Verteilung zwischen extra- und intrazellulärem Kompartiment auftreten. Der transtubuläre Kaliumgradient hilft in der ätiologischen Klärung einer Hyperkaliämie. Zur Einschätzung der Nierenfunktion ist die Harnstoffkonzentration im Serum ungeeignet. Jegliche Einschätzung der Nierenfunktion soll mit der Bestimmung von Serumkreatinin beginnen und von einer Schätzung der glomerulären Filtration (eGFR) nach der CKD-EPI Formel begleitet werden. Allerdings ist anzumerken, dass diese Schätzungen die tatsächliche GFR vor allem im leicht erniedrigten und normalen Bereich unterschätzen kann. Paradoxerweise überschätzt die CKD-EPI bei älteren Personen, aber auch bei hospitalisierten Patienten die tatsächliche GFR, was sich in Medikationsfehlern auswirken kann. Grund für diese Abweichungen sind non-renale Einflussfaktoren auf die Kreatininkonzentration im Serum. Eine Clearancemessung kann diesbezüglich genauere Informationen liefern.
Abklärung erhöhter Leberwerte
Authors: Oberacher Marcos , Müllhaupt Beat
Published: July 2013

Die Bestimmung der Leberwerte im Serum gehört heute zu den häufigsten Laboruntersuchungen in der ärztlichen Praxis. Leberwerte werden nicht nur bei spezifischen Lebererkrankungen, sondern häufig bei der Abklärung eines unklaren Krankheitsbildes, sowie bei asymptomatischen Patienten im Rahmen eines „check-ups“ bestimmt. Oft ist ein Laborbefund nicht einfach zu beurteilen und es gibt keine kontrollierte klinische Studie, welche uns als Grundlage für Empfehlungen hinsichtlich eines rationalen Einsatzes von weiteren Abklärungen dient. Im ersten einführenden Abschnitt der vorliegenden Arbeit werden wir mögliche Algorithmen bei der Abklärung von erhöhten Leberwerten aufzeigen, in zweiten Abschnitt illustrieren vier Fallberichte aus der täglichen Praxis mögliche Ursachen von erhöhten Leberwerten.
Sinn und Unsinn toxikologischer Laboranalytik im klinischen Alltag
Authors: Bodmer Michael , Rentsch Katharina M.
Published: July 2013

Drogenscreeningtests mittels Immunoassay werden im klinischen Alltag immer wieder durchgeführt. Diese Tests detektieren je nach Hersteller die nachzuweisenden Substanzen sehr unterschiedlich. So können positive Messergebnisse auch durch Medikamente hervorgerufen werden, die nicht zur untersuchten Substanzklasse gehören. Andererseits kann es zu falsch negativen Resultaten kommen, wenn ein Patient eine Substanz eingenommen hat, die vom Antikörper im eingesetzten Test nicht erkannt wird. Deshalb müssen unplausible Resultate hinterfragt werden. Chromatographische Bestätigungs- und Screeningmethoden sind in der Durchführung und Interpretation aufwendiger und werden nur von wenigen Laboratorien angeboten. Ihre Spezifität ist aber sehr gut und eine Vielzahl verschiedener Substanzen können nachgewiesen werden, abhängig von der verwendeten Massenspektrenbibliothek. Liegt aufgrund der klinischen Beurteilung ein möglicher Vergiftungsfall vor, können Drogenscreeningtests von Nutzen sein, eine eingenommen Substanz- oder Substanzgruppe nachzuweisen, das klinische Bild kann jedoch durch Resultate dieser qualitativen Tests in der Regel nicht erklärt werden. Zudem konnte bis jetzt nicht gezeigt werden, dass durch diese Tests die Triage, Behandlung, Diagnostik oder die weitere Therapie vergifteter Patienten in klinisch relevanter Weise beeinflusst werden kann. Die quantitative Bestimmung von Einzelsubstanzen im Blut erlaubt zum Beispiel bei der Einnahme von Paracetamol oder Methanol eine Abschätzung der Prognose und hilft, die Indikation spezifischer Therapien zu stellen. Neue Designerdrogen können mit den klassischen Drogenscreeningtests nicht detektiert werden und müssen mittels chromatographischer Methoden identifiziert werden.
Zeitpunkt der Entfernung des Wundverbands bei primär heilenden chirurgischen Wunden: Eine Meta-Analyse
Authors: Eberhardt Doris , Berg Almuth , Fleischer Steffen , Langer Gero
Published: July 2013

