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    Drosophila Ror is a nervous system-specific co-receptor for Wnt ligands 

    Ripp, Caroline; Loth, Julia; Petrova, Iveta; Linnemannstöns, Karen; Ulepic, Monique; Fradkin, Lee; Noordermeer, Jasprien; Wodarz, Andreas
    Biology Open 2018; 7(11): Art. bio033001
    Wnt ligands are secreted glycoproteins that control many developmental processes and are crucial for homeostasis of numerous tissues in the adult organism. Signal transduction of Wnts involves the binding of Wnts to receptor complexes at the surface of target cells. These receptor complexes are commonly formed between a member of the Frizzled family of seven-pass transmembrane proteins and a co-receptor, which is usually a single-pass transmembrane protein. Among these co-receptors are several with structural homology to receptor tyrosine kinases, including Ror, PTK7, Ryk and MUSK. In vertebrates, Ror-2 and PTK7 are important regulators of planar cell polarity (PCP). By contrast, PCP phenotypes were not reported for mutations in off-track (otk) and off-track2 (otk2), encoding the Drosophila orthologs of PTK7. Here we show that Drosophila Ror is expressed in the nervous system and localizes to the plasma membrane of perikarya and neurites. A null allele of Ror is homozygous viable and fertile, does not display PCP phenotypes and interacts genetically with mutations in otk and otk2 We show that Ror binds specifically to Wingless (Wg), Wnt4 and Wnt5 and also to Frizzled2 (Fz2) and Otk. Our findings establish Drosophila Ror as a Wnt co-receptor expressed in the nervous system.
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    Gain-of-Function (GOF) Mutant p53 as Actionable Therapeutic Target 

    Schulz-Heddergott, Ramona; Moll, Ute M.
    Cancers 2018; 10(6)
    p53 missense mutant alleles are present in nearly 40% of all human tumors. Such mutated alleles generate aberrant proteins that not only lose their tumor-suppressive functions but also frequently act as driver oncogenes, which promote malignant progression, invasion, metastasis, and chemoresistance, leading to reduced survival in patients and mice. Notably, these oncogenic gain-of-function (GOF) missense mutant p53 proteins (mutp53) are constitutively and tumor-specific stabilised. This stabilisation is one key pre-requisite for their GOF and is largely due to mutp53 protection from the E3 ubiquitin ligases Mdm2 and CHIP by the HSP90/HDAC6 chaperone machinery. Recent mouse models provide convincing evidence that tumors with highly stabilized GOF mutp53 proteins depend on them for growth, maintenance, and metastasis, thus creating exploitable tumor-specific vulnerabilities that markedly increase lifespan if intercepted. This identifies mutp53 as a promising cancer-specific drug target. This review discusses direct mutp53 protein-targeting drug strategies that are currently being developed at various preclinical levels.
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    Antenatal care services and its implications for vital and health outcomes of children: evidence from 193 surveys in 69 low-income and middle-income countries. 

    Kuhnt, Jana; Vollmer, Sebastian
    BMJ open 2017; 7(11): Art. e017122
    OBJECTIVES: Antenatal care (ANC) is an essential part of primary healthcare and its provision has expanded worldwide. There is limited evidence of large-scale cross-country studies on the impact of ANC offered to pregnant women on child health outcomes. We investigate the association of ANC in low-income and middle-income countries with short- and long-term mortality and nutritional child outcomes. SETTING: We used nationally representative health and welfare data from 193 Demographic and Health Surveys conducted between 1990 and 2013 from 69 low-income and middle-income countries for women of reproductive age (15-49 years), their children and their respective household. PARTICIPANTS: The analytical sample consisted of 752 635 observations for neonatal mortality, 574 675 observations for infant mortality, 400 426 observations for low birth weight, 501 484 observations for stunting and 512 424 observations for underweight. MAIN OUTCOMES AND MEASURES: Outcome variables are neonatal and infant mortality, low birth weight, stunting and underweight. RESULTS: At least one ANC visit was associated with a 1.04% points reduced probability of neonatal mortality and a 1.07% points lower probability of infant mortality. Having at least four ANC visits and having at least once seen a skilled provider reduced the probability by an additional 0.56% and 0.42% points, respectively. At least one ANC visit is associated with a 3.82% points reduced probability of giving birth to a low birth weight baby and a 4.11 and 3.26% points reduced stunting and underweight probability. Having at least four ANC visits and at least once seen a skilled provider reduced the probability by an additional 2.83%, 1.41% and 1.90% points, respectively. CONCLUSIONS: The currently existing and accessed ANC services in low-income and middle-income countries are directly associated with improved birth outcomes and longer-term reductions of child mortality and malnourishment.
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    Levels and trends of childhood undernutrition by wealth and education according to a Composite Index of Anthropometric Failure: evidence from 146 Demographic and Health Surveys from 39 countries 

