PANDIT: an evolution-centric database of protein and associated nucleotide domains with inferred trees

PANDIT is a database of homologous sequence alignments accompanied by estimates of their corresponding phylogenetic trees. It provides a valuable resource to those studying phylogenetic methodology and the evolution of coding-DNA and protein sequences. Currently in version 17.0, PANDIT comprises 7738 families of homologous protein domains; for each family, DNA and corresponding amino acid sequence multiple alignments are available together with high quality phylogenetic tree estimates. Recent improvements include expanded methods for phylogenetic tree inference, assessment of alignment quality and a redesigned web interface, available at the URL

Towards a Molecular Systems Model of Coronary Artery Disease

Peer reviewe

IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy

BACKGROUND: Genetic studies have demonstrated a strong association between single nucleotide polymorphisms (SNPs) at IL28B and response to treatment with peginterferon (PEG) and ribavirin (RBV) in HCV monoinfected persons. We sought to test these associations in a prospective PEG / weight based ribavirin (WBR) treatment trial (ACTG A5178) (National Institution of Health registration number NCT00078403) in persons with HCV-HIV coinfection, and to develop a prediction score. METHODS: We selected subjects enrolled in A5178 who completed at least the first 12 weeks of the trial and had DNA available, and genotyped three SNPs at IL28B (rs12979860, rs12980275, rs8099917). We used multivariate logistic regression analysis to evaluate the association between IL28B SNPs and HCV treatment outcomes and to develop the prediction score. RESULTS: 231 HCV/HIV coinfected subjects were included. We observed a strong association between IL28B genotype and response to therapy among those with genotypes 1 or 4 (odds ratio for complete early virologic responses (cEVR) and sustained virologic response (SVR) was 2.98 [1.7-5.3] and 3.4 [1.7-6.9], respectively, for each additional copy of the C allele of rs12979860). Differences in frequency of the responder allele explained some of the discrepancy in HCV treatment outcomes between blacks and whites. A simple pretreatment prediction score that incorporates the IL28B genotype and baseline HCV viral load has a 93% negative predictive value (NPV) for SVR. CONCLUSIONS: IL28B SNPs have an additive allele dose effect in predicting HCV treatment outcomes in HCV/HIV coinfected persons and can be incorporated into a simple pretreatment prediction score that could minimize the risk of exposure to PEG/RBV therapy for persons with unfavorable scores

Довідкові регіональні видання з геральдики

Одним з джерел інформації про наявність історичних гербів міст України та новотворів 60-х–80-х рр. ХХ ст. виступає «Алфавитный каталог городов, поселков, сел, губерний и областей России, СНГ, бывших союзных республик СССР, имеющих старые и современные гербы». Автор рецензії проаналізував принципи укладання подібних джерел інформації, зробив свої зауваження та висловив побажання щодо їх вдосконалення.«Alphabetical catalogue of towns, settlements, villages, provinces and regions of Russia, Commonwealth of Independent States, former Soviet Republics of the USSR, which have old and present-day coat of arms» is one of the sources that gives information about historical coat of arms and newly formed emblems of Ukraine during 60th – 80th of XX century. The author of the review analysed the structure of similar sources and made her remarks and suggestion regarding to its improvement

Rs964184 (APOA5-A4-C3-A1) Is Related to Elevated Plasma Triglyceride Levels, but Not to an Increased Risk for Vascular Events in Patients with Clinically Manifest Vascular Disease

Background: Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Methods: Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. Results: The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10−19), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01–0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09–0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides 27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86–1.13). Conclusion: The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients

Common Variants in 40 Genes Assessed for Diabetes Incidence and Response to Metformin and Lifestyle Intervention in the Diabetes Prevention Program

OBJECTIVE: Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions. RESEARCH DESIGN AND METHODS: We selected SNPs identified by prior genome-wide association studies for type 2 diabetes and related traits, or capturing common variation in 40 candidate genes previously associated with type 2 diabetes, implicated in monogenic diabetes, encoding type 2 diabetes drug targets or drug-metabolizing/transporting enzymes, or involved in relevant physiological processes. We analyzed 1,590 SNPs for association with incident diabetes and their interaction with response to metformin or lifestyle interventions in 2,994 DPP participants. We controlled for multiple hypothesis testing by assessing false discovery rates. RESULTS: We replicated the association of variants in the metformin transporter gene $SLC47A1$ with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene $STK11$, the AMPK subunit genes $PRKAA1$ and $PRKAA2$, and a missense SNP in $SLC22A1$, which encodes another metformin transporter. The most significant association with diabetes incidence occurred in the AMPK subunit gene $PRKAG2$ (hazard ratio 1.24, 95% CI 1.09–1.40, P = 7 × 10$^{−4}$). Overall, there were nominal associations with diabetes incidence at 85 SNPs and nominal interactions with the metformin and lifestyle interventions at 91 and 69 mostly nonoverlapping SNPs, respectively. The lowest $P$ values were consistent with experiment-wide 33% false discovery rates. CONCLUSIONS: We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples

Common Variants in 40 Genes Assessed for Diabetes Incidence and Response to Metformin and Lifestyle Intervention in the Diabetes Prevention Program

OBJECTIVE: Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions. RESEARCH DESIGN AND METHODS: We selected SNPs identified by prior genome-wide association studies for type 2 diabetes and related traits, or capturing common variation in 40 candidate genes previously associated with type 2 diabetes, implicated in monogenic diabetes, encoding type 2 diabetes drug targets or drug-metabolizing/transporting enzymes, or involved in relevant physiological processes. We analyzed 1,590 SNPs for association with incident diabetes and their interaction with response to metformin or lifestyle interventions in 2,994 DPP participants. We controlled for multiple hypothesis testing by assessing false discovery rates. RESULTS: We replicated the association of variants in the metformin transporter gene SLC47A1 with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1 and PRKAA2, and a missense SNP in SLC22A1, which encodes another metformin transporter. The most significant association with diabetes incidence occurred in the AMPK subunit gene PRKAG2 (hazard ratio 1.24, 95% CI 1.09-1.40, P = 7 × 10(-4)). Overall, there were nominal associations with diabetes incidence at 85 SNPs and nominal interactions with the metformin and lifestyle interventions at 91 and 69 mostly nonoverlapping SNPs, respectively. The lowest P values were consistent with experiment-wide 33% false discovery rates. CONCLUSIONS: We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples

Метафорична картина світу та її місце у системі світів

Статья посвящается исследованию понятия метафорической картины мира, целесообразность выделения которой автор объясняет тем, что по аналогии с языковой и концептуальной картинами мира, термин "метафорическая картина мира" содержит информацию о сложной структуре многосмысловых значений, которые в силу своей метафорической природе гармонически объединяются.У статті йдеться про поняття метафоричної картини світу, доцільність виділення якої авторка пояснює тим, що за аналогією до мовної й концептуальної картин світу, термін "метафорична картина світу" вміщує інформацію про складну структуру багатосмислових значень, що завдяки своїй метафоричній природі гармонійно поєднуються.The article deals with the notion of metaphorical world picture connected with the general principle of conceptualization. The term "metaphorical world picture" consists of a complex structure of various meanings harmonically combined due to their metaphorical nature