Die Entstehung einer chirurgischen Wundinfektion soll unter anderem durch eine sachgerechte postoperative Versorgung der Wunde verhindert werden. Gerade die Dauer der Wundabdeckung wird derzeit jedoch unterschiedlich gehandhabt und empfohlen. Ziel der systematischen Übersichtsarbeit war es deshalb, die Bedeutung des Zeitpunkts der Entfernung des Wundverbands bei primär heilenden chirurgischen Wunden für die Entstehung einer Wundinfektion zu bewerten. Die Literaturrecherche erfolgte im August 2011 in den Datenbanken MEDLINE, EMBASE, CINAHL, Cochrane – CENTRAL sowie in weiteren Quellen durch Handsuche. Es wurden alle randomisierten kontrollierten Studien eingeschlossen, in denen die generelle Abdeckung und Nichtabdeckung der Wunde sowie unterschiedliche Zeitpunkte der Entfernung des Wundverbands miteinander verglichen wurden. Die Erstellung der systematischen Übersichtsarbeit und Meta-Analyse erfolgte nach den Empfehlungen der Cochrane Collaboration. Acht Studien mit insgesamt 2097 Teilnehmenden wurden in die Meta-Analyse eingeschlossen, wobei alle Studien ein unklares oder hohes Bias-Risiko aufwiesen. Die Meta-Analyse erbrachte keinen Hinweis darauf, dass durch eine frühzeitige Entfernung des Wundverbands im Gegensatz zur späten Entfernung die Entstehung von Wundinfektionen beziehungsweise -komplikationen bei primär heilenden chirurgischen Wunden begünstigt wird: Risikodifferenz (RD) – 0,01; 95 %-Konfidenzintervall (CI) – 0,03; 0,01. Aufgrund der methodischen Limitationen der Studien sind jedoch weitere aussagekräftige Primärstudien zur Sicherung der Ergebnisse notwendig.
Wenn's nicht nur juckt oder brennt: Klinik und Behandlung sexuell übertragbarer Erkrankungen (Teil 2)
Authors: Vuichard Danielle , Itin Peter
Published: July 2013

In diesem zweiten Teil vermitteln wir Ihnen eine Übersicht über die genitale Ulkuskrankheit. Typische Erreger sind das Herpes-simplex-Virus, Treponema pallidum und Chlamydia trachomatis. Wie auch bei der Urethritis und den Genitalwarzen bergen diese Erreger, wenn unbehandelt, das Risiko für Spätkomplikationen und erhöhen die Transmission und Akquisition von HIV. Luetische Spätfolgen beinhalten die Mesaortitis luetica mit drohendem Aortenaneurysma sowie Tabes dorsalis und progressive Paralyse. Der Schwerpunkt liegt in der Beschreibung der typischen klinischen Manifestationen der einzelnen Erreger, der teilweise komplexen Diagnostik sowie dem Management basierend auf den aktuellsten internationalen Richtlinien.
Radikale zytoreduktive Chirurgie mit hyperthermer intraperitonealer Chemotherapie (HIPEC) als kurativer Ansatz zur Behandlung primärer und sekundärer Peritonealtumore
Authors: Lehmann Kuno , Gertsch Philippe , Vonlanthen René
Published: July 2013

