Hopelessly Mortal: The Role of Mortality Salience, Immortality and Trait Self-esteem in Personal Hope

Do people lose hope when thinking about death? Based on Terror Management Theory, we predicted that thoughts of death (i.e., mortality salience) would reduce personal hope for people low, but not high, in self-esteem, and that this reduction in hope would be ameliorated by promises of immortality. In Studies 1 and 2, mortality salience reduced personal hope for people low in self-esteem, but not for people high in self-esteem. In Study 3, mortality salience reduced hope for people low in self-esteem when they read an argument that there is no afterlife, but not when they read “evidence” supporting life after death. In Study 4, this effect was replicated with an essay affirming scientific medical advances that promise immortality. Together, these findings uniquely demonstrate that thoughts of mortality interact with trait self-esteem to cause changes in personal hope, and that literal immortality beliefs can aid psychological adjustment when thinking about death. Implications for understanding personal hope, trait self-esteem, afterlife beliefs and terror management are discussed

QTL analysis of resistance to Fusarium head blight in Swiss winter wheat ( Triticum aestivum L.)

Fusarium head blight (FHB) of wheat is a widespread and destructive disease which occurs in humid and semi-humid areas. FHB epidemics can cause serious yield and quality losses under favorable climatic conditions, but the major concern is the contamination of grains with mycotoxins. Resistance to FHB is quantitatively inherited and greatly influenced by the environment. Its evaluation is costly and time-consuming. The genetic basis of FHB resistance has mainly been studied in spring wheat. The objective of this study was to map quantitative trait loci (QTLs) for resistance to FHB in a population of 240 recombinant inbred lines (RILs) derived from a cross between the two Swiss winter wheat cultivars Arina (resistant) and Forno (susceptible). The RILs were genotyped with microsatellite and RFLP markers. The resulting genetic map comprises 380 loci and spans 3,086cM. The 240 RILs were evaluated for resistance to FHB in six field trials over 3 years. Composite interval mapping (CIM) analyses carried out on FHB AUDPC (i.e. mean values across six environments) revealed eight QTLs which altogether explained 47% of the phenotypic variance. The three main QTLs were mapped on the long arms of chromosomes 6D (R 2=22%), 5B (R 2=14%) and 4A (R 2=10%). The QTL detected on 5B originated from the susceptible parent Forno. Other QTLs with smaller effects on FHB resistance were detected on chromosomes 2AL, 3AL, 3BL, 3DS and 5A

Detection of QTLs for Stagonospora glume blotch resistance in Swiss winter wheat

Stagonospora nodorum is the causal agent of the Stagonospora glume blotch disease in hexaploid wheat. The Swiss winter bread wheat cv. 'Arina' has a highly effective, durable and quantitative glume blotch resistance. We studied 240 single seed descent (SSD)-derived lines of an 'Arina × Forno' F5:7 population to identify and map quantitative trait loci (QTLs) for glume blotch resistance under natural infestation. Using composite interval mapping (CIM) and LOD>4.5, we detected two chromosomal regions on chromosome arms 3BS and 4BL which were specifically associated with glume blotch resistance. These identified QTLs were designated QSng.sfr-3BS and QSng.sfr-4BL, respectively. QSng.sfr-3BS peaked at the locus Xgwm389 in the telomeric region of the short arm of chromosome 3B and explained 31.2% of the observed phenotypic variance for the resistance within the population. The responsible QSng.sfr-3BS allele originated from the resistant parent 'Arina'. The QTL QSng.sfr-4BL (19.1%) mapped to chromosome arm 4BL ('Forno' allele) very close to two known genes, TaMlo and a catalase (Cat). Both QTL alleles combined could enhance the resistance level by about 50%. Additionally, they showed significant epistatic effects (4.4%). We found PCR-based microsatellite markers closely linked to QSng.sfr-3BS (gwm389) and QSng.sfr-4BL (gwm251) which make marker-assisted selection (MAS) for Stagonospora glume blotch resistance feasible. We also found one resistance QTL, QSng.sfr-5BL, on the long arm of chromosome 5B which overlapped with QTLs for plant height as well as heading tim

Dissection of quantitative and durable leaf rust resistance in Swiss winter wheat reveals a major resistance QTL in the Lr34 chromosomal region

The Swiss winter bread wheat cv. ‘Forno' has a highly effective, durable and quantitative leaf rust (Puccinia triticina Eriks.) resistance which is associated with leaf tip necrosis (LTN). We studied 240 single seed descent lines of an ‘Arina×Forno' F5:7 population to identify and map quantitative trait loci (QTLs) for leaf rust resistance and LTN. Percentage of infected leaf area (%) and the response to infection (RI) were evaluated in seven field trials and were transformed to the area under the disease progress curves (AUDPC). Using composite interval mapping and LOD>4.4, we identified eight chromosomal regions specifically associated with resistance. The largest and most consistent leaf rust resistance locus was identified on the short arm of chromosome 7D (32.6% of variance explained for AUDPC_% and 42.6% for AUDPC_RI) together with the major QTL for LTN (R 2=55.6%) in the same chromosomal region as Lr34 (Xgwm295). A second major leaf rust resistance QTL (R 2=28% and 31.5%, respectively) was located on chromosome arm 1BS close to Xgwm604 and was not associated with LTN. Additional minor QTLs for LTN (2DL, 3DL, 4BS and 5AL) and leaf rust resistance were identified. These latter QTLs might correspond to the leaf rust resistance genes Lr2 or Lr22 (2DS) and Lr14a (7BL

An integrative genetic linkage map of winter wheat ( Triticum aestivum L.)

