A single point mutation in the pore region of the epithelial Na+ channel changes ion selectivity by modifying molecular sieving.

The epithelial Na+ channel (ENaC) belongs to a new class of channel proteins called the ENaC/DEG superfamily involved in epithelial Na+ transport, mechanotransduction, and neurotransmission. The role of ENaC in Na+ homeostasis and in the control of blood pressure has been demonstrated recently by the identification of mutations in ENaC beta and gamma subunits causing hypertension. The function of ENaC in Na+ reabsorption depends critically on its ability to discriminate between Na+ and other ions like K+ or Ca2+. ENaC is virtually impermeant to K+ ions, and the molecular basis for its high ionic selectivity is largely unknown. We have identified a conserved Ser residue in the second transmembrane domain of the ENaC alpha subunit (alphaS589), which when mutated allows larger ions such as K+, Rb+, Cs+, and divalent cations to pass through the channel. The relative ion permeability of each of the alphaS589 mutants is related inversely to the ionic radius of the permeant ion, indicating that alphaS589 mutations increase the molecular cutoff of the channel by modifying the pore geometry at the selectivity filter. Proper geometry of the pore is required to tightly accommodate Na+ and Li+ ions and to exclude larger cations. We provide evidence that ENaC discriminates between cations mainly on the basis of their size and the energy of dehydration.

Sequence homologies within the 5' end region of the estrogen-controlled vitellogenin gene in Xenopus and chicken.

In oviparous vertebrates vitellogenin, the precursor of the major yolk proteins, is synthesized in the liver of mature females under the control of estrogen. We have established the organization and primary structure of the 5' end region of the Xenopus laevis vitellogenin A2 gene and of the major chicken vitellogenin gene. The first three homologous exons have exactly the same length in both species, namely 53, 21 and 152 nucleotides, and present an overall sequence homology of 60%. In both species, the 5'-non-coding region of the vitellogenin mRNA measures only 13 nucleotides, nine of which are conserved. In contrast, the corresponding introns of the Xenopus and the chicken vitellogenin gene show no significant sequence homology. Within the 500 nucleotides preceding the 5' end of the genes, at least six blocks with sequence homologies of greater than 70% were detected. It remains to be demonstrated which of these conserved sequences, if any, are involved in the hormone-regulated expression of the vitellogenin genes.

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.

Deep crustal electromagnetic structure of Bhuj earthquake region (India) and its implications

The existence of fluids and partial melt in the lower crust of the seismically active Kutch rift basin (on the western continental margin of India) owing to underplating has been proposed in previous geological and geophysical studies. This hypothesis is examined using magnetotelluric (MT) data acquired at 23 stations along two profiles across Kutch Mainland Uplift and Wagad Uplift. A detailed upper crustal structure is also presented using twodimensional inversion of MT data in the Bhuj earthquake (2001) area. The prominent boundaries of reflection in the upper crust at 5, 10 and 20 km obtained in previous seismic reflection profiles correlate with conductive structures in our models. The MT study reveals 1-2 km thick Mesozoic sediments under the Deccan trap cover. The Deccan trap thickness in this region varies from a few meters to 1.5 km. The basement is shallow on the northern side compared to the south and is in good agreement with geological models as well as drilling information. The models for these profiles indicate that the thickness of sediments would further increase southwards into the Gulf of Kutch. Significant findings of the present study indicate 1) the hypocentre region of the earthquake is devoid of fluids, 2) absence of melt (that is emplaced during rifting as suggested from the passive seismological studies) in the lower crust and 3) a low resistive zone in the depth range of 5-20 km. The present MT study rules out fluidsand melt (magma) as the causative factors that triggered the Bhuj earthquake. The estimated porosity value of 0.02% will explain 100-500 ohm·m resistivity values observed in the lower crust. Based on the seismic velocities and geochemical studies, presence of garnet is inferred. The lower crust consists of basalts - probably generated by partial melting of metasomatised garnet peridotite at deeper depths in the lithosphere - and their composition might be modified by reaction with the spinel peridotites.

Plastinated Ethmoidal Region : I. Preparation and Applications in Clinical Teaching.