Bei Patienten mit einer Peritonealkarzinose bietet die radikale zytoreduktive Chirurgie (ZRC) mit anschliessender hyperthermer intraperitonealer Chemotherapie (HIPEC) bei gut selektionierten Patienten eine gute Prognose hinsichtlich des Langzeitüberlebens. Voraussetzung dafür ist eine radikale Tumorresektion mit dem Ziel, keine makroskopisch sichtbaren Tumorresiduen zu hinterlassen. Im direkten Anschluss erfolgt intraoperativ eine hypertherme intraabdominelle Chemotherapie zur Behandlung und Entfernung allfälliger mikroskopischer Tumorresiduen. Die perioperative Morbidität und Mortalität ist vergleichbar mit anderen grossen viszeralchirurgischen Eingriffen. Eine ZRC und HIPEC sollte als Teil eines multimodalen Therapiekonzeptes bei Patienten mit peritonealem Befall durch Appendixtumoren, kolorektalen Karzinomen oder beim primären peritonealen Mesotheliom evaluiert werden. Zurückhaltender ist man aktuell mit der Indikationsstellung beim Ovarial- und Magenkarzinom.
Die Zukunft der Neonatologie: Möglichkeiten und Grenzen
Authors: Bucher Hans Ulrich
Published: July 2013

Die Neonatologie ist eine Ganzheitsmedizin des Neugeborenen mit Schwergewicht auf der Umstellung vom intra- zum extrauterinen Leben. In den letzten 50 Jahren konnte in der Schweiz die neonatale Mortalität von 25 auf 3 pro tausend Lebendgeborene gesenkt werden. Die grösste Herausforderung bilden heute extreme Frühgeborene und Kinder mit komplexen Fehlbildungen. Beiden Risikogruppen können wir mit Intensivtherapie zum Überleben verhelfen, bei einzelnen Kindern bleiben jedoch schwere Behinderungen. Daraus ergibt sich ein Bedarf nach Forschung zum besseren Verständnis und zur gezielten Unterstützung der komplexen Entwicklungs- und Wachstumsvorgänge ausserhalb des Mutterleibs, und es kann ein medizinisch-ethisches Dilemma entstehen. Das Swiss Neonatal Network dokumentiert seit 1996 die Ersthospitalisation von Risikoneugeborenen und verfolgt die weitere psychomotorische Entwicklung und Lebensqualität bis ins Schulalter und darüber hinaus.
Diagnostik und Behandlungskonzept bei Hämoptoe
Authors: Franzen Daniel , Schneiter Didier , Pfammatter Thomas , Kohler Malcolm
Published: July 2013

Unter Hämoptoe wird das Aushusten von Blut oder die Blutbeimengung im Sputum verstanden. Die Liste der Differenzialdiagnosen ist breit und hauptsächlich durch die geographische Herkunft des Patienten geprägt. Während eine leichte Hämoptoe in der Regel ambulant abgeklärt werden kann, ist die schwere Hämoptoe ein Notfall und sollte stationär in einem Zentrumsspital behandelt werden. Patienten mit schwerer Hämoptoe sollten dabei durch ein multidisziplinäres Team bestehend aus Pneumologen, Intensivmediziner/Anästhesisten, Interventionellen Radiologen und Thoraxchirurgen beurteilt und behandelt werden. Höchste Priorität kommt der Sicherung der Atemwege und der Gewährleistung des pulmonalen Gasaustausches sowie der Kreislaufstabilisierung zu. Die folgenden Abklärungs- und Behandlungsschritte bei schwerer Hämoptoe, die insbesondere die Computertomographie, Laboranalysen, die Bronchoskopie sowie allenfalls die Bronchialarterien-Embolisation umfassen, werden in Form eines Algorithmus präsentiert und diskutiert.
Trügerisches Bauchgefühl
Authors: Müggler Simon A. , von Babo Michelle , Iseli Sarah M. , Reho Ivano , Giambarba Christian
Published: July 2013

