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Background: Buruli ulcer (BU), one of 17 neglected tropical diseases, is a debilitating skin and soft tissue infection caused by Mycobacterium ulcerans. In tropical Africa, changes in land use and proximity to water have been associated with the disease. This study presents the first analysis of BU at the village level in southwestern Ghana, where prevalence rates are among the highest globally, and explores fine and medium-scale associations with land cover by comparing patterns both within BU clusters and surrounding landscapes., Methodology/principal Findings: We obtained 339 hospital-confirmed BU cases in southwestern Ghana between 2007 and 2010. The clusters of BU were identified using spatial scan statistics and the percentages of six land cover classes were calculated based on Landsat and Rapid Eye imagery for each of 154 villages/towns. The association between BU prevalence and each land cover class was calculated using negative binomial regression models. We found that older people had a significantly higher risk for BU after considering population age structure. BU cases were positively associated with the higher percentage of water and grassland surrounding each village, but negatively associated with the percent of urban. The results also showed that BU was clustered in areas with high percentage of mining activity, suggesting that water and mining play an important and potentially interactive role in BU occurrence., Conclusions/significance: Our study highlights the importance of multiple land use changes along the Offin River, particularly mining and agriculture, which might be associated with BU disease in southwestern Ghana. Our study is the first to use both medium- and high-resolution imagery to assess these changes. We also show that older populations (≥ 60 y) appear to be at higher risk of BU disease than children, once BU data were weighted by population age structures.

The present study investigates the attitudes of older drivers and road safety measures with a particular focus on self-serving evaluations. Driving capacity is considered here as an indicator of awareness of age-related changes that may lead to a higher risk of self-stereotyping, motivating self-serving evaluations with advancing age. In order to test this notion, we used the perceived distance between one's chronological age and the age assigned to the social categories of "older driver" and "old person" as an indicator of age-group dissociation or identification, respectively. Self-serving evaluations were expected depending on the distance between chronological and subjective age estimates. In addition to this, we tested gender and age effects on the specific evaluations. A sample of 350 participants aged 19-88 completed an online questionnaire on negative and positive stereotypes about older drivers and road safety measures. Results indicated in general a more positive than negative view of older drivers; approval with measures to increase road safety by regulating older drivers was comparatively low. Female participants tended to agree more with negative stereotypes and regulative measures than male participants. Regression analyses revealed as well that increasing chronological age was associated with less agreement with negative stereotypes and measures for road safety. Differences between chronological age and subjective age estimates of when a person is old or an old driver were differentially related with the criteria. The closer the chronological age and subjective age estimates were the lower was the agreement with negative stereotypes and measures to regulate road safety. Findings underline in general that road safety enhancing efforts should avoid highlighting chronological age as the sole driving risk factor to circumvent negative stereotyping with ageing and unjustified driving cessation.

We echo viewpoints presented in recent publications from EcoHealth and other journals arguing for the need to understand linkages between human health, disease ecology, and landscape change. We underscore the importance of incorporating spatialities of human behaviors and perceptions in such analyses to further understandings of socio-ecological interactions mediating human health. We use Buruli ulcer, an emerging necrotizing skin infection and serious health concern in central Ghana, to illustrate our argument.

Emotions towards a relationship partner provide relevant and specific information about relationship quality. Based on this assumption the present study was performed to identify different types of emotional relationship quality of middle-aged adult children with their ageing parents. This was done by cluster analytic procedures in a sample of 1,208 middle-aged adult children (482 men, 726 women). Using ratings of positive and negative emotions towards their mother and father as grouping variables, the same four-cluster solution emerged for both the child-mother relationship and the child-father relationship. Clusters were labelled as amicable, disharmonious, detached and ambivalent relationships. Results showed that especially amicable relationships clearly prevailed followed by ambivalent, detached and disharmonious relationships. Clusters differed significantly with respect to gender of adult child, willingness to support, expected parental support and overt conflicts. In a cross-classification of cluster membership regarding the child-mother relationship (four clusters) and the child-father relationship (four clusters), all possible 16 combinations were observed, with a considerable degree of divergence regarding the type of relationship quality within the same family. Results are discussed with respect to types of emotional relationship quality, within family differences and the intrafamilial regulation of relationship quality.

Cognitive adaptation in the elderly and the motivated use of temporal and social comparisons set the conceptual frame for the present study. Three research questions were investigated in a sample of 2.129 persons aged between 50 and 90 years. First, the direction of social and temporal comparisons for three domains (physical fitness, mental fitness, psychological resilience) was studied, and findings did show that especially lateral followed by upward comparisons were most frequent under both perspectives; downward comparisons clearly showed the least frequency. Second, the distribution of comparison directions was investigated across four age groups. These analyses showed that upward comparisons increased and lateral comparisons decreased across age groups; differential results were observed for the domains under consideration. Third, the relation between social and temporal comparisons and self-esteem was studied. Results obtained here indicated a motivated use of specific comparison directions since downward social comparisons and upward temporal comparisons were most frequent in persons with low self-esteem. Taken together, the study underlines the different functions of social and temporal comparisons in adulthood and old age; it indicates a predominant need for consensus and consistency, and it highlights the importance of self-esteem in cognitive adaptation.

