A Gene's Ability to Buffer Variation Is Predicted by Its Fitness Contribution and Genetic Interactions

BACKGROUND: Many single-gene knockouts result in increased phenotypic (e.g., morphological) variability among the mutant's offspring. This has been interpreted as an intrinsic ability of genes to buffer genetic and environmental variation. A phenotypic capacitor is a gene that appears to mask phenotypic variation: when knocked out, the offspring shows more variability than the wild type. Theory predicts that this phenotypic potential should be correlated with a gene's knockout fitness and its number of negative genetic interactions. Based on experimentally measured phenotypic capacity, it was suggested that knockout fitness was unimportant, but that phenotypic capacitors tend to be hubs in genetic and physical interaction networks. METHODOLOGY/PRINCIPAL FINDINGS: We re-analyse the available experimental data in a combined model, which includes knockout fitness and network parameters as well as expression level and protein length as predictors of phenotypic potential. Contrary to previous conclusions, we find that the strongest predictor is in fact haploid knockout fitness (responsible for 9% of the variation in phenotypic potential), with an additional contribution from the genetic interaction network (5%); once these two factors are taken into account, protein-protein interactions do not make any additional contribution to the variation in phenotypic potential. CONCLUSIONS/SIGNIFICANCE: We conclude that phenotypic potential is not a mysterious "emergent" property of cellular networks. Instead, it is very simply determined by the overall fitness reduction of the organism (which in its compromised state can no longer compensate for multiple factors that contribute to phenotypic variation), and by the number (and presumably nature) of genetic interactions of the knocked-out gene. In this light, Hsp90, the prototypical phenotypic capacitor, may not be representative: typical phenotypic capacitors are not direct "buffers" of variation, but are simply genes encoding central cellular functions

Kebab: Kinetochore and EB1 Associated Basic Protein That Dynamically Changes Its Localisation during Drosophila Mitosis

Microtubule plus ends are dynamic ends that interact with other cellular structures. Microtubule plus end tracking proteins are considered to play important roles in the regulation of microtubule plus ends. Recent studies revealed that EB1 is the central regulator for microtubule plus end tracking proteins by recruiting them to microtubule plus ends through direct interaction. Here we report the identification of a novel Drosophila protein, which we call Kebab (kinetochore and EB1 associated basic protein), through in vitro expression screening for EB1-interacting proteins. Kebab fused to GFP shows a novel pattern of dynamic localisation in mitosis. It localises to kinetochores weakly in metaphase and accumulates progressively during anaphase. In telophase, it associates with microtubules in central-spindle and centrosomal regions. The localisation to kinetochores depends on microtubules. The protein has a domain most similar to the atypical CH domain of Ndc80, and a coiled-coil domain. The interaction with EB1 is mediated by two SxIP motifs but is not required for the localisation. Depletion of Kebab in cultured cells by RNA interference did not show obvious defects in mitotic progression or microtubule organisation. Generation of mutants lacking the kebab gene indicated that Kebab is dispensable for viability and fertility

Mental health issues in unaccompanied refugee minors

Previous studies about unaccompanied refugee minors (URMs) showed that they are a highly vulnerable group who have greater psychiatric morbidity than the general population. This review focuses on mental health issues among URMs. Articles in databases PsycINFO, Medline and PubMed from 1998 to 2008 addressing this topic were reviewed. The literature had a considerable emphasis on the assessment of PTSD symptoms. Results revealed higher levels of PTSD symptoms in comparison to the norm populations and accompanied refugee minors. In several studies, age and female gender predicted or influenced PTSD symptoms. The existing literature only permits limited conclusions on this very hard to reach population. Future research should include the analysis of long-term outcomes, stress management and a more thorough analysis of the whole range of psychopathology. Additionally, the development of culturally sensitive norms and standardized measures for diverse ethnic groups is of great importance

Structural Change and the Fall of Income Inequality in Latin America : Agricultural Development, Inter-sectoral Duality, and the Kuznets Curve