Wir berichten über einen 58-jährigen Patienten mit unspezifischen Unterbauchschmerzen, respiratorischem Versagen und Schock. Nach Ausschluss eines akuten Aortensyndroms und einer massiven Lungenembolie wurde der Patient mit Verdacht auf einen akuten Myokardinfarkt zur Koronarangiographie zugewiesen. Dort zeigte sich eine hochgradige linksseitige Hauptstammstenose, was eine perkutane koronare Intervention erforderte. Es wird auf die Problematik der Akutsituation mit möglichem akutem Aortensyndrom, akutem Koronarsyndrom und massiver Lungenembolie eingegangen. Zudem werden die Schwierigkeiten bei der Erkennung einer linksseitigen Hauptstammstenose im EKG diskutiert.
The ribosome triggers the stringent response by RelA via a highly distorted tRNA
Authors: Agirrezabala Xabier , Fernández Israel S , Kelley Ann C , Cartón David Gil , Ramakrishnan Venki , Valle Mikel
Published: July 2013

The bacterial stringent response links nutrient starvation with the transcriptional control of genes. This process is initiated by the stringent factor RelA, which senses the presence of deacylated tRNA in the ribosome as a symptom of amino‐acid starvation to synthesize the alarmone (p)ppGpp. Here we report a cryo‐EM study of RelA bound to ribosomes bearing cognate, deacylated tRNA in the A‐site. The data show that RelA on the ribosome stabilizes an unusual distorted form of the tRNA, with the acceptor arm making contact with RelA and far from its normal location in the peptidyl transferase centre.
Interaction of smoothened with integrin‐linked kinase in primary cilia mediates Hedgehog signalling
Authors: Barakat Badia , Yu Liang , Lo Camden , Vu Duc , De Luca Elisabetta , Cain Jason E , Martellotto Luciano G , Dedhar Shoukat , Sadler Anthony J , Wang Die , Neil Watkins D , Hannigan Gregory E
Published: July 2013

Here we report that ILK localizes in the mouse primary cilium, a sensory organelle required for signalling by the Hedgehog (Hh) pathway. Genetic or pharmacological inhibition of ILK blocks ciliary accumulation of the Hh pathway effector smoothened (Smo) and suppresses the induction of Gli transcription factor mRNAs by SHh. Conditional deletion of ILK or Smo also inhibits SHh‐driven activation of Gli2 in the embryonic mouse cerebellum. ILK regulation of Hh signalling probably requires the physical interaction of ILK and Smo in the cilium, and we also show selective cilia‐associated interaction of ILK with β‐arrestin, a known mediator of Smo‐dependent signalling.
EndoS2 is a unique and conserved enzyme of serotype M49 group A Streptococcus that hydrolyses N-linked glycans on IgG and α1-acid glycoprotein
Authors: Sjögren Jonathan , Struwe Weston B. , Cosgrave Eoin F. J. , Rudd Pauline M. , Stervander Martin , Allhorn Maria , Hollands Andrew , Nizet Victor , Collin Mattias
Published: July 2013

Many bacteria have evolved ways to interact with glycosylation functions of the immune system of their hosts. Streptococcus pyogenes [GAS (group A Streptococcus)] secretes the enzyme EndoS that cleaves glycans on human IgG and impairs the effector functions of the antibody. The ndoS gene, encoding EndoS, has, until now, been thought to be conserved throughout the serotypes. However, in the present study, we identify EndoS2, an endoglycosidase in serotype M49 GAS strains. We characterized EndoS2 and the corresponding ndoS2 gene using sequencing, bioinformatics, phylogenetic analysis, recombinant expression and LC–MS analysis of glycosidic activity. This revealed that EndoS2 is present exclusively, and highly conserved, in serotype M49 of GAS and is only 37% identical with EndoS. EndoS2 showed endo-β-N-acetylglucosaminidase activity on all N-linked glycans of IgG and on biantennary and sialylated glycans of AGP (α1-acid glycoprotein). The enzyme was found to act only on native IgG and AGP and to be specific for free biantennary glycans with or without terminal sialylation. GAS M49 expression of EndoS2 was monitored in relation to carbohydrates present in the culture medium and was linked to the presence of sucrose. We conclude that EndoS2 is a unique endoglycosidase in serotype M49 and differs from EndoS of other GAS strains by targeting both IgG and AGP. EndoS2 expands the repertoire of GAS effectors that modify key glycosylated molecules of host defence.
Protein kinase D-mediated phosphorylation at Ser99 regulates localization of p21-activated kinase 4
Authors: Bastea Ligia I. , Döppler Heike , Pearce Sarah E. , Durand Nisha , Spratley Samantha J. , Storz Peter
Published: July 2013

