Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria

Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure–activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth. Optimized compound 27 has an excellent off-target activity profile in erythrocyte lysis and HepG2 assays and is stable in human plasma. This compound is available via the molecular libraries probe production centers network (MLPCN) and is designated ML238.Chemistry and Chemical Biolog

'You can take a horse to water but you can't make it drink': Exploring children's engagement and resistance in family therapy

The final publication is available at Springer via http://dx.doi.org/10.1007/s10591-012-9220-8Children’s engagement and disengagement, adherence and non-adherence, compliance and non-compliance in healthcare have important implications for services. In family therapy mere attendance to the appointments is no guarantee of engaging in the treatment process and as children are not the main initiators of attendance engaging them through the process can be a complex activity for professionals. Through a conversation analysis of naturally occurring family therapy sessions we explore the main discursive strategies that children employ in this context to passively and actively disengage from the therapeutic process and investigate how the therapists manage and attend to this. We note that children competently remove themselves from therapy through passive resistance, active disengagement, and by expressing their autonomy. Analysis reveals that siblings of the constructed ‘problem’ child are given greater liberty in involvement. We conclude by demonstrating how therapists manage the delicate endeavour of including all family members in the process and how engagement and re-engagement are essential for meeting goals and discuss broader implications for healthcare and other settings where children may disengage

Need satisfaction in intergroup contact:A multinational study of pathways toward social change

none43siFinanziamenti esterni a vari co-autoriWhat role does intergroup contact play in promoting support for social change toward greater social equality? Drawing on the needs-based model of reconciliation, we theorized that when inequality between groups is perceived as illegitimate, disadvantaged group members will experience a need for empowerment and advantaged group members a need for acceptance. When intergroup contact satisfies each group's needs, it should result in more mutual support for social change. Using four sets of survey data collected through the Zurich Intergroup Project in 23 countries, we tested several preregistered predictions, derived from the above reasoning, across a large variety of operationalizations. Two studies of disadvantaged groups (Ns = 689 ethnic minority members in Study 1 and 3,382 sexual/gender minorities in Study 2) support the hypothesis that, after accounting for the effects of intergroup contact and perceived illegitimacy, satisfying the need for empowerment (but not acceptance) during contact is positively related to support for social change. Two studies with advantaged groups (Ns = 2,937 ethnic majority members in Study 3 and 4,203 cis-heterosexual individuals in Study 4) showed that, after accounting for illegitimacy and intergroup contact, satisfying the need for acceptance (but also empowerment) is positively related to support for social change. Overall, findings suggest that intergroup contact is compatible with efforts to promote social change when group-specific needs are met. Thus, to encourage support for social change among both disadvantaged and advantaged group members, it is essential that, besides promoting mutual acceptance, intergroup contact interventions also give voice to and empower members of disadvantaged groups.mixedHässler, Tabea; Ullrich, Johannes; Sebben, Simone; Shnabel, Nurit; Bernardino, Michelle; Valdenegro, Daniel; Van Laar, Colette; González, Roberto; Visintin, Emilio Paolo; Tropp, Linda R; Ditlmann, Ruth K; Abrams, Dominic; Aydin, Anna Lisa; Pereira, Adrienne; Selvanathan, Hema Preya; von Zimmermann, Jorina; Lantos, Nóra Anna; Sainz, Mario; Glenz, Andreas; Kende, Anna; Oberpfalzerová, Hana; Bilewicz, Michal; Branković, Marija; Noor, Masi; Pasek, Michael H; Wright, Stephen C; Žeželj, Iris; Kuzawinska, Olga; Maloku, Edona; Otten, Sabine; Gul, Pelin; Bareket, Orly; Corkalo Biruski, Dinka; Mugnol-Ugarte, Luiza; Osin, Evgeny; Baiocco, Roberto; Cook, Jonathan E; Dawood, Maneeza; Droogendyk, Lisa; Loyo, Angélica Herrera; Jelić, Margareta; Kelmendi, Kaltrina; Pistella, JessicaHässler, Tabea; Ullrich, Johannes; Sebben, Simone; Shnabel, Nurit; Bernardino, Michelle; Valdenegro, Daniel; Van Laar, Colette; González, Roberto; Visintin, Emilio Paolo; Tropp, Linda R; Ditlmann, Ruth K; Abrams, Dominic; Aydin, Anna Lisa; Pereira, Adrienne; Selvanathan, Hema Preya; von Zimmermann, Jorina; Lantos, Nóra Anna; Sainz, Mario; Glenz, Andreas; Kende, Anna; Oberpfalzerová, Hana; Bilewicz, Michal; Branković, Marija; Noor, Masi; Pasek, Michael H; Wright, Stephen C; Žeželj, Iris; Kuzawinska, Olga; Maloku, Edona; Otten, Sabine; Gul, Pelin; Bareket, Orly; Corkalo Biruski, Dinka; Mugnol-Ugarte, Luiza; Osin, Evgeny; Baiocco, Roberto; Cook, Jonathan E; Dawood, Maneeza; Droogendyk, Lisa; Loyo, Angélica Herrera; Jelić, Margareta; Kelmendi, Kaltrina; Pistella, Jessic

A large-scale test of the link between intergroup contact and support for social change

Guided by the early findings of social scientists, practitioners have long advocated for greater contact between groups to reduce prejudice and increase social cohesion. Recent work, however, suggests that intergroup contact can undermine support for social change towards greater equality, especially among disadvantaged group members. Using a large and heterogeneous dataset (12,997 individuals from 69 countries), we demonstrate that intergroup contact and support for social change towards greater equality are positively associated among members of advantaged groups (ethnic majorities and cis-heterosexuals) but negatively associated among disadvantaged groups (ethnic minorities and sexual and gender minorities). Specification-curve analysis revealed important variation in the size—and at times, direction—of correlations, depending on how contact and support for social change were measured. This allowed us to identify one type of support for change—willingness to work in solidarity— that is positively associated with intergroup contact among both advantaged and disadvantaged group members

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The European Modern Pollen Database (EMPD) project

Modern pollen samples provide an invaluable research tool for helping to interpret the quaternary fossil pollen record, allowing investigation of the relationship between pollen as the proxy and the environmental parameters such as vegetation, land-use, and climate that the pollen proxy represents. The European Modern Pollen Database (EMPD) is a new initiative within the European Pollen Database (EPD) to establish a publicly accessible repository of modern (surface sample) pollen data. This new database will complement the EPD, which at present holds only fossil sedimentary pollen data. The EMPD is freely available online to the scientific community and currently has information on almost 5,000 pollen samples from throughout the Euro-Siberian and Mediterranean regions, contributed by over 40 individuals and research groups. Here we describe how the EMPD was constructed, the various tables and their fields, problems and errors, quality controls, and continuing efforts to improve the available dat