Continuous symmetry of C60 fullerene and its derivatives

Conventionally, the Ih symmetry of fullerene C60 is accepted which is supported by numerous calculations. However, this conclusion results from the consideration of the molecule electron system, of its odd electrons in particular, in a close-shell approximation without taking the electron spin into account. Passing to the open-shell approximation has lead to both the energy and the symmetry lowering up to Ci. Seemingly contradicting to a high-symmetry pattern of experimental recording, particularly concerning the molecule electronic spectra, the finding is considered in the current paper from the continuous symmetry viewpoint. Exploiting both continuous symmetry measure and continuous symmetry content, was shown that formal Ci symmetry of the molecule is by 99.99% Ih. A similar continuous symmetry analysis of the fullerene monoderivatives gives a reasonable explanation of a large variety of their optical spectra patterns within the framework of the same C1 formal symmetry exhibiting a strong stability of the C60 skeleton.Comment: 11 pages. 5 figures. 6 table

Now or never: perceptions of uniqueness induce acceptance of price increases for experiences more than for objects

Seven studies test and support the prediction that consumers are more willing to accept a price increase for an experiential versus a material purchase; an effect explained by the greater uniqueness of experiences. Critically, the uniqueness model advanced here is found to be independent of the happiness consumers derive from the purchase. To gain a deeper understanding of the uniqueness mechanism, this investigation then advances and tests a four-facet framework of uniqueness (unique opportunity, unique purchase, unique identity, and counterconformity). Together, the findings converge on the conclusion that consumers perceive the opportunity to have a particular experience (vs. object) as more unique, and this unique opportunity increases their willingness to accept a price increase. Overall, this work extends the experiential versus material purchases literature into a new domain—that of pricing; identifies the dimension—uniqueness—and its precise facet responsible for the effect—unique opportunity; and demonstrates that this model unfolds in a pattern distinct from the oft researched model centered on consumer happiness. Theoretical and practical implications are discussed.info:eu-repo/semantics/acceptedVersio

Human Population Differentiation Is Strongly Correlated with Local Recombination Rate

Allele frequency differences across populations can provide valuable information both for studying population structure and for identifying loci that have been targets of natural selection. Here, we examine the relationship between recombination rate and population differentiation in humans by analyzing two uniformly-ascertained, whole-genome data sets. We find that population differentiation as assessed by inter-continental FST shows negative correlation with recombination rate, with FST reduced by 10% in the tenth of the genome with the highest recombination rate compared with the tenth of the genome with the lowest recombination rate (P≪10−12). This pattern cannot be explained by the mutagenic properties of recombination and instead must reflect the impact of selection in the last 100,000 years since human continental populations split. The correlation between recombination rate and FST has a qualitatively different relationship for FST between African and non-African populations and for FST between European and East Asian populations, suggesting varying levels or types of selection in different epochs of human history

Empirical Distributions of F-ST from Large-Scale Human Polymorphism Data

Studies of the apportionment of human genetic variation have long established that most human variation is within population groups and that the additional variation between population groups is small but greatest when comparing different continental populations. These studies often used Wright’s FST that apportions the standardized variance in allele frequencies within and between population groups. Because local adaptations increase population differentiation, high-FST may be found at closely linked loci under selection and used to identify genes undergoing directional or heterotic selection. We re-examined these processes using HapMap data. We analyzed 3 million SNPs on 602 samples from eight worldwide populations and a consensus subset of 1 million SNPs found in all populations. We identified four major features of the data: First, a hierarchically FST analysis showed that only a paucity (12%) of the total genetic variation is distributed between continental populations and even a lesser genetic variation (1%) is found between intra-continental populations. Second, the global FST distribution closely follows an exponential distribution. Third, although the overall FST distribution is similarly shaped (inverse J), FST distributions varies markedly by allele frequency when divided into non-overlapping groups by allele frequency range. Because the mean allele frequency is a crude indicator of allele age, these distributions mark the time-dependent change in genetic differentiation. Finally, the change in mean-FST of these groups is linear in allele frequency. These results suggest that investigating the extremes of the FST distribution for each allele frequency group is more efficient for detecting selection. Consequently, we demonstrate that such extreme SNPs are more clustered along the chromosomes than expected from linkage disequilibrium for each allele frequency group. These genomic regions are therefore likely candidates for natural selection

Multiethnic Genetic Association Studies Improve Power for Locus Discovery

To date, genome-wide association studies have focused almost exclusively on populations of European ancestry. These studies continue with the advent of next-generation sequencing, designed to systematically catalog and test low-frequency variation for a role in disease. A complementary approach would be to focus further efforts on cohorts of multiple ethnicities. This leverages the idea that population genetic drift may have elevated some variants to higher allele frequency in different populations, boosting statistical power to detect an association. Based on empirical allele frequency distributions from eleven populations represented in HapMap Phase 3 and the 1000 Genomes Project, we simulate a range of genetic models to quantify the power of association studies in multiple ethnicities relative to studies that exclusively focus on samples of European ancestry. In each of these simulations, a first phase of GWAS in exclusively European samples is followed by a second GWAS phase in any of the other populations (including a multiethnic design). We find that nontrivial power gains can be achieved by conducting future whole-genome studies in worldwide populations, where, in particular, African populations contribute the largest relative power gains for low-frequency alleles (<5%) of moderate effect that suffer from low power in samples of European descent. Our results emphasize the importance of broadening genetic studies to worldwide populations to ensure efficient discovery of genetic loci contributing to phenotypic trait variability, especially for those traits for which large numbers of samples of European ancestry have already been collected and tested