    Vollmer, Sebastian; Harttgen, Kenneth; Kupka, Roland; Subramanian, S. V.
    BMJ Global Health 2017; 2(2): Art. e000206
    Background Governments have endorsed global targets to reduce childhood undernutrition as part of the Sustainable Development Goals. Understanding the socioeconomic differences in childhood undernutrition has the potential to be helpful for targeting policy to reach these goals. Methods We specify a logistic regression model with the Composite Index of Anthropometric Failure (CIAF) as the outcome and indicator variables for wealth quartiles, maternal education categories and a set of covariates as explanatory variables. Wealth and education variables are interacted with a period indicator for 1990–2000 compared with 2001–2014 to observe differences over time. Based on these regressions we calculate predicted CIAF prevalence by wealth and education categories and over time. Results The sample included 146 surveys from 39 low-income and lower-middle-income countries with an overall sample size of 533 217 children. CIAF prevalence was 47.5% in 1990–2000, and it declined to 42.6% in 2001–2014. In 1990–2000 the CIAF prevalence of children with mothers with less than primary education was 31 percentage points higher than for mothers with secondary or higher education. This difference slightly decreased to 27 percentage points in 2001–2014. The difference in predicted CIAF prevalence of children from the highest and lowest wealth quartiles was 21 percentage points and did not change over time. Conclusions We find evidence for persistent and even increasing socioeconomic inequalities in childhood undernutrition, which underlines the importance of previous calls for equity-driven approaches targeting the most vulnerable to reduce childhood malnutrition.
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    Panya: Economies of Deception and the Discontinuities of Indentured Labour Recruitment and the Slave Trade, Nigeria and Fernando Pó, 1890s–1940s 

    Martino, Enrique
    African Economic History 2016; 44(1) p.91-129
    In the first half of the twentieth century, most of Fernando Pó’s contract workers came from societies in southeastern Nigeria which had been heavily impacted by the transatlantic and internal slave trades. These contract workers were recruited by a new generation of labor recruiters, dispatched covertly by Spanish imperial employers, through a form of kidnapping known as panya. Panya was the largest labor smuggling and trafficking network in colonial West Africa, bringing tens of thousands of migrants to long and obligatory contracts on Fernando Pó. In contrast to scholars who have interpreted this history as a holdover from the pre-colonial period, this article argues that panya arose from the contractual order of Spanish imperial rule. Extensive archival research reveals the voices of those caught in the warp of post-abolition colonial labor regimes, in order to rethink the passage from the pre-colonial slave trade to imperialism within West African history. Using a series of vivid and precise petitions submitted by those who found themselves on the island of Fernando Pó, the article shows how these sources contain the potential to reconceptualize the disjunctures between enslavement in the slave trade and the recruitment of contract labor.
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    Dash-peonage: the contradictions of debt bondage in the colonial plantations of Fernando Pó 

    Martino, Enrique
    Africa 2017; 87(1) p.53-78
    Dash in pidgin English means an ancillary gift to an exchange. What happened when the dash became attached to the indentured labour contracts that the Spanish Empire brought from Cuba to their last colony, Spanish Guinea? On the island of Fernando Pó, which came to be almost wholly populated by Nigerian labour migrants, the conditional gift in the form of a large wage advance produced a particularly intense contradiction. In the historiography of unfree labour, the excess wage advance is thought to create conditions for the perpetuation of bondage through debt. However, in imperial contexts, the wage advance did not generate compliance and immobility; exactly the opposite – it produced unprecedented waves of further escalation and dispersed flight. The dash was pushed up by workers themselves and relayed by informal recruiters. Together they turned this lynchpin of indentured labour and debt peonage into a counter-practice that almost led to the collapse of the plantations in the 1950s. The trajectories of the dash led to a more pointed version of the foundational thesis of global labour history: namely, that it was actually free labour, not unfree labour, that was incompatible with labour scarcity-ridden imperial capitalism.
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