PAKs (p21-activated kinases) are effectors of RhoGTPases. PAK4 contributes to regulation of cofilin at the leading edge of migrating cells through activation of LIMK (Lin-11/Isl-1/Mec-3 kinase). PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1). Phosphorylation of PAK4 at Ser99 also mediates binding to 14-3-3 protein, and is required for the formation of a PAK4–LIMK–PKD1 complex that regulates cofilin activity and directed cell migration.
Mycobacterium tuberculosis DNA gyrase possesses two functional GyrA-boxes
Authors: Bouige Aurélie , Darmon Amélie , Piton Jérémie , Roue Mélanie , Petrella Stéphanie , Capton Estelle , Forterre Patrick , Aubry Alexandra , Mayer Claudine
Published: July 2013

In contrast with most bacteria which possess two type II topoisomerases (topoisomerase IV and DNA gyrase), Mycobacterium tuberculosis possesses only one, DNA gyrase, which is functionally a hybrid enzyme. Functional differences between the two type IIA topoisomerases are thought to be specified by a CTD (C-terminal DNA-binding domain), which controls DNA recognition. To explore the molecular mechanism responsible for the hybrid functions of the M. tuberculosis DNA gyrase, we conducted a series of sequence analyses and structural and biochemical experiments with the isolated GyrA CTD and the holoenzyme. Although the CTD displayed a global structure similar to that of bona fide GyrA and ParC paralogues, it harbours a second key motif similar in all respects to that of the conserved GyrA-box sequence motif. Biochemical assays showed that the GyrA-box is responsible for DNA supercoiling, whereas the second GyrA-box-l (GyrA-box-like motif) is responsible for the enhanced decatenation activity, suggesting that the mechanistic originality of M. tuberculosis DNA gyrase depends largely on the particular DNA path around the CTD allowed for by the presence of GyrA-box-l. The results of the present study also provide, through phylogenetic exploration of the entire Corynebacterineae suborder, a new and broader insight into the functional diversity of bacterial type IIA topoisomerases.
A cross-kingdom Nudix enzyme that pre-empts damage in thiamin metabolism
Authors: Goyer Aymeric , Hasnain Ghulam , Frelin Océane , Ralat Maria A. , Gregory Jesse F. , Hanson Andrew D.
Published: July 2013

Genes specifying the thiamin monophosphate phosphatase and adenylated thiazole diphosphatase steps in fungal and plant thiamin biosynthesis remain unknown, as do genes for ThDP (thiamin diphosphate) hydrolysis in thiamin metabolism. A distinctive Nudix domain fused to Tnr3 (thiamin diphosphokinase) in Schizosaccharomyces pombe was evaluated as a candidate for these functions. Comparative genomic analysis predicted a role in thiamin metabolism, not biosynthesis, because free-standing homologues of this Nudix domain occur not only in fungi and plants, but also in proteobacteria (whose thiamin biosynthesis pathway has no adenylated thiazole or thiamin monophosphate hydrolysis steps) and animals (which do not make thiamin). Supporting this prediction, recombinant Tnr3 and its Saccharomyces cerevisiae, Arabidopsis and maize Nudix homologues lacked thiamin monophosphate phosphatase activity, but were active against ThDP, and up to 60-fold more active against diphosphates of the toxic thiamin degradation products oxy- and oxo-thiamin. Deleting the S. cerevisiae Nudix gene (YJR142W) lowered oxythiamin resistance, overexpressing it raised resistance, and expressing its plant or bacterial counterparts restored resistance to the YJR142W deletant. By converting the diphosphates of damaged forms of thiamin into monophosphates, the Tnr3 Nudix domain and its homologues can pre-empt the misincorporation of damaged diphosphates into ThDP-dependent enzymes, and the resulting toxicity.
Dynamics of Gαi1 interaction with type 5 adenylate cyclase reveal the molecular basis for high sensitivity of Gi-mediated inhibition of cAMP production
Authors: Milde Markus , Rinne Andreas , Wunder Frank , Engelhardt Stefan , Bünemann Moritz
Published: July 2013

