bluuebunny/crossref_metadata_2025 huggingface dataset:
Die Bedeutung individueller und familiärer Ressourcen für die Krankheitsbewältigung von Müttern mit neurodermitiskranken Kindern
Authors: Tröster Heinrich , Aktas Maren
Published: June 2015

Zusammenfassung. Theoretischer Hintergrund: Familienstresstheorien lassen erwarten, dass die Auswirkungen krankheitspezifischer Stressoren auf die Familie durch individuelle Bewältigungskompetenzen der Mütter und durch die Funktionsfähigkeit der Familie moderiert werden. Fragestellung: Überprüft wurde der Beitrag des Schweregrades der Neurodermitis des Kindes, des krankheitsspezifischen Copings der Mütter und der Funktionsfähigkeit der Familie zur Vorhersage der Belastung von Müttern mit neurodermitiskranken Kindern. Methode: An einer Stichprobe von 45 Müttern mit neurodermitiskranken Kindern im Alter von 5 bis 82 Monaten wurde die mütterliche Belastung, das krankheitsspezifische Coping der Mütter sowie die familiäre Funktionsfähigkeit erfasst. Ergebnisse: Die mütterliche Belastung war unabhängig von objektiven Indikatoren des Schweregrades der Neurodermitis. Als bedeutsame Prädiktoren der mütterlichen Belastung erwiesen sich die von den Müttern wahrgenommenen krankheitsspezifischen Beeinträchtigungen des Kindes sowie das mütterliche Coping. Die familiäre Funktionsfähigkeit leistete darüber hinaus keinen signifikanten Beitrag zur Aufklärung der Varianz der mütterlichen Belastung. Schlussfolgerung: Die krankheitsspezifischen Bewältigungskompetenzen der Mütter haben Einfluss darauf, inwieweit die Anforderungen, die sich aus der Neurodermitis des Kindes ergeben, zur Belastung der Mütter führen. Die in unserer Studie erfassten familiären Funktionsbereiche beinhalten offenbar nicht die spezifischen Ressourcen für die Krankheitsverarbeitung in Familien mit neurodermitiskranken Kindern.
Ekelempfindlichkeit: ein Vulnerabilitätsfaktor für essgestörtes Verhalten
Authors: Schienle Anne , Walter Bertram , Schäfer Axel , Stark Rudolf , Vaitl Dieter
Published: June 2015

Zusammenfassung. Theoretischer Hintergrund: Eine erhöhte Ekelempfindlichkeit wird als Vulnerabilitätsfaktor für Essstörungen diskutiert. Fragestellung: Gibt es einen Zusammenhang zwischen habituellen und aktuellen Ekelreaktionen von Frauen und deren Neigung zu essgestörtem Verhalten? Methode: Ausprägungen von 85 Frauen in einem Essstörungs-Inventar (ESI, Diehl & Staufenbiel, 1994 ) und einem Fragebogen zur Erfassung der Ekelempfindlichkeit (FEE, Schienle et al., 2002 ) wurden korreliert. Außerdem wurden die emotionalen Einstufungen für Bilder der Kategorien “Ekel“, “Angst“ und “Neutral“ mit den ESI-Werten korreliert. Ergebnisse: Die Korrelation zwischen ESI und FEE betrug r = .41; positive Zusammenhänge ergaben sich auch zwischen ESI-Werten und Ekeleinstufungen der Ekel- (r = .34), Angst- (r = .33) und Neutralbilder (r = .41). Schlussfolgerung: Dieses Ergebnis weist auf die mögliche Rolle einer verstärkten Ekelneigung für die Entstehung und Aufrechterhaltung von Essstörungen hin.
Aspekte emotionaler Kompetenz bei sozial ängstlichen Kindern
Authors: Melfsen Siebke , Florin† Irmela
Published: June 2015

Zusammenfassung. Theoretischer Hintergrund: Es gibt Hinweise, dass eine Dysregulation der emotionalen Entwicklung im Zusammenhang mit der Ätiologie von Angststörungen stehen könnte. Fragestellung: Ziel unserer Studien war es, Aspekte der emotionalen Kompetenz bei sozial ängstlichen Kindern und ihren Müttern zu untersuchen. Methode: Es nahmen 50 sozial ängstliche und 25 sozial nicht ängstliche Kinder sowie ihre Mütter an drei experimentellen Studien teil. Sie wurden aufgefordert, mimische Emotionsausdrücke zu zeigen. In einer Leistungssituation und einer lustigen Situation wurde ihre spontane Mimik untersucht. In der dritten Studie sollten emotionale Gesichtsausdrücke klassifiziert werden. Ergebnisse: Die sozial ängstlichen Kinder zeigten weniger genaue willentliche mimische Emotionsausdrücke. Sie zeigten einen verringerten spontanen mimischen Emotionsausdruck von Freude, nicht jedoch von Ärger. Beim Klassifizieren benötigten sie längere Reaktionszeiten und deuteten häufiger Emotionen in neutrale Gesichter. Schlussfolgerung: Die Befunde weisen auf Defizite in der emotionalen Kompetenz bei sozial ängstlichen Kindern hin. Sollten sich die Ergebnisse replizieren lassen, sollte dies Bedeutung für die Therapie sozialer Ängste im Kindesalter haben.
Der Inkongruenzfragebogen (INK)
Authors: Grosse Holtforth Martin , Grawe Klaus
Published: June 2015