In this study we approach the recent decline in income inequality in Latin America from the perspective of structural change with a focus on the relative performance of the agricultural sector. Our focus is on the underlying forces implied by Kuznets (1965). We zoom in on the relative performance of agriculture in the development process and the rural-urban duality and pay particular attention to the last couple of decades in relation to the entire post-1950 period. We attempt to estimate empirically possible theoretical relations with regard to these patterns by posing the following basic questions: how does the resurgence of agriculture relate to the reduction of income inequality and to what extent is this an expression of Latin America moving downward on the Kuznets curve? The literature on agriculture’s relation to the recent changes of income distribution in Latin America is quite limited. For instance, in a recent ECLAC report titled “Structural change for equality” (2012), the role of agriculture is not even mentioned. By agriculture we mean both farming and agro-business that processes and transports that output. To our knowledge, this paper is the first attempt to investigate this relationship for the recent decades in the perspective of structural change in Latin America. There are strong theoretical reasons to connect agricultural development to income distribution. The closing of the rural-urban income gap reflects what Reynolds (1975) called a “dynamic” transformation of agriculture and relates to the contribution agriculture provides for overall growth of the economy. In addition, the elasticity of poverty reduction with respect to growth is estimated to be stronger when growth emanates in the agricultural sector (Ravallion and Chen 2007, de Janvry and Sadoulet 2009). Productivity growth in the lagging sector should also contribute to sectoral labor productivity to convergence and thus helps to reduce inequality (Timmer 1988). For these reasons, the resurgence of agriculture driven partly by improving commodity prices should be given due attention when assessing the decline in income inequality in Latin America. According to the logic of the Kuznets curve, the hypothesized “turning point” of the inverted U-curve is generated by a reduction of income inequality in one or both of the sectors and/or a reduction of the rural-urban income gap as the weight of the agricultural sector diminishes, and the income per capita gap between them declines. We find that the recent decline in income inequality is related to the recent resurgence of Latin American agriculture, and, by inference, its lack of decline across most of the 20th century must be related to a lack of productivity change in agriculture. We provide estimates showing that during the recent decades inter-sectoral duality has been reduced by agricultural productivity growth. The duality expressed as an inter-sectoral Gini shows the shape of an inverted U-curve and as such the closing of the rural-urban income gap corroborates with the theoretical expectations postulated by Kuznets. The wider implication of the study is, however, that with slower growth in agricultural labor productivity, continuing improvement in the income distribution becomes more difficult. In the absence of strong manufacturing growth, agriculture might be able to reduce income inequality further if agro-industries remain unskilled labor intensive, thus raising the opportunity cost of unskilled workers. On the other hand, the traditional service sector has perhaps become the “new agricultural sector” in terms of productivity and labor surplus. In other words, the source of the remaining dualism does not come only from rural areas, but also from urban areas

War and Bereavement: Consequences for Mental and Physical Distress

Background: Little is known about the long-term impact of the killing of a parent in childhood or adolescence during war on distress and disability in young adulthood. This study assessed current prevalence rates of mental disorders and levels of dysfunction among young adults who had lost their father due to war-related violence in childhood or adolescence. Methods: 179 bereaved young adults and 175 non-bereaved young adults were interviewed a decade after experiencing the war in Kosovo. Prevalence rates of Major Depressive Episode (MDE), anxiety, and substance use disorders, and current suicide risk were assessed using the Mini–International Neuropsychiatric Interview. The syndrome of Prolonged Grief Disorder (PGD) was assessed with the Prolonged Grief Disorder Interview (PG-13). Somatic symptoms were measured with the Patient Health Questionnaire. General health distress was assessed with the General Health Questionnaire. Findings: Bereaved participants were significantly more likely to suffer from either MDE or any anxiety disorder than nonbereaved participants (58.7 % vs. 40%). Among bereaved participants, 39.7 % met criteria for Post-Traumatic Stress Disorder, 34.6 % for PGD, and 22.3 % for MDE. Bereaved participants with PGD were more likely to suffer from MDE, any anxiety disorder, or current suicide risk than bereaved participants without PGD. Furthermore, these participants reported significantly greater physical distress than bereaved participants without PGD. Conclusion: War-related loss during middle childhood and adolescence presents significant risk for adverse mental healt