Ethmoidal regions weer prepared and dissected to demonstrate regional sinus anatomy and endoscopic surgery approaches from six human heads. After perparation, the specimens were plastinated using the standard S10 technique. A CT-scan of each ethmoidal block was performed before and after preparation of the block to access shrinkage. The plastinated specimens were successfully introduced into clinical teaching of sinus anatomy and surgery. One advantage of using these specimens is their long-lasting preservation without deterioration of the tissue. The specimens were well suited for comparative radiographic and ondoscopic studies, and the CT-scans allowed an exact measurement of tissue shrinkage due to plastination. Increaseed tissue rigidity and shrionkage due to plastination has to be taken into account for subsequent endoscopic observation.

Methods for Determining Frequency- and Region-Dependent Relationships Between Estimated LFPs and BOLD Responses in Humans

The relationship between electrophysiological and functional magnetic resonance imaging (fMRI) signals remains poorly understood. To date, studies have required invasive methods and have been limited to single functional regions and thus cannot account for possible variations across brain regions. Here we present a method that uses fMRI data and singe-trial electroencephalography (EEG) analyses to assess the spatial and spectral dependencies between the blood-oxygenation-level-dependent (BOLD) responses and the noninvasively estimated local field potentials (eLFPs) over a wide range of frequencies (0-256 Hz) throughout the entire brain volume. This method was applied in a study where human subjects completed separate fMRI and EEG sessions while performing a passive visual task. Intracranial LFPs were estimated from the scalp-recorded data using the ELECTRA source model. We compared statistical images from BOLD signals with statistical images of each frequency of the eLFPs. In agreement with previous studies in animals, we found a significant correspondence between LFP and BOLD statistical images in the gamma band (44-78 Hz) within primary visual cortices. In addition, significant correspondence was observed at low frequencies (<14 Hz) and also at very high frequencies (>100 Hz). Effects within extrastriate visual areas showed a different correspondence that not only included those frequency ranges observed in primary cortices but also additional frequencies. Results therefore suggest that the relationship between electrophysiological and hemodynamic signals thus might vary both as a function of frequency and anatomical region.

Influence of weather, rank, and home advantage on football outcomes in the gulf region.

PURPOSE: The objective of this study was to investigate the effects of weather, rank, and home advantage on international football match results and scores in the Gulf Cooperation Council (GCC) region. METHODS: Football matches (n = 2008) in six GCC countries were analyzed. To determine the weather influence on the likelihood of favorable outcome and goal difference, generalized linear model with a logit link function and multiple regression analysis were performed. RESULTS: In the GCC region, home teams tend to have greater likelihood of a favorable outcome (P < 0.001) and higher goal difference (P < 0.001). Temperature difference was identified as a significant explanatory variable when used independently (P < 0.001) or after adjustment for home advantage and team ranking (P < 0.001). The likelihood of favorable outcome for GCC teams increases by 3% for every 1-unit increase in temperature difference. After inclusion of interaction with opposition, this advantage remains significant only when playing against non-GCC opponents. While home advantage increased the odds of favorable outcome (P < 0.001) and goal difference (P < 0.001) after inclusion of interaction term, the likelihood of favorable outcome for a GCC team decreased (P < 0.001) when playing against a stronger opponent. Finally, the temperature and wet bulb globe temperature approximation were found as better indicators of the effect of environmental conditions than absolute and relative humidity or heat index on match outcomes. CONCLUSIONS: In GCC region, higher temperature increased the likelihood of a favorable outcome when playing against non-GCC teams. However, international ranking should be considered because an opponent with a higher rank reduced, but did not eliminate, the likelihood of a favorable outcome.

No evidence for mutations of CTCFL/BORIS in Silver-Russell syndrome patients with IGF2/H19 imprinting control region 1 hypomethylation.