Zusammenfassung. Theoretischer Hintergrund: Menschen streben nach Bedürfnisbefriedigung durch die Umsetzung ihrer Ziele. Motivationale Inkongruenz bezeichnet die unzureichende Umsetzung motivationaler Ziele. Fragestellung: Konstruktion, teststatistische und Validitätsprüfung der Inkongruenzfragebögen (INK und K-INK). Methode: Der INK wurde unter Verwendung der Iteminhalte des FAMOS ( Grosse Holtforth & Grawe, 2000 ) konstruiert und in verschiedenen Stichproben (N = 1077) zusammen mit anderen Fragebogenmaßen vorgegeben. Eine Kurzversion (K-INK) wurde aus den trennschärfsten Items konstruiert. Ergebnisse: Hauptachsenanalysen reproduzieren die Skalenstruktur des FAMOS größtenteils und trennen Annäherungs- und Vermeidungszielskalen. Reliabilitätswerte für INK und K-INK sind größtenteils befriedigend. Inkongruenzwerte sind bei Patienten stärker ausgeprägt als bei Kontrollpersonen und korrelieren hoch mit Symptombelastung, Depressivität, Lebenszufriedenheit, Wohlbefinden und Neurotizismus, hingegen gering mit FAMOS-Werten. Schlussfolgerung: INK und K-INK erweisen sich als geeignete Messinstrumente zur Inkongruenzmessung in Forschung und Praxis.
Kreativ? Innovativ? Effizient? Defizient?
Authors: Hautzinger Martin
Published: June 2015

Zusammenfassung. Anhand der sorgfältig begutachteten Veröffentlichungen der letzten vier Jahre in der Zeitschrift für Klinische Psychologie und Psychotherapie werden Schwerpunkte und Schwachpunkte, Vielfalt und Einseitigkeit, Bewährung und Mängel, Effizienz und Defizite unseres Fachs deutlich. Diese Übersicht mündet in Anregungen und Wünsche, die sowohl in der Forschung als auch in den Veröffentlichungen Berücksichtigung finden sollten.
Zur Psychotherapie sozialer Ängste: Kognitive Verhaltenstherapie im Vergleich zu einem kombiniert ressourcenorientierten Vorgehen
Authors: Willutzki Ulrike , Neumann Barbara , Haas Hilde , Koban Christoph , Schulte Dietmar
Published: June 2015

Zusammenfassung. Theoretischer Hintergrund: Im Rahmen einer Interpretation sozialer Ängste als Handlungsregulationsproblem wird die Relevanz von Ressourcen in der Psychotherapie herausgearbeitet. Fragestellung: Kann das Therapieangebot für Patienten mit sozialen Ängsten durch Fokussierung der Ressourcen der Person verbessert werden? Methode: In einer randomisierten kontrollierten Interventionsstudie für 83 Patienten mit sozialen Ängsten wird ein kombiniert kognitiv-verhaltenstherapeutisch/ressourcen-orientiertes Vorgehen (KROT) mit einem fokal kognitiv-verhaltenstherapeutischen Angebot (KVT) verglichen. Ergebnisse: Bei insgesamt im Vergleich zu anderen Therapiestudien befriedigenden Ergebnissen profitiert die KROT-Gruppe sowohl auf der Ebene der sozialphobischen Symptomatik wie auch der psychischen Belastung stärker. Dies schlägt sich in höheren Effektstärken nieder (für die sozialphobische Symptomatik: KVT = .86, KROT = 1.39; psychische Belastung insgesamt: KVT = .84, KROT = 1.18). Schlussfolgerungen: Der Therapieerfolg bei sozialer Phobie kann durch die Kombination kognitiv-verhaltenstherapeutischer Ansätze mit ressourcenorientierten Elementen verbessert werden
Zur Neuropsychologie und Neurophysiologie der Anorexia nervosa
Authors: Murphy Roy
Published: June 2015

Zusammenfassung. Theoretischer Hintergrund: Konvergierende neurowissenschaftliche Befunde zur Anorexia nervosa deuten darauf hin, dass Veränderungen im Zentralnervensystem mit Störungen des Essverhaltens assoziiert sein können. Fragestellung und Methode: Es soll ein Überblick über ausgewählte empirische Befunde aus den Bereichen Neuroanatomie, Neurophysiologie und Neuropsychologie gegeben werden. Ergebnisse und Schlussfolgerungen: Trotz der teilweise heterogenen Befundlage belegen die Ergebnisse, dass bei der Anorexie strukturelle und funktionelle cerebrale Veränderungen vorliegen können, denen möglicherweise eine Rolle bei der Genese und Aufrechterhaltung der Erkrankung zukommt.
Symptomatik bei kriegs- und folterüberlebenden Flüchtlingen, mit und ohne Psychotherapie
Authors: Birck Angelika
Published: June 2015

Zusammenfassung. Ins Behandlungszentrum für Folteropfer Berlin (BZFO) kommen hauptsächlich Flüchtlinge. Fragestellung: In einer explorativen Studie wurden Patienten nach ihrer Aufnahme (t1) und etwa ein Jahr später (t2) untersucht. Patienten, die psychotherapeutisch behandelt wurden und für die wir Stellungnahmen schrieben (N = 21) und solche, für die wir ausschließlich diagnostisch tätig wurden (N = 33), wurden verglichen. Methode: Die Datenerhebung erfolgte mit Fragebogen (IES-R, PDS, SCL-90-R, SUD). Ergebnisse: Die Ergebnisse verdeutlichen eine sehr hohe Symptombelastung beider Gruppen zu beiden Untersuchungszeitpunkten, die Symptomatik hatte sich trotz Therapie nicht verändert. Ursachen dafür können eine subobtimale Therapie sein, aber auch die rechtliche Verknüpfung von Aufenthaltssituation und Erkrankung, außerdem kann die jahrelang andauernde Abschiebebedrohung eine Besserung behindern.
Berufsbezogene Einstellungen, Ressourcen und Risikomerkmale im Therapieverlauf:
Authors: Beutel Manfred E. , Zwerenz Rüdiger , Kayser Egon , Schattenburg Lothar , Knickenberg Rudolf J.
Published: June 2015

