Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

Ubiquitin Ligases of the N-End Rule Pathway: Assessment of Mutations in UBR1 That Cause the Johanson-Blizzard Syndrome.

Background: Johanson-Blizzard syndrome (JBS; OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, facial dysmorphism with the characteristic nasal wing hypoplasia, multiple malformations, and frequent mental retardation. Our previous work has shown that JBS is caused by mutations in human UBR1, which encodes one of the E3 ubiquitin ligases of the N-end rule pathway. The N-end rule relates the regulation of the in vivo half-life of a protein to the identity of its N-terminal residue. One class of degradation signals (degrons) recognized by UBR1 are destabilizing N-terminal residues of protein substrates.Methodology/Principal Findings: Most JBS-causing alterations of UBR1 are nonsense, frameshift or splice-site mutations that abolish UBR1 activity. We report here missense mutations of human UBR1 in patients with milder variants of JBS. These single-residue changes, including a previously reported missense mutation, involve positions in the RING-H2 and UBR domains of UBR1 that are conserved among eukaryotes. Taking advantage of this conservation, we constructed alleles of the yeast Saccharomyces cerevisiae UBR1 that were counterparts of missense JBS-UBR1 alleles. Among these yeast Ubr1 mutants, one of them (H160R) was inactive in yeast-based activity assays, the other one (Q1224E) had a detectable but weak activity, and the third one (V146L) exhibited a decreased but significant activity, in agreement with manifestations of JBS in the corresponding JBS patients.Conclusions/Significance: These results, made possible by modeling defects of a human ubiquitin ligase in its yeast counterpart, verified and confirmed the relevance of specific missense UBR1 alleles to JBS, and suggested that a residual activity of a missense allele is causally associated with milder variants of JBS.

Using Songs in Primary Education: Advantages and Challenges

Aquesta recerca està basada en l’observació de les cançons per aprendre i ensenyar la llengua anglesa en l’etapa d’Educació Primària. S’analitza la cançó com un recurs eficaç per aprendre aquesta llengua, així com també s’observen els avantatges i desavantatges que es poden trobar en l’ús de les cançons a les aules de Primària. A partir d’una aplicació pràctica també s’estudia la validesa d’aquest recurs en el primer i darrer curs de la Primària. A més a més, es mesura la motivació que mostren els alumnes davant d’aquesta eina d’aprenentatge. Finalment, es presenten els resultats obtinguts en l’aplicació pràctica que s’ha portat a terme en una escola i les conclusions que s’extreuen a partir de la justificació teòrica i els resultats obtinguts a partir de les sessions pràctiques.

Iowa's frog and toad survey, 1995-2003.

This survey began in response to widespread interest of declines in amphibians. More recently, a comprehensive statewide planning group discovered 44% of Iowa’s herpetofauna (amphibians and reptiles) to be of special concern. In response to these concerns, the Iowa Department of Natural Resources Wildlife Diversity Program (WDP) initiated an auditory survey for calling anurans to determine geographic distributions within the state. This survey has established itself as an extensive, long term monitoring program. This 2005 report is the second edition since the first report of this survey was shared in 1998 by then program biologist Lisa Hemesath. The goals of the survey are to: (1) determine the distributions of Iowa’s anuran species, (2) determine population trends for each species, and (3) promote education about aquatic life by using volunteers to conduct the survey. In addition to Iowa, volunteer-based auditory surveys for frogs and toads are currently being used in the Midwest by Wisconsin, Minnesota, Missouri, and Illinois.

Water planning law and government.

Water planning efforts typically identify problems and needs. But simply calling attention to issues is usually not enough to spur action; the end result of many well-intentioned planning efforts is a report that ends up gathering dust on a shelf. Vague recommendations like “Water conservation measures should be implemented” usually accomplish little by themselves as they don’t assign responsibility to anyone. Success is more likely when an implementation strategy — who can and should do what — is developed as part of the planning process. The more detailed and specific the implementation strategy, the greater the chance that something will actually be done. The question then becomes who has the legal authority or responsibility to do what? Are new laws and programs needed or can existing ones be used to implement the recommendations? ... This document is divided into four main parts. The first, “Carrots and Sticks” looks at two basic approaches — regulatory and non-regulatory — that can be, and are, used to carry out water policy. Both have advantages and disadvantages that need to be considered. The second, “The powers of federal, state and local governments…,” looks at the constitutional powers the federal government and state and local governments have to carry out water policy. An initial look at the U. S. Constitution might suggest the federal government’s regulatory authority over water is limited but, in fact, its powers are very substantial. States have considerable authority to do a number of things but have to be mindful of any federal efforts that might conflict with those state efforts. And local governments can only do those things the state constitution or state legislature says they can do and must conform to any requirements or limitations on those powers that are contained in the enabling acts. Parts three and four examine in more detail the main programs and agencies at the federal level as well as Iowa’s state and local levels and the roles they play in national and state water policy.

Bump time-frequency toolbox: a toolbox for time-frequency oscillatory bursts extraction in electrophysiological signals

Background: oscillatory activity, which can be separated in background and oscillatory burst pattern activities, is supposed to be representative of local synchronies of neural assemblies. Oscillatory burst events should consequently play a specific functional role, distinct from background EEG activity – especially for cognitive tasks (e.g. working memory tasks), binding mechanisms and perceptual dynamics (e.g. visual binding), or in clinical contexts (e.g. effects of brain disorders). However extracting oscillatory events in single trials, with a reliable and consistent method, is not a simple task. Results: in this work we propose a user-friendly stand-alone toolbox, which models in a reasonable time a bump time-frequency model from the wavelet representations of a set of signals. The software is provided with a Matlab toolbox which can compute wavelet representations before calling automatically the stand-alone application. Conclusion: The tool is publicly available as a freeware at the address: http:// www.bsp.brain.riken.jp/bumptoolbox/toolbox_home.html