Many physiological and pathophysiological processes are regulated by cAMP. Different therapies directly or indirectly influence the cellular concentration of this second messenger. A wide variety of receptors either activates or inhibits adenylate cyclases in order to induce proper physiological responses. A key event in this signalling system is the direct and dynamic interaction of Gαi1 subunits with adenylate cyclases. We established a FRET-based assay between G-protein subunits and AC5 (type 5 adenylate cyclase) and monitored receptor-stimulated interactions between Gαi1 and AC5 in single intact cells with high temporal resolution. We observed that FRET between Gαi1 and AC5 developed at much lower concentration of agonist compared with the overall Gi-protein activity resulting in a left-shift of the concentration–response curve by approximately one order of magnitude. Furthermore, Gi1-protein-mediated attenuation of AC5-dependent increases in cAMP occurred at comparable low concentrations of agonist. On analysing the dynamics we found the dissociation of the Gαi1 subunits and AC5 to occur significantly slower than the G-protein deactivation and to be insensitive to RGS4 (regulator of G-protein signalling type 4) expression. This led us to the conclusion that AC5, by binding active Gαi1, interferes with G-protein deactivation and reassembly and thereby might sensitize its own regulation.
The reduction in sigma-promoter recognition flexibility as induced by core RNAP is required for sigma to discern the optimal promoter spacing
Authors: Yeh Hsin-Yi , Hsu Hsiu-Ting , Chen Tsung-Ching , Chung Kuei-Min , Liou Kung-Ming , Chang Ban-Yang
Published: July 2013

Sigma (σ) factors are bacterial transcription initiation factors that direct transcription at cognate promoters. The promoters recognized by primary σ are composed of −10 and −35 consensus elements separated by a spacer of 17±1 bp for optimal activity. However, how the optimal promoter spacing is sensed by the primary σ remains unclear. In the present study, we examined this issue using a transcriptionally active Bacillus subtilis N-terminally truncated σA (SND100-σA). The results of the present study demonstrate that SND100-σA binds specifically to both the −10 and −35 elements of the trnS spacing variants, of which the spacer lengths range from 14 to 21 bp, indicating that simultaneous and specific recognition of promoter −10 and −35 elements is insufficient for primary σ to discern the optimal promoter spacing. Moreover, shortening in length of the flexible linker between the two promoter DNA-binding domains of σA also does not enable SND100-σA to sense the optimal promoter spacing. Efficient recognition of optimal promoter spacing by SND100-σA requires core RNAP (RNA polymerase) which reduces the flexibility of simultaneous and specific binding of SND100-σA to both promoter −10 and −35 elements. Thus the discrimination of optimal promoter spacing by σ is core-dependent.
Genetic and structural validation of Aspergillus fumigatus N-acetylphosphoglucosamine mutase as an antifungal target
Authors: Fang Wenxia , Du Ting , Raimi Olawale G. , Hurtado-Guerrero Ramón , Mariño Karina , Ibrahim Adel F. M. , Albarbarawi Osama , Ferguson Michael A. J. , Jin Cheng , Van Aalten Daan M. F.
Published: July 2013