Zusammenfassung. Hintergrund. Das Fehlen standardisierter Messverfahren ist hinderlich für die psychotherapeutische Diagnostik und Bearbeitung berufsbezogener Belastungen und Konflikte. Der AVEM (Arbeitsbezogenes Verhaltens- und Erlebensmuster) erfasst Selbstbeschreibungen berufsbezogener Einstellungen, Bewältigungsressourcen und Risikomerkmale differenziert und ökonomisch, wurde allerdings an nicht- klinischen Stichproben (Lehrerinnen, Führungskräfte) entwickelt. Fragestellung: Überprüfung der Eignung des AVEM für psychisch und psychosomatisch Kranke. Methode: 644 Patientinnen und Patienten wurden bei Aufnahme zur stationären psychosomatischen Rehabilitation, Entlassung und 3-Monatskatamnese (N = 329) untersucht. Ergebnisse: Faktorenstruktur und Reliabilität wurden repliziert. Korrelationen mit weiteren Selbstbeschreibungsverfahren ergaben Validitätshinweise. Selbsteinschätzungen berufsbezogener Ressourcen veränderten sich während der Therapie in Richtung auf die Normstichprobe. Schlussfolgerungen: Es handelt sich um ein diagnostisch vielversprechendes Verfahren; prädiktive Validität und komplexere Auswertungsstrategien bedürfen weiterer Überprüfung.
Zusammenhänge zwischen Veränderungen in verschiedenen Funktionsbereichen von schizophren Erkrankten während der Durchführung sozialer Fertigkeitstrainings
Authors: Lächler Marc , Roder Volker
Published: June 2015

Zusammenfassung. Theoretischer Hintergrund: Auf Grund einer Übersicht bisheriger Befunde schlugen Green und Nuechterlein (1999) ein Modell vor, welches das Zusammenwirken zwischen verschiedenen Funktionsbereichen schizophren Erkrankter beschreibt. Fragestellung: Die vorliegende explorative Studie untersucht, ob sich Zusammenhänge zwischen Veränderungen im kognitiven und sozialen Bereich sowie der Symptomatik schizophren Erkrankter während der Durchführung sozialer Fertigkeitstrainings ergeben und inwiefern diese dem von Green und Nuechterlein vorgeschlagenen Modell entsprechen. Methode: 80 Patienten, die an einem sozialen Fertigkeitstraining teilgenommen hatten, wurden in die Auswertung einbezogen. Als hauptsächliche Auswertungsmethode wurde der “typologische“ Ansatz zur Veränderungsmessung von Schöttke et al. (1993) verwendet. Ergebnisse: Signifikante Zusammenhänge ergaben sich zwischen den Veränderungen in der Aufmerksamkeitsleistung, der Negativsymptomatik und dem sozialen Funktionsniveau. Die Veränderungen in der Positivsymptomatik zeigten sich von den Veränderungen in den restlichen Bereichen als unabhängig. Schlussfolgerungen: Die Ergebnisse entsprechen weitgehend den bisherigen Befunden und in diesem Sinne dem von Green & Nuechterlein vorgeschlagenen Modell. Eine mögliche Bedeutung dieser Ergebnisse für die differenzielle Indikation in der psychosozialen Behandlung schizophren Erkrankter wird diskutiert.
Validierung der deutschen Version des Attachment Style Questionnaire (ASQ) bei Personen mit und ohne psychiatrische Diagnosen
Authors: Hexel Martina
Published: June 2015

Zusammenfassung. Theoretischer Hintergrund: Der Attachment Style Questionnaire (ASQ) erfasst Selbsteinschätzungen in Bezug auf Bindungsstile. Fragestellung: Die deutschsprachige Version des ASQ wurde validiert. Methode: Zur Überprüfung der konvergenten Validität wurden die 20-Item Toronto Alexithymie Skala (TAS-20), das Screening für somatoforme Störungen (SOMS) und das Parental Bonding Instrument (PBI) vorgegeben, sowie Gruppenvergleiche und eine Clusteranalyse durchgeführt. Ergebnisse: In Übereinstimmung mit der englischsprachigen Version des ASQ führt auch bei der deutschsprachigen Version eine Faktorenanalyse zu einer 5-Faktorenlösung, die insgesamt 49,4% der Gesamtvarianz erklärt. Hoch signifikante Gruppenunterschiede zwischen Personen mit und ohne psychiatrische Diagnose konnten in den fünf Skalen festgestellt werden. Schlussfolgerungen: Die deutschsprachige Version des ASQ stellt insgesamt ein brauchbares Instrument für die Identifikation von Bindungsverhalten dar.
Experimentelle Überprüfung des Fragebogens zur Erfassung der Ekelempfindlichkeit (FEE)
Authors: Rohrmann Sonja , Schienle Anne , Hodapp Volker , Netter Petra
Published: June 2015

Zusammenfassung. Theoretischer Hintergrund: Die experimentelle Überprüfung des neu entwickelten Fragebogens zur Erfassung der Ekelempfindlichkeit (FEE) stand noch aus. Fragestellung: Unterscheiden sich gering und stark ekelempfindliche Personen in ihren Reaktionen auf einen ekelinduzierenden Film? Methode: 170 Studenten wurden anhand der Gesamtskala (FEEges) und der Subskala Tod (FEETod) des FEE als gering bzw. stark ekelempfindlich (E-/E+) klassifiziert. Ihnen wurde ein neutraler und ein ekelinduzierender Filmclip gezeigt und ihre physiologischen, subjektiven, mimischen und Copingreaktionen hierauf erhoben. Ergebnisse: E+ klassifiziert nach FEETod, nicht jedoch nach FEEges wiesen stärkere physiologische, subjektive und mimische Ekelreaktionen auf als E-; E+ zeigten unabhängig von der Art der Klassifikation ein weniger defensives Copingverhalten als E-. Schlussfolgerung: Die Klassifikation nach FEETod, nicht jedoch nach FEEges führt bei der spezifischen Ekelinduktion zu differentiellen Ekelreaktionen. Aus differentialpsychologischen und klinischen Überlegungen heraus ist die Erfassung bereichspezifischer Ekelempfindlichkeit sinnvoll.
Eine Kurzversion des Tinnitus-Fragebogens von Goebel und Hiller (1998)
Authors: Leibetseder Max , Unterrainer Josef , Greimel Karoline Verena , Köller Thomas
Published: June 2015

