Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.</p

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Genome-wide association study identifies 74 loci associated with educational attainment

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases

House Housing: An Untimely History of Architecture and Real Estate in Nineteen Episodes: Una storia inattuale dell’architettura e dei beni immobiliari in diciannove episodi

0info:eu-repo/semantics/published

An ellipsometric study of interaction of anti-cancer agent erufosine on lipid model systems

The study of the interaction of native and model lipid membranes with pharmacological agents is a subject of outstanding interest in the research of biomaterials, biosensors, the production of devices using organic layers. In last few years, the study of biomimetic membrane systems in the form of vesicles, lipid monolayers and solid-supported lipid layers has attracted a significant attention among researchers. In this work, we present a capability of the spectroscopic ellipsometry as a novel technique to study solid - supported lipid model systems and decode the effect of the anti-cancer agent erufosine on lipids. Importantly, this technique has been proved as a fast and non-invasive method. The lipid films are composed of phosphatidylcholine, sphingomyelin and cholesterol in different concentrations and we have employed a thin gold film for supporting their surface. Erufosine (EPC3) is known as membrane-acting anti-tumor agent and in this respect has been investigated its effect on the model systems. The obtained results have revealed reorganization of lipid layers at different extent by interaction with the anti-cancer agent.Acknowledge the financial support of EC ERASMUS MUNDUS: NANOPHI and FNI, DN 11/1/2017 projects

Micellar curcumin improves the antibacterial activity of the alkylphosphocholines erufosine and miltefosine against pathogenic Staphyloccocus aureus strains

In the light of the emerging bacterial resistance to broad-spectrum antibiotics, the search for new antibacterial therapeutics and drug combinations is one of the most challenging topics nowadays. In the present study, we investigated for the first time the antibacterial and biofilm inhibitory effects of the third generation anticancer alkylphosphocholine (APC) erufosine against pathogenic Staphylococcus aureus strains in comparison to the prototype of this pharmacological class of drugs, miltefosine. We also searched for synergistic antibacterial combinations between both APCs and curcumin incorporated in copolymeric micelles based on Pluronic® P123 or a mixture of Pluronic® P123 and Pluronic® F127 (P123/F127). The obtained quantitative redox-activity experimental data and drug–drug interactions were evaluated by using mathematical models in the MAPLE software. Similar to miltefosine, erufosine showed a moderate bacteriostatic effect in clinically relevant concentrations (50 ÷ 60 µmol/L) and inhibited the redox activity of the treated bacteria up to 90% at minimal inhibitory concentrations. The effect of both APCs towards methicillin resistant staphylococci was enhanced by combinations with P123/F127 micellar CRM at a ratio of 1:1. Erufosine showed a stronger median biofilm inhibition at lower concentrations (MBIC50 = 1.87 µmol/L) than miltefosine (MBIC50 = 6.0 µmol/L) and curcumin (MBIC50 = 24.84 µmol/L) as demonstrated by quantification of biofilm-bound bacteria. In conclusion, the estimated antibacterial activity of erufosine widens the spectrum of its useful pharmacological effects, which is important for its clinical development. The established synergistic and additive drug combinations could be beneficial for the application of both APCs in cancer therapy, since numerous malignancies are accompanied by bacterial infections

Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes. Part I. Synthesis

The prepn. of stereoisomeric 1,2-bis(3-hydroxyphenyl)ethylenediamines (L) from meso-1,2-bis(2-hydroxyphenyl)ethylenediamine and 3-methoxybenzaldehyde by a diaza-Cope-rearrangement and subsequent ether cleavage with BBr3 and their conversion to PtLCl2 with K2PtCl4 are described. PtLCl2 were characterized by CD, IR and NMR spectra