Monoclonal antibodies as tools in antigen detection assay and vaccine development : design of a sensitive detection test for Brucella bacteria and profiling of the malaria vaccine candidate antigen reticulocyte-binding homolog 2 (PfRH2)

We aimed at identifying immunodominant Brucella antigens for implementation in new detection tools or for subunit vaccine development. In particular, our strategy was to produce Brucella cell surface antigen-specific monoclonal antibodies (mAbs) for the development of an antigen capture assay for the detection of Brucella cells as potential bio threat agents in complex samples. We generated a panel of Brucella lipopolysaccharide (LPS)-specific mAbs by immunising mice with inactivated B. melitensis and B. abortus cells. The mAbs recognised Brucella species with ‘smooth’ LPS independently of the way how the bacterial cells were inactivated. Two mAbs were implemented into a bead-based Luminex assay detecting ‘smooth’ Brucella spp. with species-dependent detection limits of 2 x 102 to 8 x 104 cells per mL. Integration of the Luminex assay into a multiplex format enabled simultaneous detection of Brucella spp. and three other bio threat agents within a single sample. The developed Luminex assay may be applied for the detection of whole Brucella cells both in natural Brucella outbreak and in bioterrorism attack scenarios. We also tried to generate mAbs against Brucella cell surface proteins from mice immunised with inactivated whole Brucella cells. While serum antibody responses against both LPS and protein antigens were seen in Western blotting analyses, attempts to generate protein-specific mAbs failed, most likely due to the immunodominant nature of the LPS. Western blot analyses with Brucella lysate also identified antibodies against some immunodominant Brucella proteins in the serum of cattle naturally infected with Brucella spp., however, identification of the recognised proteins with a Brucella-specific peptide microarray failed. In a second part of the thesis we aimed at evaluating the potential of the Plasmodium falciparum reticulocyte-binding homolog 2 (PfRH2) present in the rhoptries as a malaria blood stage vaccine antigen. We produced PfRH2-specific mAbs by immunising mice with the 40kDa receptor-binding domain of PfRH2. The PfRH2-specific mAbs cross-reacted with the natural PfRH2 protein present in schizont stage parasites and showed a rhoptry-characteristic staining pattern in immunofluorescence microscopy. However when evaluated in functional in vitro and in vivo assays PfRH2 specific mAbs showed no inhibitory effect on erythrocyte invasion. Furthermore, the invasion-inhibitory effect of mAbs specific for the cysteine-rich protective antigen (PfCyRPA) was not enhanced by PfRH2-specific mAbs

Psychological Challenges of Unification - Selected Results and Thoughts on Korea

A number of early warning signs for the break-down of a political system like North Korea are presented, inspired by recent research in psychological science. Taking post-unification Germany as an exemplary case, the times soon after the turnabout and the mid2000s are considered in light of our own research. The focus is on the new challenges people were confronted with, which resources helped them to cope with strain and stress, and what all this meant for well-being. Concerning the 1990s, key drivers of behavior and its change were the changed institutions that resulted in rather quick adaptation to the new rules. Nevertheless, personal resources such as self-efficacy, gained under the old system, made a difference. In the 2000s, it was the uncertainties about life planning, rooted in the unification aftermath and effects of globalization and economic jeopardy, which shaped behavior. When confronted with challenges, people typically responded by active engagement, and if supported by internal control beliefs this helped to protect well-being in spite of the difficult situation. Under especially dire circumstances, however, disengagement was positive because it spares resources for alternative action. For the situation on the Korean Peninsula the German research results made plausible that policy interventions can use many entry points in the system of coping with social change, from opportunities to personal skills, to ease the challenges of living in a new country. Further, it demonstrates that a unification scenario inspired by the German model would require acculturation in both parts of the country, not only in the North. And finally, one has to consider lasting deficiencies in crucial agency factors due to growing up in an environment characterized by scarcity of adequate living conditions for large segments of the population

Current Trends in Research on Behavioral Development in the Federal Republic of Germany

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The state and perspective of developmental psychology in the Federal Republic of Germany is analyzed with respect to (a) professional education, (b) resources for research, (c) actual fields of research, and (d) media of professional communication. Current trends of research were investigated by a combination of multi-category content analyses of national (and international) journal publications, and survey data with respect to research interests and planned studies of German developmentalists. Included among the main trends are: (a) an increasing emphasis on longitudinal studies, sometimes combined with short-term interventions; (b) a growing interest in studies representative of natural conditions; (c) although still relatively rare, some of the studies employ a developmental perspective not only for persons but also for relations between persons and changes in environmental factors; (d) areas of heaviest concentration are cognitive development, social as well as personality development, with a trend towards more molar concepts of action-regulating systems instead of small-range models; (e) a growing number of studies on youth and adolescence; (f) new efforts towards a systematic elaboration of the application perspectives of developmental psychology. Professional education as well as research in developmental psychology was highly influenced by a 6-year program from the Volkswagen foundation. As a result, one could observe an increase in quantity as well as an improvement in quality both of teaching and research. Two further steps are now being planned: (a) a post-graduate program, the first one in German psychology, will start in 1983; (b) further efforts to broaden symmetric international communication and cooperation will be undertaken

Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms : revival of an old drug

BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. CONCLUSIONSIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launche

Contributions of behaviour genetics to the identification of effects of ecological contexts on the development of children and adolescents. A state-of-the-art report

Ein zentrales Problem der Erforschung von Kontexteffekten auf die menschliche Entwicklung besteht darin, dass Effekte der Umwelt methodisch nur schlecht von Effekten der Erbanlagen zu trennen sind. Verhaltensgenetische Studien bieten hierfür Lösungsansätze. Der vorliegende Beitrag gibt einen Überblick über verhaltensgenetische Konzepte, die das Verständnis von Kontextwirkungen auf die psychische Entwicklung erweitert haben (geteilte und nicht geteilte Umwelt, Genom-Umwelt-Korrelation und Genom-Umwelt-Interaktion). Anschließend werden verhaltensgenetische Untersuchungsdesigns vorgestellt und sechs wichtige Befunde der Verhaltensgenetik über Kontexteffekte zusammengefasst. So zeigen Studien, dass die von den Kindern nicht geteilte Umwelt im Mittel wichtiger für die Entwicklung ist als die geteilte Umwelt, dass Umweltmerkmale - wie Elternverhalten - genetisch beeinflusst sind, und dass Zusammenhänge zwischen Umwelt- und Verhaltensmerkmalen häufig von genetischen Dispositionen beeinflusst werden. Abschließend werden Schlussfolgerungen für die künftige Forschung zu Kontexteffekten auf die Entwicklung abgeleitet. (DIPF/Orig.)Research on the role of ecological contexts in human development is challenged by the fact that environmental effects cannot easily be separated from genetic effects. However, behaviour genetics provides some solutions to that problem. The present article starts with an overview about theoretical concepts from behaviour genetics that have enlarged the understanding of context effects on psychological development (shared and nonshared environment, genome-environment-correlations, and genome-environment-interactions). Then, we discuss behaviour genetic research designs and six important results regarding context effects. For example, studies show that effects of the nonshared environment on psychological development are, on average, larger than effects of the shared environment. Further, characteristics of the children\u27s environment, such as parental behaviour, are influenced by genes. The covariance between environmental characteristics and behavioural measures is, in part, based on genetic dispositions. Finally, conclusions are drawn regarding future search for context effects on psychological development. (DIPF/Orig

Development as action in changing contexts: perspectives from six countries

"In diesem Artikel werden fünf aktuelle Beiträge besprochen, die sich empirisch mit der Interaktion zwischen wandelnden sozio-historischen Kontexten und der individuellen Anpassung und Entwicklung auseinander setzen. Die Beiträge von John Bynner, Rand Conger und Mitarbeitern, Cigndem Kagitcibasi, Jungsik Kim und Mitarbeitern sowie von Ingrid Schoon werden auf dem Hintergrund eines Modells zur Entwicklung im sozialen Wandel diskutiert. Es wird argumentiert, dass Forschung zum sozialen Wandel den politischen und sozialen Kontext berücksichtigen muss und dass es dabei notwendig ist, die für die Interaktion zwischen Makro und Mikro stehenden Bedingungen zu identifizieren und zu untersuchen. Solche Forschung ist dann nicht nur geeignet um die Disziplin als solche zu bereichern oder um das Modell der Entwicklung im Kontext voranzutreiben. Sie ist auch von Relevanz um sozialpolitische Interventionen in Zeiten des raschen sozialen Wandels zu begründen." (Autorenreferat)"This paper reviews five recent contributions that empirically investigate the interaction between changing socio-historical contexts and individual adaptation and development. The contributions by John Bynner, Rand Conger and colleagues, Cigdem Kagitcibasi, Jungsik Kim and colleagues and Ingrid Schoon are discussed against the backdrop of a generic model of social change and human development. It is argued that research on social change has to consider the larger political and social context and needs to identify and to study conditions that represent the processes of macro-micro-interaction. Such research will not only enrich the scientific inquiry in this field and promote theorizing about development-in-context, but also is of relevance for social policies in times of rapid social change." (author's abstract

Pubertal maturation and affective symptoms in adolescence and adulthood: evidence from a prospective birth cohort