BACKGROUND: Silver-Russell syndrome (SRS) is a genetically and clinically heterogeneous disease. Although no protein coding gene defects have been reported in SRS patients, approximately 50% of SRS patients carry epimutations (hypomethylation) at the IGF2/H19 imprinting control region 1 (ICR1). Proper methylation at ICR1 is crucial for the imprinted expression of IGF2, a fetal growth factor. CTCFL, a testis-specific protein, has recently been proposed to play a role in the establishment of DNA methylation at the murine equivalent of ICR1. A screen was undertaken to assess whether CTCFL is mutated in SRS patients with hypomethylation, to explore a link between the observed epimutations and a genetic cause of the disease. METHODOLOGY/PRINCIPAL FINDINGS: DNA was obtained from 36 SRS patients with hypomethylation at ICR1. All CTCFL coding exons were sequenced and analyzed for duplications/deletions using both multiplex ligation-dependent probe amplification, with a custom CTCFL probe set, and genomic qPCR. Novel SNP alleles were analyzed for potential differential splicing in vitro utilizing a splicing assay. Neither mutations of CTCFL nor duplications/deletions were observed. Five novel SNPs were identified and have been submitted to dbSNP. In silico splice prediction suggested one novel SNP, IVS2-66A>C, activated a cryptic splice site, resulting in aberrant splicing and premature termination. In vitro splicing assays did not confirm predicted aberrant splicing. CONCLUSIONS/SIGNIFICANCE: As no mutations were detected at CTCFL in the patients examined, we conclude that genetic alterations of CTCFL are not responsible for the SRS hypomethylation. We suggest that analysis of other genes involved in the establishment of DNA methylation at imprinted genes, such as DNMT3A and DNMT3L, may provide insight into the genetic cause of hypomethylation in SRS patients.

La vegetacion de los arrozales en la region mediterranea

En 1945 J. BORJA, estudiando la flora de la Ribera valenciana, observó la presencia en los arrozales de varias especies particulares que, estudiadas detenidamente, fueron determinadas como Ammannia coccínea Rottb., A. verticillata Rottb., Bergia aquatica Roxb., etc. (v. FONT QUER, 1946; BORJA, 1950). Estas especies, alguna de las cuales era ya conocida de los arrozales de Portugal, no se habían indicado todavía de los que tan gran importancia alcanzan en el levante peninsular, en los cuales sin embargo deben existir desde tiempo algo antiguo, según acredita el hecho de que la indicada Bergia, por ejemplo, que los viejos campesinos conocen de toda la vida, posea incluso nombre popular (en Valencia la llaman alfabegueta, BORJA, 1. c ) .

Speciation of naturally-accumulated uranium in an organic-rich soil of an alpine region (Switzerland)

Very high concentrations of uranium (up to 4000 ppm) were found in a natural soil in the Dischma valley, an alpine region in the Grisons canton in Switzerland. The goal of this study was to examine the redox state and the nature of uranium binding in the soil matrix in order to understand the accumulation mechanism. Pore water profiles collected from Dischma soil revealed the establishment of anoxic conditions with increasing soil depth. A combination of chemical extraction methods and spectroscopy was applied to characterize the redox state and binding environment of uranium in the soil. Bicarbonate extraction under anoxic conditions released most of the uranium indicating that uranium occurs predominantly in the hexavalent form. Surprisingly, the uranium redox state did not vary greatly as a function of depth. X-ray absorption near edge spectroscopy (XANES), confirmed that uranium was present as a mixture of U(VI) and U(IV) with U(VI) dominating. Sequential extractions of soil samples showed that the dissolution of solid organic matter resulted in the simultaneous release of the majority of the soil uranium content (>95%). Extended X-ray absorption fine structure (EXAFS) spectroscopy also revealed that soil-associated uranium in the soil matrix was mainly octahedrally coordinated, with an average of 1.7 axial (at about 1.76 Å) and 4.6 to 5.3 equatorial oxygen atoms (at about 2.36 Å) indicating the dominance of a uranyl-like (UO22+) structure presumably mixed with some U(IV). An additional EXAFS signal (at about 3.2 Å) identified in some spectra suggested that uranium was also bound (via an oxygen atom) to a light element such as carbon, phosphorus or silicon. Gamma spectrometric measurements of soil profiles failed to identify uranium long-life daughter products in the soil which is an indication that uranium originates elsewhere and was transported to its current location by water. Finally, it was found that the release of uranium from the soil was significantly promoted at very low pH values (pH 2) and increased with increasing pH values (between pH 5 and 9).