Regulation of the let-7a-3 Promoter by NF-κB

Changes in microRNA expression have been linked to a wide array of pathological states. However, little is known about the regulation of microRNA expression. The let-7 microRNA is a tumor suppressor that inhibits cellular proliferation and promotes differentiation, and is frequently lost in tumors. We investigated the transcriptional regulation of two let-7 family members, let-7a-3 and let-7b, which form a microRNA cluster and are located 864 bp apart on chromosome 22q13.31. Previous reports present conflicting data on the role of the NF-κB transcription factor in regulating let-7. We cloned three fragments upstream of the let-7a-3/let-7b miRNA genomic region into a plasmid containing a luciferase reporter gene. Ectopic expression of subunits of NF-κB (p50 or p65/RelA) significantly increased luciferase activity in HeLa, 293, 293T and 3T3 cells, indicating that the let-7a-3/let-7b promoter is highly responsive to NF-κB. Mutation of a putative NF-κB binding site at bp −833 reduced basal promoter activity and decreased promoter activity in the presence of p50 or p65 overexpression. Mutation of a second putative binding site, at bp −947 also decreased promoter activity basally and in response to p65 induction, indicating that both sites contribute to NF-κB responsiveness. While the levels of the endogenous primary let-7a and let-7b transcript were induced in response to NF-κB overexpression in 293T cells, the levels of fully processed, mature let-7a and let-7b miRNAs did not increase. Instead, levels of Lin-28B, a protein that blocks let-7 maturation, were induced by NF-κB. Increased Lin-28B levels could contribute to the lack of an increase in mature let-7a and let-7b. Our results suggest that the final biological outcome of NF-κB activation on let-7 expression may vary depending upon the cellular context. We discuss our results in the context of NF-κB activity in repressing self-renewal and promoting differentiation

Civic Participation and Other Interventions That Promote Children\u2019s Tolerance of Migrants

In this chapter, we begin by providing a definition of \u2018tolerance\u2019, illustrating the wide range of attributes associated with the concept in the literature. Second, we identify some key paths through which tolerance can develop at different stages of an individual\u2019s development. Through a literature review, we will track some of the factors that can increase tolerance toward migrants during early and late stages development. Finally, we will conclude by presenting an overview of methodological approaches that practitioners have at their disposal to promote tolerance toward migrants

Better mental health in children of Vietnamese refugees compared with their Norwegian peers - a matter of cultural difference?

<p>Abstract</p> <p>Background</p> <p>There are conflicting results on whether immigrant children are at a heightened risk of mental health problems compared with native youth in the resettlement country.</p> <p>The objective of the study</p> <p>To compare the mental health of 94 Norwegian-born children from a community cohort of Vietnamese refugees, aged 4 - 18 years, with that of a Norwegian community sample.</p> <p>Methods</p> <p>The SDQ was completed by two types of informants; the children's self-reports, and the parents' reports, for comparison with Norwegian data from the Health Profiles for Children and Youth in the Akershus study.</p> <p>Results</p> <p>The self-perceived mental health of second-generation Vietnamese in Norway was better than that of their Norwegian compatriots, as assessed by the SDQ. In the Norwegian-Vietnamese group, both children and parents reported a higher level of functioning.</p> <p>Conclusion</p> <p>This surprising finding may result from the lower prevalence of mental distress in Norwegian-Vietnamese children compared with their Norwegian peers, or from biased reports and cultural differences in reporting emotional and behavioural problems. These findings may represent the positive results of the children's bi-cultural competencies.</p