Zusammenfassung.Theoretischer Hintergrund: Der Tinnitus-Fragebogen von Goebel und Hiller (1998) misst Tinnitus-Belastung durch sechs teilweise korrelierte Faktoren. Diese beruhen unter anderem auf Konstrukten der Informationsverarbeitung, wie irrationale Überzeugungen, Übergeneralisierungen und Attitüden der Hilflosigkeit. Fragestellung: In dieser Arbeit wurde eine Reanalyse des Tinnitus-Fragebogens unter Berücksichtigung seiner Item-Charakteristika vorgenommen. Methode: Der Tinnitus-Fragebogen wurde einer Stichprobe von 153 betroffener Personen vorgelegt und nach den Kriterien der klassischen Testtheorie geprüft. Ergebnisse: In einer Faktorenanalyse zeigte sich ein Faktor der Tinnitus-Belastung, welcher eine zufriedenstellende Reliabilität aufweist und signifikant mit konstruktnahen Merkmalen wie Depression, körperliches Allgemeinbefinden und Kontrollüberzeugungen korreliert. Schlussfolgerungen: Die Ergebnisse weisen die Kurzversion des Tinnitus-Fragebogens als ein den psychometrischen Testkriterien entsprechendes Instrument zur Messung tinnitusbezogener Beeinträchtigungen aus.
Toward a Person × Situation Model of Selective Exposure
Authors: Kim Jinhee , Kim Jung-Hyun , Seo Mihye
Published: June 2015

The present study attempted to predict selective exposure to media messages as a function of personality and situation, which has rarely been examined in prior relevant research. Employing a quasi-experimental method, the interplay between prevailing perceived threat from the economic crisis that started in 2008 and each of the two personality types when dealing with threat – repression and sensitization – was examined to predict online news selection behavior, as unobtrusively recorded. A significant interaction between perceived threat and sensitization tendency was obtained for both the selection of financial crisis-related news and avoidance of financial crisis-unrelated news. The implications of this exclusive pattern of online news selection behavior are discussed.
Attitudes in Context
Authors: von Sikorski Christian , Schierl Thomas
Published: June 2015

The stereotypical media coverage of persons with physical disabilities (PWDs) has been repeatedly criticized, because biased depictions of PWDs can negatively affect nondisabled recipients’ attitudinal evaluations of PWDs. However, it remains unclear how the superordinate context of disability, which is frequently used by journalists to depict PWDs in the media – or other contexts (e.g., sports) – affect recipients’ attitudes toward those PWDs portrayed in the media. Potential context effects were analyzed with the help of two experiments (between-subjects design). In Study 1, nondisabled participants (N = 97) were randomly assigned to four groups. The context was manipulated by subliminally (30 ms) exposing participants to different textual primes of disability, sports, politics, and no prime (control group). Participants subsequently evaluated a visually depicted PWD (arm amputation). In Study 2, nondisabled participants (N = 63) were randomly assigned to three groups, and they read an illustrated print article (the same picture as in Study 1 was used). The context was manipulated with the help of specific news cues (disability, sports, politics), while the rest of the article remained unchanged. In both studies, the context of disability significantly lowered participants’ evaluations of the PWD. In contrast, sports – in both studies – had a systematically positive impact on participants’ attitudes toward the PWD. Furthermore, the general acceptance of PWDs in society was perceived to be more positive with sports cues in Study 2. Implications for the media coverage of PWDs are discussed.
Contribution of Demographics, Sociological Factors, and Media Usage to Verbal Aggressiveness
Authors: Glascock Jack
Published: June 2015

Given the increasing relevance of verbal aggression in today’s society, the goal of this study was to assess the relative contributions of potential demographic and sociological factors. Emerging adults were surveyed, and the data were analyzed using correlations and hierarchical regression. While television viewing, video game playing, and music listening were positively correlated with verbal aggression, only (rap) music listening remained significant when demographic and other sociological influences were factored in. Overall, the hierarchical regression analysis found religiosity, parental and peer influence, quality of neighborhood, sex, and media usage (listening to rap music) to be significant contributors to verbal aggression among emerging adults. Male participants reported more verbally aggressive behavior than women, and African Americans reported more verbal aggression than White respondents. While media usage seems to play a significant, but relatively small role, other demographic and sociological factors such as gender, neighborhood, religion, peers, and parents appear to be major contributors in the development of verbal aggression among emerging adults.
Optimization of methods for the genetic modification of human T cells
Authors: Bilal Mahmood Y , Vacaflores Aldo , Houtman Jon CD
Published: June 2015

CD4+ T cells are not only critical in the fight against parasitic, bacterial and viral infections, but are also involved in many autoimmune and pathological disorders. Studies of protein function in human T cells are confined to techniques such as RNA interference (RNAi) owing to ethical reasons and relative simplicity of these methods. However, introduction of RNAi or genes into primary human T cells is often hampered by toxic effects from transfection or transduction methods that yield cell numbers inadequate for downstream assays. Additionally, the efficiency of recombinant DNA expression is frequently low because of multiple factors including efficacy of the method and strength of the targeting RNAs. Here, we describe detailed protocols that will aid in the study of primary human CD4+ T cells. First, we describe a method for development of effective microRNA/shRNAs using available online algorithms. Second, we illustrate an optimized protocol for high efficacy retroviral or lentiviral transduction of human T‐cell lines. Importantly, we demonstrate that activated primary human CD4+ T cells can be transduced efficiently with lentiviruses, with a highly activated population of T cells receiving the largest number of copies of integrated DNA. We also illustrate a method for efficient lentiviral transduction of hard‐to‐transduce un‐activated primary human CD4+ T cells. These protocols will significantly assist in understanding the activation and function of human T cells and will ultimately aid in the development or improvement of current drugs that target human CD4+ T cells.
Prmt5 is a regulator of muscle stem cell expansion in adult mice
Authors: Zhang Ting , Günther Stefan , Looso Mario , Künne Carsten , Krüger Marcus , Kim Johnny , Zhou Yonggang , Braun Thomas
Published: June 2015