The higher prevalence of affective symptoms among women compared to men emerges in adolescence, and it has been associated with pubertal maturation. However, it remains unclear whether pubertal timing has long-term influences on affective symptoms. Using data from the British 1946 birth cohort, we investigated whether pubertal timing was associated with affective symptoms over the life course, distinguishing those with symptoms in adolescence only, symptoms in adulthood only, and symptoms in both adolescence and adulthood. In females, there was no evidence that early pubertal maturation was a risk factor for affective symptoms. However, those with particularly late menarche (≥15 years) showed a lower risk of adult-onset affective symptoms (OR = 0.54, 95% CI: 0.31, 0.95). This effect of late pubertal timing was not explained by a range of socio-behavioural factors. In contrast, in males, late pubertal timing was associated with increased risk of adolescent-onset affective symptoms that tracked into adulthood (OR = 2.10, 95% CI: 1.44, 3.06). This effect was partly explained by low pre-pubertal BMI. Sex-specific effects of pubertal timing on the long-term risk of affective symptoms might be due to different effects of gonadal hormonal on the CNS, as well as different social experiences during puberty

Between Here and There: Patterns and Predictors of Transnationalism among Three Immigrant Groups in Germany

The increasingly global world is giving rise to the new form of immigrant movement called transnationalism, characterized by immigrants’ close ties with both host and home nations as well as frequent trips between the two countries. Despite lively theoretical discussion of transnationalism there is very little empirical research on patterns and predictors of transnational migration. The current study investigates predictors of group and individual variability in transnationalism within three largest immigrant groups in Germany: ethnic Germans, Russian Jews, and Turks. Impacts of context of exit and entry, demographic variables, and sociocultural retention variables on transnationalism are investigated. Results show that ethnic groups are indeed different in the frequency of visiting the country of origin, and demonstrate the importance of cultural and identification variables in predicting betweenindividual variability in transnationalism

Effekte der Akupunktur auf die metabolisch induzierte Vasodilatation bei chronischen Rauchern - Untersuchung mittels Venenverschlussplethysmographie

Background: Chronic smoking is the primary risk factor for the development of atherosclerosis. The early adverse events of smoking are reflected by a functional impairment of vasomotor function known to precede and predict the formation of vascular lesion. We investigated the effects of acupuncture on flow mediated vasodilation (FMD) as a measure of vascular function in chronic smokers. Methods and Results: Otherwise healthy male chronic smokers (n=20) were compared with healthy volunteers (n=11). All patients received 5 sessions of systemic acupuncture over 3 weeks. FMD was determined by venous occlusion plethysmography. Soluble P-selectin, plasminogen activator inhibitor 1 (PAI-1) and high sensitive CRP levels were measured on each visit. In chronic smokers FMD was impaired when compared to controls. In addition, plasma P-selectin and PAI-1 levels were found to be higher compared to controls. 5 consecutive acupuncture sessions significantly improved impaired FMD of forearm resistance vesselsin chronic smokers. This was associated with significant reduction of enhanced soluble P-selectin and plasma PAI-1 antigen levels. Conclusions: The results demonstrate for the first time that acupuncture improves impaired flow mediated vasodilation of the forearm vasculature in otherwise healthy chronic smokers. Acupuncture may be a therapeutic tool to restore flow mediated vasodilation in chronic smokers with impaired vascular function

"Für Politik relevant" bedeutet mehr als nur "Forschung mit Anwendungsbezug": Kommentar zu Guy Bodenmann

'Der Kommentar zu Bodenmanns Beitrag versucht an Beispielen zu zeigen, dass es mehr als korrelativer Evidenz zum Zusammenhang von familiären Risikobedingungen und problematischen kindlichen Verhaltensweisen bedarf, wenn man als Forscher politische Entscheidungen zur Planung von Interventionen beeinflussen will. Zuvorderst muss eine klare Ursache-Wirkungs-Beziehung mit geeigneten Designs belegt werden. Weiterhin sind Informationen über die Veränderbarkeit der Risikobedingung, etwa die von Bodenmann angeführte elterliche Sensitivität erforderlich, man benötigt Kenntnisse zu möglichen Schwelleneffekten mit Blick auf das Problemverhalten, Abschätzungen der Kostenwürdigkeit, sowie Einsichten in mögliche Nebeneffekte der Intervention und alternativer Ziele und Maßnahmen.' (Autorenreferat)'In this commentary on Bodenmann's paper, the author tries to exemplify that in order to be relevant to the formulation of social policies, researchers need to offer more than correlative evidence on potential family antecedents of children's behaviour that are deemed problematic for the development of competence. Rather, a clear cause-effect relation has to be established via adequate design. Moreover, policy makers need information on the malleability of the antecedent condition, such as parental sensitivity mentioned by Bodenmann, knowledge about potential thresholds for effective intervention, cost-effect estimates, and insights into potential side effects and alternative solutions to the targets and measures originally suggested.' (author's abstract