Food Indicators and Their Relationship with 10 to 12 Year-olds' Subjective Well-Being

This study aimed to test subjective indicators designed to analyze the role food plays in children’s lives, explore children’s personal well-being, and evaluate the relationship between these two phenomena. It was conducted on 371 children aged 10 to 12 by means of a selfadministered questionnaire. Results showed a marked interest in food on the part of children, who consider taste and health the most important indicators when it comes to eating. They demonstrated a high level of personal well-being, measured using Cummins & Lau’s adapted version of the Personal Well- Being Index–School Children (PWI-SC) (2005), overall life satisfaction (OLS) and satisfaction with various life domains (friends, family, sports, food and body). Regression models were conducted to explain satisfaction with food, taking as independent variables the interest children have in food, the importance they give to different reasons for eating, scores from the PWI-SC, OLS and satisfaction with various life domains. In the final model, it was found that OLS, health indicators, satisfaction with health from the PWI-SC and satisfaction with your body contribute to explaining satisfaction with food. The results obtained suggest that satisfaction with food is a relevant indicator in the exploration of children’s subjective well-being, calling into question the widespread belief that these aspects are of exclusive interest to adults. They also seem to reinforce the importance of including food indicators in any study aimed at exploring the well-being of the 10 to 12 year-old population.

Urotensin-II System in Genetic Control of Blood Pressure and Renal Function.

Urotensin-II controls ion/water homeostasis in fish and vascular tone in rodents. We hypothesised that common genetic variants in urotensin-II pathway genes are associated with human blood pressure or renal function. We performed family-based analysis of association between blood pressure, glomerular filtration and genes of the urotensin-II pathway (urotensin-II, urotensin-II related peptide, urotensin-II receptor) saturated with 28 tagging single nucleotide polymorphisms in 2024 individuals from 520 families; followed by an independent replication in 420 families and 7545 unrelated subjects. The expression studies of the urotensin-II pathway were carried out in 97 human kidneys. Phylogenetic evolutionary analysis was conducted in 17 vertebrate species. One single nucleotide polymorphism (rs531485 in urotensin-II gene) was associated with adjusted estimated glomerular filtration rate in the discovery cohort (p = 0.0005). It showed no association with estimated glomerular filtration rate in the combined replication resource of 8724 subjects from 6 populations. Expression of urotensin-II and its receptor showed strong linear correlation (r = 0.86, p<0.0001). There was no difference in renal expression of urotensin-II system between hypertensive and normotensive subjects. Evolutionary analysis revealed accumulation of mutations in urotensin-II since the divergence of primates and weaker conservation of urotensin-II receptor in primates than in lower vertebrates. Our data suggest that urotensin-II system genes are unlikely to play a major role in genetic control of human blood pressure or renal function. The signatures of evolutionary forces acting on urotensin-II system indicate that it may have evolved towards loss of function since the divergence of primates.

El doblatge i la subtitulació de The Nightmare before Christmas: una anàlisi contrastiva de les dues grans modalitats de la traducció audiovisual

Aquest treball es proposa analitzar la traducció del doblatge i la subtitulació d'un text audiovisual concret per identificar les tendències i les estratègies de traducció que imperen en cada modalitat. Així mateix, pretén comprovar si a la pràctica es respecten les convencions i normes de la traducció audiovisual

Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge.

Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

Mechanical properties of viral capsids

Viruses are known to tolerate wide ranges of pH and salt conditions and to withstand internal pressures as high as 100 atmospheres. In this paper we investigate the mechanical properties of viral capsids, calling explicit attention to the inhomogeneity of the shells that is inherent to their discrete and polyhedral nature. We calculate the distribution of stress in these capsids and analyze their response to isotropic internal pressure (arising, for instance, from genome confinement and/or osmotic activity). We compare our results with appropriate generalizations of classical (i.e., continuum) elasticity theory. We also examine competing mechanisms for viral shell failure, e.g., in-plane crack formation vs radial bursting. The biological consequences of the special stabilities and stress distributions of viral capsids are also discussed.

Water Planning Law and Government, November 2008

Water planning efforts typically identify problems and needs. But simply calling attention to issues is usually not enough to spur action; the end result of many well-intentioned planning efforts is a report that ends up gathering dust on a shelf. Vague recommendations like “Water conservation measures should be implemented” usually accomplish little by themselves as they don’t assign responsibility to anyone. Success is more likely when an implementation strategy — who can and should do what — is developed as part of the planning process. The more detailed and specific the implementation strategy, the greater the chance that something will actually be done.

Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

OBJECTIVE: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS AND RESULTS: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)). CONCLUSIONS: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib.

Several cancer treatments are shifting from traditional, time-limited, nonspecific cytotoxic chemotherapy cycles to continuous oral treatment with specific protein-targeted therapies. In this line, imatinib mesylate, a selective tyrosine kinases inhibitor (TKI), has excellent efficacy in the treatment of chronic myeloid leukemia. It has opened the way to the development of additional TKIs against chronic myeloid leukemia, including nilotinib and dasatinib. TKIs are prescribed for prolonged periods, often in patients with comorbidities. Therefore, they are regularly co-administered along with treatments at risk of drug-drug interactions. This aspect has been partially addressed so far, calling for a comprehensive review of the published data. We review here the available evidence and pharmacologic mechanisms of interactions between imatinib, dasatinib, and nilotinib and widely prescribed co-medications, including known inhibitors or inducers of cytochromes P450 or drug transporters. Information is mostly available for imatinib mesylate, well introduced in clinical practice. Several pharmacokinetic aspects yet remain insufficiently investigated for these drugs. Regular updates will be mandatory and so is the prospective reporting of unexpected clinical observations.