Skeletal muscle stem cells (MuSC), also called satellite cells, are indispensable for maintenance and regeneration of adult skeletal muscles. Yet, a comprehensive picture of the regulatory events controlling the fate of MuSC is missing. Here, we determine the proteome of MuSC to design a loss-of-function screen, and identify 120 genes important for MuSC function including the arginine methyltransferase Prmt5. MuSC-specific inactivation of Prmt5 in adult mice prevents expansion of MuSC, abolishes long-term MuSC maintenance and abrogates skeletal muscle regeneration. Interestingly, Prmt5 is dispensable for proliferation and differentiation of Pax7+ myogenic progenitor cells during mouse embryonic development, indicating significant differences between embryonic and adult myogenesis. Mechanistic studies reveal that Prmt5 controls proliferation of adult MuSC by direct epigenetic silencing of the cell cycle inhibitor p21. We reason that Prmt5 generates a poised state that keeps MuSC in a standby mode, thus allowing rapid MuSC amplification under disease conditions.
A negative feedback loop controls NMDA receptor function in cortical interneurons via neuregulin 2/ErbB4 signalling
Authors: Vullhorst Detlef , Mitchell Robert M. , Keating Carolyn , Roychowdhury Swagata , Karavanova Irina , Tao-Cheng Jung-Hwa , Buonanno Andres
Published: June 2015

The neuregulin receptor ErbB4 is an important modulator of GABAergic interneurons and neural network synchronization. However, little is known about the endogenous ligands that engage ErbB4, the neural processes that activate them or their direct downstream targets. Here we demonstrate, in cultured neurons and in acute slices, that the NMDA receptor is both effector and target of neuregulin 2 (NRG2)/ErbB4 signalling in cortical interneurons. Interneurons co-express ErbB4 and NRG2, and pro-NRG2 accumulates on cell bodies atop subsurface cisternae. NMDA receptor activation rapidly triggers shedding of the signalling-competent NRG2 extracellular domain. In turn, NRG2 promotes ErbB4 association with GluN2B-containing NMDA receptors, followed by rapid internalization of surface receptors and potent downregulation of NMDA but not AMPA receptor currents. These effects occur selectively in ErbB4-positive interneurons and not in ErbB4-negative pyramidal neurons. Our findings reveal an intimate reciprocal relationship between ErbB4 and NMDA receptors with possible implications for the modulation of cortical microcircuits associated with cognitive deficits in psychiatric disorders.
Platelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex
Authors: Poulter Natalie S. , Pollitt Alice Y. , Davies Amy , Malinova Dessislava , Nash Gerard B. , Hannon Mike J. , Pikramenou Zoe , Rappoport Joshua Z. , Hartwig John H. , Owen Dylan M. , Thrasher Adrian J. , Watson Stephen P. , Thomas Steven G.
Published: June 2015

The actin nodule is a novel F-actin structure present in platelets during early spreading. However, only limited detail is known regarding nodule organization and function. Here we use electron microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterize the structural organization and signalling pathways associated with nodule formation. Nodules are composed of up to four actin-rich structures linked together by actin bundles. They are enriched in the adhesion-related proteins talin and vinculin, have a central core of tyrosine phosphorylated proteins and are depleted of integrins at the plasma membrane. Nodule formation is dependent on Wiskott–Aldrich syndrome protein (WASp) and the ARP2/3 complex. WASp−/− mouse blood displays impaired platelet aggregate formation at arteriolar shear rates. We propose actin nodules are platelet podosome-related structures required for platelet–platelet interaction and their absence contributes to the bleeding diathesis of Wiskott–Aldrich syndrome.
Graphitic carbon nitride nanosheet electrode-based high-performance ionic actuator
Authors: Wu Guan , Hu Ying , Liu Yang , Zhao Jingjing , Chen Xueli , Whoehling Vincent , Plesse Cédric , Nguyen Giao T. M. , Vidal Frédéric , Chen Wei
Published: June 2015

Ionic actuators have attracted attention due to their remarkably large strain under low-voltage stimulation. Because actuation performance is mainly dominated by the electrochemical and electromechanical processes of the electrode layer, the electrode material and structure are crucial. Here, we report a graphitic carbon nitride nanosheet electrode-based ionic actuator that displays high electrochemical activity and electromechanical conversion abilities, including large specific capacitance (259.4 F g−1) with ionic liquid as the electrolyte, fast actuation response (0.5±0.03% in 300 ms), large electromechanical strain (0.93±0.03%) and high actuation stability (100,000 cycles) under 3 V. The key to the high performance lies in the hierarchical pore structure with dominant size <2 nm, optimal pyridinic nitrogen active sites (6.78%) and effective conductivity (382 S m−1) of the electrode. Our study represents an important step towards artificial muscle technology in which heteroatom modulation in electrodes plays an important role in promoting electrochemical actuation performance.
Identification of new susceptibility loci for IgA nephropathy in Han Chinese
Authors: Li Ming , Foo Jia-Nee , Wang Jin-Quan , Low Hui-Qi , Tang Xue-Qing , Toh Kai-Yee , Yin Pei-Ran , Khor Chiea-Chuen , Goh Yu-Fen , Irwan Ishak D. , Xu Ri-Cong , Andiappan Anand K. , Bei Jin-Xin , Rotzschke Olaf , Chen Meng-Hua , Cheng Ching-Yu , Sun Liang-Dan , Jiang Geng-Ru , Wong Tien-Yin , Lin Hong-Li , Aung Tin , Liao Yun-Hua , Saw Seang-Mei , Ye Kun , Ebstein Richard P. , Chen Qin-Kai , Shi Wei , Chew Soo-Hong , Chen Jian , Zhang Fu-Ren , Li Sheng-Ping , Xu Gang , Shyong Tai E. , Wang Li , Chen Nan , Zhang Xue-Jun , Zeng Yi-Xin , Zhang Hong , Liu Zhi-Hong , Yu Xue-Qing , Liu Jian-Jun
Published: June 2015