Aspergillus fumigatus is the causative agent of IA (invasive aspergillosis) in immunocompromised patients. It possesses a cell wall composed of chitin, glucan and galactomannan, polymeric carbohydrates synthesized by processive glycosyltransferases from intracellular sugar nucleotide donors. Here we demonstrate that A. fumigatus possesses an active AfAGM1 (A. fumigatus N-acetylphosphoglucosamine mutase), a key enzyme in the biosynthesis of UDP (uridine diphosphate)–GlcNAc (N-acetylglucosamine), the nucleotide sugar donor for chitin synthesis. A conditional agm1 mutant revealed the gene to be essential. Reduced expression of agm1 resulted in retarded cell growth and altered cell wall ultrastructure and composition. The crystal structure of AfAGM1 revealed an amino acid change in the active site compared with the human enzyme, which could be exploitable in the design of selective inhibitors. AfAGM1 inhibitors were discovered by high-throughput screening, inhibiting the enzyme with IC50s in the low μM range. Together, these data provide a platform for the future development of AfAGM1 inhibitors with antifungal activity.
Long non-coding RNAs and their implications in cancer epigenetics
Authors: Beckedorff Felipe C. , Amaral Murilo Sena , Deocesano-Pereira Carlos , Verjovski-Almeida Sergio
Published: July 2013

LncRNAs (long non-coding RNAs) have emerged as key molecular players in the regulation of gene expression in different biological processes. Their involvement in epigenetic processes includes the recruitment of histone-modifying enzymes and DNA methyltransferases, leading to the establishment of chromatin conformation patterns that ultimately result in the fine control of genes. Some of these genes are related to tumorigenesis and it is well documented that the misregulation of epigenetic marks leads to cancer. In this review, we highlight how some of the lncRNAs implicated in cancer are involved in the epigenetic control of gene expression. While very few lncRNAs have already been identified as players in determining the cancer-survival outcome in a number of different cancer types, for most of the lncRNAs associated with epigenetic regulation only their altered pattern of expression in cancer is demonstrated. Thanks to their tissue-specificity features, lncRNAs have already been proposed as diagnostic markers in specific cancer types. We envision the discovery of a wealth of novel spliced and unspliced intronic lncRNAs involved in epigenetic networks or in highly location-specific epigenetic control, which might be predominantly altered in specific cancer subtypes. We expect that the characterization of new lncRNA (long non-coding RNA)–protein and lncRNA–DNA interactions will contribute to the discovery of potential lncRNA targets for use in therapies against cancer.
Inactivation of the phosphoglucomutase gene pgm in Corynebacterium glutamicum affects cell shape and glycogen metabolism
Authors: Seibold Gerd M. , Eikmanns Bernhard J.
Published: July 2013

In Corynebacterium glutamicum formation of glc-1-P (α-glucose-1-phosphate) from glc-6-P (glucose-6-phosphate) by α-Pgm (phosphoglucomutase) is supposed to be crucial for synthesis of glycogen and the cell wall precursors trehalose and rhamnose. Furthermore, Pgm is probably necessary for glycogen degradation and maltose utilization as glucan phosphorylases of both pathways form glc-1-P. We here show that C. glutamicum possesses at least two Pgm isoenzymes, the cg2800 (pgm) encoded enzyme contributing most to total Pgm activity. By inactivation of pgm we created C. glutamicum IMpgm showing only about 12% Pgm activity when compared to the parental strain. We characterized both strains during cultivation with either glucose or maltose as substrate and observed that (i) the glc-1-P content in the WT (wild-type) and the mutant remained constant independent of the carbon source used, (ii) the glycogen levels in the pgm mutant were lower during growth on glucose and higher during growth on maltose, and (iii) the morphology of the mutant was altered with maltose as a substrate. We conclude that C. glutamicum employs glycogen as carbon capacitor to perform glc-1-P homeostasis in the exponential growth phase and is therefore able to counteract limited Pgm activity for both anabolic and catabolic metabolic pathways.
N-acetyl-seryl-aspartyl-lysyl-proline reduces cardiac collagen cross-linking and inflammation in angiotensin II-induced hypertensive rats
Authors: González Germán E. , Rhaleb Nour-Eddine , Nakagawa Pablo , Liao Tang-Dong , Liu Yunhe , Leung Pablo , Dai Xiangguo , Yang Xiao-Ping , Carretero Oscar A.
Published: July 2013