We constructed a genetic linkage map based on a cross between two Swiss winter wheat (Triticum aestivum L.) varieties, Arina and Forno. Two-hundred and forty F5 single-seed descent (SSD)-derived lines were analysed with 112 restriction fragment length polymorphism (RFLP) anonymous probes, 18 wheat cDNA clones coding for putative stress or defence-related proteins and 179 simple-sequence repeat (SSR) primer-pairs. The 309 markers revealed 396 segregating loci. Linkage analysis defined 27 linkage groups that could all be assigned to chromosomes or chromosome arms. The resulting genetic map comprises 380 loci and spans 3,086cM with 1,131cM for the A genome, 920cM for the B genome and 1,036cM for the D genome. Seventeen percent of the loci showed a significant (P < 0.05) deviation from a 1:1 ratio, most of them in favour of the Arina alleles. This map enabled the mapping of QTLs for resistance against several fungal diseases such as Stagonospora glume blotch, leaf rust and Fusarium head blight. It will also be very useful for wheat genetic mapping, as it combines RFLP and SSR markers that were previously located on separate map

KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.

Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of Plasmodium cynomolgi (an excellent and accessible model for Plasmodium vivax). In this assay, primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially a radical cure

Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.

A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing

Yeast Protein Interactome Topology Provides Framework for Coordinated-Functionality

The architecture of the network of protein-protein physical interactions in Saccharomyces cerevisiae is exposed through the combination of two complementary theoretical network measures, betweenness centrality and `Q-modularity'. The yeast interactome is characterized by well-defined topological modules connected via a small number of inter-module protein interactions. Should such topological inter-module connections turn out to constitute a form of functional coordination between the modules, we speculate that this coordination is occurring typically in a pair-wise fashion, rather than by way of high-degree hub proteins responsible for coordinating multiple modules. The unique non-hub-centric hierarchical organization of the interactome is not reproduced by gene duplication-and-divergence stochastic growth models that disregard global selective pressures.Comment: Final, revised version. 13 pages. Please see Nucleic Acids open access article for higher resolution figure

MCL-CAw: A refinement of MCL for detecting yeast complexes from weighted PPI networks by incorporating core-attachment structure

Abstract Background The reconstruction of protein complexes from the physical interactome of organisms serves as a building block towards understanding the higher level organization of the cell. Over the past few years, several independent high-throughput experiments have helped to catalogue enormous amount of physical protein interaction data from organisms such as yeast. However, these individual datasets show lack of correlation with each other and also contain substantial number of false positives (noise). Over these years, several affinity scoring schemes have also been devised to improve the qualities of these datasets. Therefore, the challenge now is to detect meaningful as well as novel complexes from protein interaction (PPI) networks derived by combining datasets from multiple sources and by making use of these affinity scoring schemes. In the attempt towards tackling this challenge, the Markov Clustering algorithm (MCL) has proved to be a popular and reasonably successful method, mainly due to its scalability, robustness, and ability to work on scored (weighted) networks. However, MCL produces many noisy clusters, which either do not match known complexes or have additional proteins that reduce the accuracies of correctly predicted complexes. Results Inspired by recent experimental observations by Gavin and colleagues on the modularity structure in yeast complexes and the distinctive properties of "core" and "attachment" proteins, we develop a core-attachment based refinement method coupled to MCL for reconstruction of yeast complexes from scored (weighted) PPI networks. We combine physical interactions from two recent "pull-down" experiments to generate an unscored PPI network. We then score this network using available affinity scoring schemes to generate multiple scored PPI networks. The evaluation of our method (called MCL-CAw) on these networks shows that: (i) MCL-CAw derives larger number of yeast complexes and with better accuracies than MCL, particularly in the presence of natural noise; (ii) Affinity scoring can effectively reduce the impact of noise on MCL-CAw and thereby improve the quality (precision and recall) of its predicted complexes; (iii) MCL-CAw responds well to most available scoring schemes. We discuss several instances where MCL-CAw was successful in deriving meaningful complexes, and where it missed a few proteins or whole complexes due to affinity scoring of the networks. We compare MCL-CAw with several recent complex detection algorithms on unscored and scored networks, and assess the relative performance of the algorithms on these networks. Further, we study the impact of augmenting physical datasets with computationally inferred interactions for complex detection. Finally, we analyse the essentiality of proteins within predicted complexes to understand a possible correlation between protein essentiality and their ability to form complexes. Conclusions We demonstrate that core-attachment based refinement in MCL-CAw improves the predictions of MCL on yeast PPI networks. We show that affinity scoring improves the performance of MCL-CAw.http://deepblue.lib.umich.edu/bitstream/2027.42/78256/1/1471-2105-11-504.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/2/1471-2105-11-504-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/3/1471-2105-11-504-S2.ZIPhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/4/1471-2105-11-504.pdfPeer Reviewe