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10−10), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10−9) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10−9), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10−19), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10−19; rs12716641, P=9.53 × 10−9; rs9314614, P=4.25 × 10−9, multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
Direct observation of TALE protein dynamics reveals a two-state search mechanism
Authors: Cuculis Luke , Abil Zhanar , Zhao Huimin , Schroeder Charles M.
Published: June 2015

Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins for which the fundamental mechanisms governing the search process are not fully understood. Here we use single-molecule techniques to directly observe TALE search dynamics along DNA templates. We find that TALE proteins are capable of rapid diffusion along DNA using a combination of sliding and hopping behaviour, which suggests that the TALE search process is governed in part by facilitated diffusion. We also observe that TALE proteins exhibit two distinct modes of action during the search process—a search state and a recognition state—facilitated by different subdomains in monomeric TALE proteins. Using TALE truncation mutants, we further demonstrate that the N-terminal region of TALEs is required for the initial non-specific binding and subsequent rapid search along DNA, whereas the central repeat domain is required for transitioning into the site-specific recognition state.
Chemical reaction mechanisms in solution from brute force computational Arrhenius plots
Authors: Kazemi Masoud , Åqvist Johan
Published: June 2015

Decomposition of activation free energies of chemical reactions, into enthalpic and entropic components, can provide invaluable signatures of mechanistic pathways both in solution and in enzymes. Owing to the large number of degrees of freedom involved in such condensed-phase reactions, the extensive configurational sampling needed for reliable entropy estimates is still beyond the scope of quantum chemical calculations. Here we show, for the hydrolytic deamination of cytidine and dihydrocytidine in water, how direct computer simulations of the temperature dependence of free energy profiles can be used to extract very accurate thermodynamic activation parameters. The simulations are based on empirical valence bond models, and we demonstrate that the energetics obtained is insensitive to whether these are calibrated by quantum mechanical calculations or experimental data. The thermodynamic activation parameters are in remarkable agreement with experiment results and allow discrimination among alternative mechanisms, as well as rationalization of their different activation enthalpies and entropies.
‘I still don’t know diddly’: a longitudinal qualitative study of patients’ knowledge and distress while undergoing evaluation of incidental pulmonary nodules
Authors: Sullivan Donald R , Golden Sara E , Ganzini Linda , Hansen Lissi , Slatore Christopher G
Published: June 2015

Background:

Hundreds of thousands of incidental pulmonary nodules are detected annually in the United States, and this number will increase with the implementation of lung cancer screening. The lengthy period for active pulmonary nodule surveillance, often several years, is unique among cancer regimens. The psychosocial impact of longitudinal incidental nodule follow-up, however, has not been described.

Aims:

We sought to evaluate the psychosocial impact of longitudinal follow-up of incidental nodule detection on patients.

Methods:

Veterans who participated in our previous study had yearly follow-up qualitative interviews coinciding with repeat chest imaging. We used conventional content analysis to explore their knowledge of nodules and the follow-up plan, and their distress.

Results:

Seventeen and six veterans completed the year one and year two interviews, respectively. Over time, most patients continued to have inadequate knowledge of pulmonary nodules and the nodule follow-up plan. They desired and appreciated more information directly from their primary care provider, particularly about their lung cancer risk. Distress diminished over time for most patients, but it increased around the time of follow-up imaging for some, and a small number reported severe distress.

Conclusions:

In settings in which pulmonary nodules are commonly detected, including lung cancer screening programmes, resources to optimise patient-centred communication strategies that improve patients’ knowledge and reduce distress should be developed.
Nuclear accumulation of CDH1 mRNA in hepatocellular carcinoma cells
Authors: Ghafoory S , Mehrabi A , Hafezi M , Cheng X , Breitkopf-Heinlein K , Hick M , Huichalaf M , Herbel V , Saffari A , Wölfl S
Published: June 2015

Expression of E-cadherin has a central role in maintaining epithelial morphology. In solid tumors, reduction of E-cadherin results in disruption of intercellular contacts. Consequently, cells lose adhesive properties and gain more invasive mesenchymal properties. Nevertheless, the mechanism of E-cadherin regulation is not completely elucidated. Here we analyzed the distribution of E-cadherin expression at the cell level in human hepatocellular carcinoma, in which human liver paraffin blocks from 25 hepatocellular carcinoma patients were prepared from cancerous (CA) and noncancerous areas (NCA). In situ hybridization (ISH) was performed to detect E-cadherin and hypoxia-induced factor-1α (HIF1α) mRNAs and immunohistochemistry to stain E-cadherin protein. In parallel, RNA was extracted from CA and NCA, and E-cadherin and HIF1α were quantified by quantitative reverse transcription PCR. ISH revealed abundant E-cadherin mRNA in nuclei of hepatocellular carcinoma cells (HCCs), whereas immunohistochemistry showed depletion of E-cadherin protein from these areas. In sections of NCA, E-cadherin mRNA was also found in the cytosol, and E-cadherin protein was detected on the membrane of cells. Experiments in cell lines confirmed E-cadherin mRNA in nuclei of cells negative for E-cadherin protein. HIF1α expression is elevated in CAs, which is associated with a clear cytosolic staining for this mRNA. Our results demonstrate that E-caderhin mRNA is selectively retained in nuclei of HCCs, whereas other mRNAs are still exported, suggesting that translocation of E-cadherin mRNA from nuclei to cytoplasm has a role in regulating E-cadherin protein levels during epithelial mesenchymal transition.
Real-time and simultaneous monitoring of the phosphorylation and enhanced interaction of p53 and XPC acidic domains with the TFIIH p62 subunit
Authors: Okuda M , Nishimura Y
Published: June 2015

Posttranslational modifications have critical roles in diverse biological processes through interactions. Tumor-suppressor protein p53 and nucleotide excision repair factor XPC each contain an acidic region, termed the acidic transactivation domain (TAD) and acidic fragment (AF), respectively, that binds to the pleckstrin homology (PH) domain of the p62 subunit of the transcription factor TFIIH. Human p53-TAD contains seven serine and two threonine residues, all of which can be phosphorylated. Similarly, XPC-AF contains six serine and two threonine residues, of which Thr117, Ser122 and Ser129 have been reported as phosphorylation sites in vivo, although their phosphorylation roles are unknown. Phosphorylation of Ser46 and Thr55 of p53-TAD increases its binding ability; however, the role of XPC-AF phosphorylation remains elusive. Here we describe a system for real-time and simultaneous monitoring of the phosphorylation and p62-PH affinity of p53-TAD and XPC-AF using nuclear magnetic resonance (NMR) spectroscopy. Unexpectedly, among seven reported kinases that presumably phosphorylate Ser46 and/or Thr55 of p53-TAD, only two specific and high-efficiency enzymes were identified: JNK2α2 for Ser46 and GRK5 for Thr55. During interaction with p62-PH, four different affinity complexes resulting from various phosphorylation states of p53-TAD by the kinases were identified. The kinetics of the site-specific phosphorylation reaction of p53-TAD and its affinity for p62-PH were monitored in real-time using the NMR system. Isothermic calorimetry showed that phosphorylation of Ser129 of XPC-AF increases binding to p62-PH. Although CK2 was predicted to phosphorylate Ser122, Ser129 and Ser140 from its sequence context, it specifically and efficiently phosphorylated only Ser129. Simultaneous monitoring of the phosphorylation and augmentation in p62-PH binding identified a key residue of p62-PH for contacting phosphorylated Ser129. In summary, we have established an NMR system for real-time and simultaneous monitoring of site-specific phosphorylation and enhancement of affinity between phosphorylation domains and their target. The system is also applicable to other posttranslational modifications.
Compensatory angiogenesis and tumor refractoriness
Authors: Gacche R N
Published: June 2015

Since the establishment of tumor angiogenesis as a therapeutic target, an excitement in developing the anti-angiogenic agents was resulted in tailoring a humanized monoclonal antibody (Bevacizumab) against vascular endothelial growth factor (VEGF): a key factor in recruiting angiogenesis. The past three decades’ research in the area of angiogenesis also invented a series of novel and effective anti-angiogenic agents targeting the VEGF signaling axis. Despite the demonstrable clinical benefits of anti-angiogenic therapy, the preclinical and clinical data of the current therapeutic settings clearly indicate the transient efficacy, restoration of tumor progression and aggressive recurrence of tumor invasion after the withdrawal of anti-angiogenic therapy. Therefore, the impact of this therapeutic regime on improving overall survival of patients has been disappointing in clinic. The recent advances in pathophysiology of tumor angiogenesis and related molecular and cellular underpinnings attributed the conspiracy of compensatory angiogenic pathways in conferring evasive and intrinsic tumor resistance to anti-angiogenic agents. The understandings of how these pathways functionally cross-talk for sustaining tumor angiogenesis during VEGF blockade is essential and perhaps may act as a basic prerequisite for designing novel therapeutic strategies to combat the growing arrogance of tumors toward anti-angiogenic agents. The present review offers a discourse on major compensatory angiogenic pathways operating at cellular and molecular levels and their attributes with resistance to anti-angiogenic agents along with strategic opinions on future setting in targeting tumor angiogenesis.
Mutations of the functional ARH1 allele in tumors from ARH1 heterozygous mice and cells affect ARH1 catalytic activity, cell proliferation and tumorigenesis
Authors: Kato J , Vekhter D , Heath J , Zhu J , Barbieri J T , Moss J
Published: June 2015

ADP-ribosylation results from transfer of the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD) to an acceptor with ADP-ribose-acceptor content determined by the activities of ADP-ribosyltransferases, which modify the acceptor, and ADP-ribose-acceptor hydrolase (ARH), which cleave the ADP-ribose-acceptor bond. ARH1 was discovered as an ADP-ribose(arginine)protein hydrolase. Previously, we showed that ARH1-knockout and ARH1 heterozygous mice spontaneously developed tumors. Further, ARH1-knockout and ARH1 heterozygous mouse embryonic fibroblasts (MEFs) produced tumors when injected into nude mice. In tumors arising in ARH1 heterozygous mice and MEFs, we found both loss of heterozygosity (LOH) of the ARH1 gene and ARH1 gene mutations. In the present report, we found that these mutant ARH1 genes encode proteins with reduced ARH1 enzymatic activity. Moreover, MEFs transformed with ARH1 mutant genes exhibiting different levels of ARH1 activity showed altered rates of proliferation, anchorage-independent colony growth in soft agar, and tumorigenesis in nude mice. MEFs transformed with the wild-type (WT) gene, but expressing low levels of hydrolase activity were also tumorigenic. However, transformation with the WT gene was less likely to yield tumors than transformation with a mutant gene exhibiting similar hydrolase activity. Thus, control of protein-ADP-ribosylation by ARH1 is critical for tumorigenesis. In the human cancer database, LOH and mutations of the ARH1 gene were observed. Further, ARH1 gene mutations were located in exons 3 and 4, comparable to exons 2 and 3 of the murine ARH1 gene, which comprise the catalytic site. Thus, human ARH1 gene mutations similar to their murine counterparts may be involved in human cancers.
The infection of turkeys and chickens by reassortants derived from pandemic H1N1 2009 and avian H9N2 influenza viruses
Authors: Sun Honglei , Kong Weili , Liu Litao , Qu Yi , Li Chong , Shen Ye , Zhou Yu , Wang Yu , Wu Sizhe , Pu Juan , Liu Jinhua , Sun Yipeng
Published: June 2015