Iron regulatory protein 2 (IRP2)-deficient mice have been reported to suffer from late-onset neurodegeneration by an unknown mechanism. We report that young adult Irp2-/- mice display signs of iron mismanagement within the central iron recycling pathway in the mammalian body, the liver-bone marrow-spleen axis, with altered body iron distribution and compromised hematopoiesis. In comparison with wild-type littermates, Irp2-/- mice are mildly microcytic with reduced serum hemoglobin levels and hematocrit. Serum iron and transferrin saturation are unchanged, and hence microcytosis is not due to an overt decrease in systemic iron availability. The liver and duodenum are iron loaded, while the spleen is iron deficient, associated with a reduced expression of the iron exporter ferroportin. A reduction in transferrin receptor 1 (TfR1) mRNA levels in the bone marrow of Irp2-/- mice can plausibly explain the microcytosis by an intrinsic defect in erythropoiesis due to a failure to adequately protect TfR1 mRNA against degradation. This study links a classic regulator of cellular iron metabolism to systemic iron homeostasis and erythropoietic TfR1 expression. Furthermore, this work uncovers aspects of mammalian iron metabolism that can or cannot be compensated for by the expression of IRP1.

The European Study on Adult Well-being (ESAW), funded by the European Union, was conducted during 2002 and 2003 in Austria, Italy, Luxembourg, The Netherlands, United Kingdom and Sweden. The aim of the interdisciplinary study was the conceptual clarification and the identification of factors contributing to life satisfaction for older people. Five key components were included in the study: (1) physical health and functional status; (2) self-resources; (3) material security; (4) social support resources; and (5) life activity. A representative population of adults aged 50-90 years living independently (not institutionalised) was selected in each participating country, and the actual sample size came very close to the target of 2,000, ranging from 1,854 to 2,417. The total European sample comprised 12,478 respondents. In this paper, mean differences in general and domain-specific life satisfaction between the six countries including age groups and gender are reported and discussed with respect to contextual national characteristics. In general the findings showed a high level in all chosen indicators of life satisfaction across the six countries. National differences depended on the domain under consideration, but the results showed in general that The Netherlands, United Kingdom, Luxembourg and Austria had higher values of life satisfaction compared to Sweden and Italy.

We report the targeted mutagenesis of the murine iron regulatory protein (IRP)-1 and IRP2 genes, respectively, with a classical gene trap construct. Insertion of the targeting cassette into the second intron of either gene by homologous recombination interrupts their open reading frames near the N termini. Mice that are homozygous for the correctly modified IRP1 or IRP2 alleles, respectively, display a strong reduction (90%, IRP1(-/-)) or nondetectable levels (IRP2(-/-)) of the targeted proteins. Interestingly, the pre-mRNAs transcribed from the identical targeting cassettes are processed differently within the two different contexts. Detailed analysis of the respective products identifies the choice of alternative splice and 3' end processing sites in the same tissues in vivo. We discuss the implications for the understanding of RNA processing and for targeting strategies for functional genomics in the mouse.

Generally, plasma membrane (PM) proteins are cotranslationally inserted into the endoplasmic reticulum (ER) and travel in vesicles via the Golgi apparatus to the PM. In the yeast Saccharomyces cerevisiae, the polytopic membrane protein Ist2p is encoded by an mRNA that is localized to the cortex of daughter cells. It has been suggested that IST2 mRNA localization leads to the accumulation of the protein at the PM of daughter cells. Since small- and medium-sized daughter cells only contain cortical, but not perinuclear ER, this implies the local translation of Ist2p specifically at the cortical ER. Here, we show that localization of constitutively expressed IST2 mRNA is required for delivery of Ist2p to the PM of daughter, but not mother cells and that it does not result in daughter-specific Ist2p accumulation. In contrast to a PM-located hexose transporter (Hxt1p) that follows the standard secretory pathway, the trafficking of Ist2p is independent of myosin-mediated vesicular transport. Furthermore, colocalization experiments in mutants of the secretory pathway demonstrate that trafficking of Ist2p does not require the classical secretory machinery. These data suggest the existence of a novel trafficking pathway connecting specialized domains of the ER with the PM.

Class V myosins are motor proteins with functions in vesicle transport, organelle segregation, and RNA localization. Although they have been extensively studied, only little is known about the regulation of their spatial distribution. Here we demonstrate that a GFP fusion protein of the budding yeast class V myosin Myo4p accumulates at the bud cortex and is a component of highly dynamic cortical particles. Bud-specific enrichment depends on Myo4p's association with its cargo, a ribonucleoprotein complex containing the RNA-binding protein She2p. Cortical accumulation of Myo4p at the bud tip can be explained by a transient retention mechanism that requires SHE2 and, apparently, localized mRNAs bound to She2p. A mutant She2 protein that is unable to recognize its cognate target mRNA, ASH1, fails to localize Myo4p. Mutant She2p accumulates inside the nucleus, indicating that She2p shuttles between the nucleus and cytoplasm and is exported in an RNA-dependent manner. Consistently, inhibition of nuclear mRNA export results in nuclear accumulation of She2p and cytoplasmic Myo4p mislocalization. Loss of She2p can be complemented by direct targeting of a heterologous lacZ mRNA to a complex of Myo4p and its associated adaptor She3p, suggesting that She2p's function in Myo4p targeting is to link an mRNA to the motor complex.

RNA localization is a widespread mechanism to achieve localized protein synthesis. In budding yeast, localization of ASH1 mRNA controls daughter cell-specific accumulation of the transcriptional regulator Ash1p, which determines mating type switching. ASH1 mRNA localization depends on four independently acting sequences ('zipcodes') within the mRNA. In addition, the class V myosin Myo4p and a set of She proteins with as yet unknown function are essential for ASH1 localization. Here we show that She2p is a novel RNA-binding protein that binds specifically to ASH1 mRNA in vivo and to ASH1 RNA zip codes in vitro. She2p can interact with She3 protein via She3p's C-terminus and becomes localized to the daughter cell tip upon ASH1 expression. The N-terminal coiled-coil domain of She3p is required to form an RNA-independent complex with the heavy chain of the myosin motor protein Myo4p. She2p and She3p are the first examples of adapters for tethering a localized mRNA to the motor protein and might serve as prototypes for RNA-motor protein adapters.