We have reported previously that Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) reduces fibrosis and inflammation (in macrophages and mast cells). However, it is not known whether Ac-SDKP decreases collagen cross-linking and lymphocyte infiltration; lymphocytes modulate both collagen cross-linking and ECM (extracellular matrix) formation in hypertension. Thus we hypothesized that (i) in AngII (angiotensin II)-induced hypertension, Ac-SDKP prevents increases in cross-linked and total collagen by down-regulating LOX (lysyl oxidase), the enzyme responsible for cross-linking, and (ii) these effects are associated with decreased pro-fibrotic cytokine TGFβ (transforming growth factor β) and the pro-inflammatory transcription factor NF-κB (nuclear factor κB) and CD4+/CD8+ lymphocyte infiltration. We induced hypertension in rats by infusing AngII either alone or combined with Ac-SDKP for 3 weeks. Whereas Ac-SDKP failed to lower BP (blood pressure) or LV (left ventricular) hypertrophy, it did prevent AngII-induced increases in (i) cross-linked and total collagen, (ii) LOX mRNA expression and LOXL1 (LOX-like 1) protein, (iii) TGFβ expression, (iv) nuclear translocation of NF-κB, (v) CD4+/CD8+ lymphocyte infiltration, and (vi) CD68+ macrophages infiltration. In addition, we found a positive correlation between CD4+ infiltration and LOXL1 expression. In conclusion, the effect of Ac-SDKP on collagen cross-linking and total collagen may be due to reduced TGFβ1, LOXL1, and lymphocyte and macrophage infiltration, and its effect on inflammation could be due to lower NF-κB.
Fibulin-2 deficiency attenuates angiotensin II-induced cardiac hypertrophy by reducing transforming growth factor-β signalling
Authors: Zhang Hangxiang , Wu Jing , Dong Hailong , Khan Shaukat A. , Chu Mon-Li , Tsuda Takeshi
Published: July 2013

AngII (angiotensin II) is a potent neurohormone responsible for cardiac hypertrophy, in which TGF (transforming growth factor)-β serves as a principal downstream mediator. We recently found that ablation of fibulin-2 in mice attenuated TGF-β signalling, protected mice against progressive ventricular dysfunction, and significantly reduced the mortality after experimental MI (myocardial infarction). In the present study, we investigated the role of fibulin-2 in AngII-induced TGF-β signalling and subsequent cardiac hypertrophy. We performed chronic subcutaneous infusion of AngII in fibulin-2 null (Fbln2−/−), heterozygous (Fbln2+/−) and WT (wild-type) mice by a mini-osmotic pump. After 4 weeks of subpressor dosage of AngII infusion (0.2 μg/kg of body weight per min), WT mice developed significant hypertrophy, whereas the Fbln2−/− showed no response. In WT, AngII treatment significantly up-regulated mRNAs for fibulin-2, ANP (atrial natriuretic peptide), TGF-β1, Col I (collagen type I), Col III (collagen type III), MMP (matrix metalloproteinase)-2 and MMP-9, and increased the phosphorylation of TGF-β-downstream signalling markers, Smad2, TAK1 (TGF-β-activated kinase 1) and p38 MAPK (mitogen-activated protein kinase), which were all unchanged in AngII-treated Fbln2−/− mice. The Fbln2+/− mice consistently displayed AngII-induced effects intermediate between WT and Fbln2−/−. Pressor dosage of AngII (2 mg/kg of body weight per min) induced significant fibrosis in WT but not in Fbln2−/− mice with comparable hypertension and hypertrophy in both groups. Isolated CFs (cardiac fibroblasts) were treated with AngII, in which direct AngII effects and TGF-β-mediated autocrine effects was observed in WT. The latter effects were totally abolished in Fbln2−/− cells, suggesting that fibulin-2 is essential for AngII-induced TGF-β activation. In conclusion our data indicate that fibulin-2 is essential for AngII-induced TGF-β-mediated cardiac hypertrophy via enhanced TGF-β activation and suggest that fibulin-2 is a potential therapeutic target to inhibit AngII-induced cardiac remodelling.