Outbreaks of pandemic H1N1 2009 (pH1N1) in turkeys have been reported in several countries. Co-infection of pH1N1 and avian H9N2 influenza viruses in turkeys provide the opportunity for their reassortment and novel reassortant viruses might further be transmitted to other avian species. However, virulence and transmission of those reassortant viruses in poultry remain unclear. In the present study, we generated 16 single-gene reassortant influenza viruses including eight reassortants on the pH1N1 background by individual replacement with a corresponding gene segment from H9N2 and eight reassortants on the H9N2 background replaced individually with corresponding gene from pH1N1 and characterized reassortants viruses in turkeys and chickens. We found that the pH1N1 virus dramatically increased its infectivity and transmissibility in turkeys and chickens after introducing any gene (except for PB2) from H9N2 virus and H9N2 virus acquired single gene (except for HA) of pH1N1 almost did not influence its replication and transmission in turkeys and chickens. Additionally, 13 reassortant viruses transmitted from turkeys to chickens. Our results indicate that turkeys and chickens are susceptible to pH1N1-H9N2 reassortant viruses and mixing breeding of different avian species would facilitate the transmission of these reassortant viruses.
Placement of oppositely charged aminoacids at a polypeptide termini determines the voltage-controlled braking of polymer transport through nanometer-scale pores
Authors: Asandei Alina , Chinappi Mauro , Lee Jong-kook , Ho Seo Chang , Mereuta Loredana , Park Yoonkyung , Luchian Tudor
Published: June 2015

Protein and solid-state nanometer-scale pores are being developed for the detection, analysis and manipulation of single molecules. In the simplest embodiment, the entry of a molecule into a nanopore causes a reduction in the latter’s ionic conductance. The ionic current blockade depth and residence time have been shown to provide detailed information on the size, adsorbed charge and other properties of molecules. Here we describe the use of the nanopore formed by Staphylococcus aureus α-hemolysin and polypeptides with oppositely charged segments at the N- and C-termini to increase both the polypeptide capture rate and mean residence time of them in the pore, regardless of the polarity of the applied electrostatic potential. The technique provides the means to improve the signal to noise of single molecule nanopore-based measurements.
Automated Detection of Leakage in Fluorescein Angiography Images with Application to Malarial Retinopathy
Authors: Zhao Yitian , J. C. MacCormick Ian , G. Parry David , Leach Sophie , A. V. Beare Nicholas , P. Harding Simon , Zheng Yalin
Published: June 2015

The detection and assessment of leakage in retinal fluorescein angiogram images is important for the management of a wide range of retinal diseases. We have developed a framework that can automatically detect three types of leakage (large focal, punctate focal and vessel segment leakage) and validated it on images from patients with malarial retinopathy. This framework comprises three steps: vessel segmentation, saliency feature generation and leakage detection. We tested the effectiveness of this framework by applying it to images from 20 patients with large focal leak, 10 patients with punctate focal leak and 5,846 vessel segments from 10 patients with vessel leakage. The sensitivity in detecting large focal, punctate focal and vessel segment leakage are 95%, 82% and 81%, respectively, when compared to manual annotation by expert human observers. Our framework has the potential to become a powerful new tool for studying malarial retinopathy and other conditions involving retinal leakage.
Carrier type inversion in quasi-free standing graphene: studies of local electronic and structural properties
Authors: Melios Christos , Panchal Vishal , Giusca Cristina E. , Strupiński Włodek , Silva S. Ravi P. , Kazakova Olga
Published: June 2015

We investigate the local surface potential and Raman characteristics of as-grown and ex-situ hydrogen intercalated quasi-free standing graphene on 4H-SiC(0001) grown by chemical vapor deposition. Upon intercalation, transport measurements reveal a change in the carrier type from n- to p-type, accompanied by a more than three-fold increase in carrier mobility, up to μh ≈ 4540 cm2 V−1 s−1. On a local scale, Kelvin probe force microscopy provides a complete and detailed map of the surface potential distribution of graphene domains of different thicknesses. Rearrangement of graphene layers upon intercalation to (n + 1)LG, where n is the number of graphene layers (LG) before intercalation, is demonstrated. This is accompanied by a significant increase in the work function of the graphene after the H2-intercalation, which confirms the change of majority carriers from electrons to holes. Raman spectroscopy and mapping corroborate surface potential studies.
The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-γ in colitis
Authors: Sato Akira , Kayama Hisako , Shojima Kensaku , Matsumoto Shinji , Koyama Hirofumi , Minami Yasuhiro , Nojima Satoshi , Morii Eiichi , Honda Hiroaki , Takeda Kiyoshi , Kikuchi Akira
Published: June 2015

Wnt5a, which regulates various cellular functions in Wnt signaling, is involved in inflammatory responses, however the mechanism is not well understood. We examined the role of Wnt5a signaling in intestinal immunity using conditional knockout mice for Wnt5a and its receptor Ror2. Removing Wnt5a or Ror2 in adult mice suppressed dextran sodium sulfate (DSS)-induced colitis. It also attenuated the DSS-dependent increase in inflammatory cytokine production and decreased interferon-γ (IFN-γ)-producing CD4+ Th1 cell numbers in the colon. Wnt5a was highly expressed in stromal fibroblasts in ulcerative lesions in the DSS-treated mice and inflammatory bowel disease patients. Dendritic cells (DCs) isolated from the colon of Wnt5a and Ror2 deficient mice reduced the ability to differentiate naïve CD4+ T cells to IFN-γ-producing CD4+ Th1 cells. In vitro experiments demonstrated that the Wnt5a-Ror2 signaling axis augmented the DCs priming effect of IFN-γ, leading to enhanced lipopolysaccharide (LPS)-induced interleukin (IL)-12 expression. Taken together, these results suggest that Wnt5a promotes IFN-γ signaling, leading to IL-12 expression in DCs and thereby inducing Th1 differentiation in colitis.