Genomic Runs of Homozygosity Record Population History and Consanguinity

The human genome is characterised by many runs of homozygous genotypes, where identical haplotypes were inherited from each parent. The length of each run is determined partly by the number of generations since the common ancestor: offspring of cousin marriages have long runs of homozygosity (ROH), while the numerous shorter tracts relate to shared ancestry tens and hundreds of generations ago. Human populations have experienced a wide range of demographic histories and hold diverse cultural attitudes to consanguinity. In a global population dataset, genome-wide analysis of long and shorter ROH allows categorisation of the mainly indigenous populations sampled here into four major groups in which the majority of the population are inferred to have: (a) recent parental relatedness (south and west Asians); (b) shared parental ancestry arising hundreds to thousands of years ago through long term isolation and restricted effective population size (N(e)), but little recent inbreeding (Oceanians); (c) both ancient and recent parental relatedness (Native Americans); and (d) only the background level of shared ancestry relating to continental N(e) (predominantly urban Europeans and East Asians; lowest of all in sub-Saharan African agriculturalists), and the occasional cryptically inbred individual. Moreover, individuals can be positioned along axes representing this demographic historic space. Long runs of homozygosity are therefore a globally widespread and under-appreciated characteristic of our genomes, which record past consanguinity and population isolation and provide a distinctive record of the demographic history of an individual's ancestors. Individual ROH measures will also allow quantification of the disease risk arising from polygenic recessive effects

The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma

We are grateful to Paulo Vieira, Cecília Leão, Manuel T. Silva, Nuno Sousa, Jorge Correia- Pinto, Joana Palha, Margarida Correia-Neves, Margarida Lima and Matthew Berry for all their input throughout these studies and critical reading of the manuscript. We are grateful to the patients who joint this study as well as to all members of the Life and Health Sciences Research Institute and School of Health Sciences, University of Minho, who contributed in any way to the development of this workNon-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.AC, NSO, MTC, and AJA were financially supported by a fellowship from Fundação para a Ciência e Tecnologia, Portugal. MS is a Ciência 2007 fellow. This study was supported by Fundação para a Ciência e Tecnologia, Portugal (PIC/IC/83313/2007) and by Fundação Calouste Gulbenkian, Serviço de Saúde e Desenvolvimento Humano, Portugal (Grant Number:Proc/60666-MM/734). CFS, PB and LC were supported by National Institutes of Health (NIH) grants CA122663 and CA104682, and PB also by NIH grants CA45614 and CA89745

Evolutionary Dynamics of Co-Segregating Gene Clusters Associated with Complex Diseases

BACKGROUND: The distribution of human disease-associated mutations is not random across the human genome. Despite the fact that natural selection continually removes disease-associated mutations, an enrichment of these variants can be observed in regions of low recombination. There are a number of mechanisms by which such a clustering could occur, including genetic perturbations or demographic effects within different populations. Recent genome-wide association studies (GWAS) suggest that single nucleotide polymorphisms (SNPs) associated with complex disease traits are not randomly distributed throughout the genome, but tend to cluster in regions of low recombination. PRINCIPAL FINDINGS: Here we investigated whether deleterious mutations have accumulated in regions of low recombination due to the impact of recent positive selection and genetic hitchhiking. Using publicly available data on common complex diseases and population demography, we observed an enrichment of hitchhiked disease associations in conserved gene clusters subject to selection pressure. Evolutionary analysis revealed that these conserved gene clusters arose by multiple concerted rearrangements events across the vertebrate lineage. We observed distinct clustering of disease-associated SNPs in evolutionary rearranged regions of low recombination and high gene density, which harbor genes involved in immunity, that is, the interleukin cluster on 5q31 or RhoA on 3p21. CONCLUSIONS: Our results suggest that multiple lineage specific rearrangements led to a physical clustering of functionally related and linked genes exhibiting an enrichment of susceptibility loci for complex traits. This implies that besides recent evolutionary adaptations other evolutionary dynamics have played a role in the formation of linked gene clusters associated with complex disease traits

A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway

Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO) cells to ER stress is reverted by stimulation in combination with mild serum withdrawal. Cell death under these conditions was characterized by the appearance of classical apoptosis markers, caspase-9 activation, release of cytochrome c, and was inhibited by knocking down caspase-9, but insensitive to BCL-XL overexpression. Similarly, the resistance of BIM and PUMA double deficient cells to ER stress was reverted by mild serum withdrawal. Surprisingly, BAX/BAK-independent cell death did not require Cyclophilin D (CypD) expression, an important regulator of the mitochondrial permeability transition pore. Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria