Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index.

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.

Macbride nature recreation area : hiking and cross-country ski trails, 1987.

This brochure contains information on the hiking and cross-country ski trails in the Macbride Nature Recreation Area located 15 minutes north of Iowa City in Johnson County.

National Identity and the Preference for State Opting-Out in the Basque Country

We argue that preferences for secession are the expression of a common unobserved mechanisms determining national identity. This paper examines the hypothesis of independence of both preferences for secession (independent Euskadi) and Basque national identity in the light of Akerloff and Kranton (2000). We deal with psychological determinants of individuals' national identity formation as well as those that influence the propensity of individuals to support the secession of their perceived ¿imagined community¿ or nation.. We undertake econometric survey analysis for the Basque Country using a bivariate probit model and publicly available data from the Spanish Centre for Sociological Research. Our results provide robust evidence of a common determination of national identity and political preferences for the secession of the Basque Country consistently with Akerloff and Kranton model.

Decomposing Cross-Country Gaps in Obesity and Overweight: Does the Social Environment Matter?

[cat] Una qüestió clau sobre la producció de salut relativament poc explorada es refereix a la influència dels factors socioeconòmics i mediambientals sobre el pes i l’obesitat. Aquesta problemàtica adquireix particular rellevància quan es comparen dos països Mediterranis com Itàlia i Espanya. És interessant adonar-se que l’obesitat a Espanya és 5 punts percentual més elevada al 2003 mentre que a l’any 1990 era aproximadament la mateixa en ambdós països. Aquesta article presenta una descomposició no lineal dels gaps o diferencials en taxes de sobrepès (índex de massa corporal – IMC- entre 25 i 29.9 9 kg/m2), obesitat classe 1 (IMC≥30 kg/m2) i classe 2 (IMC≥35 kg/m2) entre Espanya i Itàlia per gènere i grups d’edat. En explicar aquests gaps entre països aïllem les influències dels estils de vida, els efectes socioeconòmics i els mediambientals. Els nostres resultats indiquen que quan no es controla pels efectes mediambientals (efectes de grup o ‘peer effects’) els hàbits alimentaris i el nivell educatiu són els principals predictors del gaps totals entre països (36-52%), si bé aquests dos factors exerceixen un impacte diferenciat segons gènere i edat. Un tant paradoxalment, quan controlem pels efectes de grup aquests predictors perden la seva capacitat explicativa i els efectes de grup passen a explicar entre el 46-76% dels gaps en sobrepès i obesitat i mostren un patró creixent amb l’edat.

Identification and potential origin of invasive clawed frogs Xenopus (Anura: Pipidae) in Sicily based on mitochondrial and nuclear DNA

African clawed frogs of the widespread polytypic species Xenopus laevis Daudin, 1802 (ranging large parts of sub-Saharan Africa) have been spreading since the 1940s, and have established reproductive populations in Europe, Asia and the Americas, where they can have negative impact as competitors of native amphibians and as disease vectors for chytridomycosis or ranaviruses. Here we use two mitochondrial (cytochrome b, 16S rDNA) and one nuclear (RAG 1: Recombination Associated Gene 1) DNA markers to infer the potential origin of invasive clawed frogs from Sicily that represent the largest invasive population in Europe. Identical mtDNA haplotypes match with those of Xenopus laevis, and Sicilian clawed frogs very probably belong to a lineage from the Cape Region of South Africa, most likely originating from a laboratory stock. Nuclear data support this conclusion. Identical mtDNA sequences (cyt b, 16S) of frogs sampled across their range in Sicily suggest the occurrence of a single source population and a potential bottleneck at their release, but faster evolving multilocus nuclear data (microsatellites, SNPs) on the population genetics would be important in the future to better support this hypothesis

The biomechanic origin of sprint performance enhancement after one-week creatine supplementation.

In order to test whether an improvement of maximal sprinting speed after creatine (Cr) supplementation was due to the increase of stride frequency (SF), stride length (SL) or both, 7 subjects ran 4 consecutive sprints after 1 week of placebo or Cr supplementation. SF and SL were assessed by a triaxial accelerometer. Compared to the placebo, Cr induced an increase of running speed (+1.4% p < 0.05) and SF (+1.5%, p < 0.01), but not of SL. The drop in performance following repeated sprints was partially prevented by Cr. In conclusion, exogenous Cr enhanced sprinting performance by increasing SF. This result may be related to the recent findings of shortening in muscular relaxation time after Cr supplementation.

Metabolic syndrome according to different definitions in a rapidly developing country of the African region

Rapport de synthèseLe syndrome métabolique représente un ensemble de facteurs de risque métaboliques souvent présents simultanément et il est associé à un risque accru de développer des maladies cardiovasculaires. La prevalence du syndrome métabolique est à la hausse au niveau mondial comme cela a souvent été documenté, en particulier dans les pays développés. Pourtant, les données concernant le syndrome métabolique dans les pays de la région sub-saharienne restent rares.Au cours des dernières années, plusieurs définitions du syndrome métabolique ont été formulées, dont celle du 'National Cholesterol Education Program Adult Treatment Panel III', celle de 1 Organisation Mondiale de la Santé et celle du 'International Diabetes Federation'. Parmi les controverses au sujet du syndrome métabolique persiste la question de l'utilité de rechercher la présence du syndrome métabolique chez les patients diabétiques, étant donné que la présence d'un diabète en soit suffit pour identifier un individu à haut risque de faire un événement cardiovasculaire.L'objectif de ce travail de thèse a été de déterminer la prévalence du syndrome métabolique selon les trois définitions majeures mentionnées ci-dessus, grâce à une étude de population transversale, réalisée aux Seychelles en 2004 dans un échantillon représentatif de la population âgée de 24-65 ans (n=1255, taux de participation de 80.3%). L'intérêt d'examiner cette question dans ce pays était d'obtenir des informations dans un pays en transition épidémiologique.Les résultats de ce travail montrent que la prévalence du syndrome métabolique aux Seychelles est élevée, quelque soit la définition utilisée. Selon la définition utilisée, cette prévalence était d'environ 25% chez les hommes et variant entre 25 et 35% chez les femmes.Cependant, malgré des prévalences semblables selon ces trois définitions, la concordance entre ces définitions n'était pas bonne, impliquant que ces différentes définitions classifient, à un certain degré, des individus différents comme étant porteurs du syndrome métabolique.En outre, la plupart (environ 80%) des individus diabétiques avaient un syndrome métabolique. Après exclusion des individus diabétiques, la prévalence du syndrome métabolique dans la population est réduite d'environ un tiers, à environ 20-25%.Ces résultats montrent que, d'une part, le fardeau de maladie dû au syndrome métabolique aux Seychelles, un pays en voie de développement, est considérable. Cette observation peut potentiellement s'appliquer à d'autres pays à un stade de développement semblable. Cela renforce le besoin de mettre en oeuvre des stratégies de santé publique afin de cibler les causes de ces désordres métaboliques, tels que le surpoids et la sédentarité. D'un point de vue du diagnostic, les trois définitions du syndrome métabolique semblent classifier un nombre semblable de personnes atteints du syndrome métabolique dans cette population. Par contre, la relativement mauvaise concordance entre ces définitions - certaines personnes identifiés comme porteurs du syndrome métabolique selon une définition ne le sont pas selon une autre - confirme la nécessité de clarifier la signification de ces différentes définitions et/ou éventuellement de développer une définition unifiée et fiable du syndrome métabolique.

Macular and retinal dysfunction of unknown origin in adults with normal fundi: evidence for an autoimmune pathophysiology.

Here we report the discovery of and phenotypic characterization of a retinal disorder of unknown origin in adults using clinical, electrophysiological and psychophysical techniques, and to seek the presence of circulating retinal autoantibodies in the sera of these patients. Sixteen patients were identified with progressive bilateral visual loss over a period of months. Ten of the patients were male, and the average age was 55.3 years (range from 43 to 76 years). Known causes such as carcinoma-associated retinopathy, acute zonal occult outer retinopathy and hereditary cone dystrophy appeared unlikely. Investigations included electrophysiology, fundus autofluorescence imaging and psychophysical tests. The sera of these patients were analyzed with indirect immunocytochemistry and Western immunoblot analysis on murine (BALB/c) retinal tissue for the presence of retinal autoantibodies. Bilateral visual loss and photophobia progressed over a period of months to years (average 28.7 months, range 3-67) and subsequently stabilized. No abnormality was observed by biomicroscopy, angiography or autofluorescence imaging. Electrophysiology indicated predominant cone-system dysfunction, either macular or generalized, and post-phototransduction involvement in 9 patients (56%). Photopic and scotopic visual fields and dark adaptation kinetics showed both cone and rod system involvement in all cases. Heterogeneous immunohistochemical staining patterns were seen with the sera of these patients as compared with controls. A majority of the affected patients (9/15) stained with an antinuclear pattern. The retinal autoantibodies from the sera of most patients reacted with the retinal proteins of molecular weight between 34 and 40 kDa. The aetiology of this distinctive retinal disorder therefore appears to be mediated through an autoimmune mechanism.

A dual functional origin of transfer in the ICEclc genomic island of Pseudomonas knackmussii B13.

Genomic islands (GEIs) are large DNA segments, present in most bacterial genomes, that are most likely acquired via horizontal gene transfer. Here, we study the self-transfer system of the integrative and conjugative element ICEclc of Pseudomonas knackmussii B13, which stands model for a larger group of ICE/GEI with syntenic core gene organization. Functional screening revealed that unlike conjugative plasmids and other ICEs ICEclc carries two separate origins of transfer, with different sequence context but containing a similar repeat motif. Conjugation experiments with GFP-labelled ICEclc variants showed that both oriTs are used for transfer and with indistinguishable efficiencies, but that having two oriTs results in an estimated fourfold increase of ICEclc transfer rates in a population compared with having a single oriT. A gene for a relaxase essential for ICEclc transfer was also identified, but in vivo strand exchange assays suggested that the relaxase processes both oriTs in a different manner. This unique dual origin of transfer system might have provided an evolutionary advantage for distribution of ICE, a hypothesis that is supported by the fact that both oriT regions are conserved in several GEIs related to ICEclc.

Identification of human IKK-2 inhibitors of natural origin (Part II): in Silico prediction of IKK-2 inhibitors in natural extracts with known anti-inflammatory activity.

Human inhibitor NF-κB kinase 2 (hIKK-2) is the primary component responsible for activating NF-κB in response to various inflammatory stimuli. Thus, synthetic ATP-competitive inhibitors for hIKK-2 have been developed as anti-inflammatory compounds. We recently reported a virtual screening protocol (doi:10.1371/journal.pone.0016903) that is able to identify hIKK-2 inhibitors that are not structurally related to any known molecule that inhibits hIKK-2 and that have never been reported to have anti-inflammatory activity. In this study, a stricter version of this protocol was applied to an in-house database of 29,779 natural products annotated with their natural source. The search identified 274 molecules (isolated from 453 different natural extracts) predicted to inhibit hIKK-2. An exhaustive bibliographic search revealed that anti-inflammatory activity has been previously described for: (a) 36 out of these 453 extracts; and (b) 17 out of 30 virtual screening hits present in these 36 extracts. Only one of the remaining 13 hit molecules in these extracts shows chemical similarity with known synthetic hIKK-2 inhibitors. Therefore, it is plausible that a significant portion of the remaining 12 hit molecules are lead-hopping candidates for the development of new hIKK-2 inhibitors.

On the origin of the North Pacific arcs

We present a new hypothesis that relates global plate tectonics to the formation of marginal basins, island arcs, spreading ridges and arc-shaped mountain belts around the North Pacific Ocean. According to our model, the ellipsoidal-shaped Paleogene basins of the South China Sea, Parece-Vela Basin, Shikoku Basin, Sea of Japan and the Sea of Okhotsk in addition to those of the North American Cordillera can be attributed to the change in plate convergence direction at 42 Ma between the Indoaustralian and Eurasian plates. The new direction of convergence was parallel to the eastern continental margin of Asia and resulted in widespread extension perpendicular to this margin and to the western margin of North America. Both margins form part of a circle parallel to the Indoaustralian-Eurasian direction of convergence.