Cation Transport Coupled to ATP Hydrolysis By the (Na, K)-ATPase : an integrated, animated model

An Adobe (R) animation is presented for use in undergraduate Biochemistry courses, illustrating the mechanism of Na+ and K+ translocation coupled to ATP hydrolysis by the (Na, K)-ATPase, a P-2c-type ATPase, or ATP-powered ion pump that actively translocates cations across plasma membranes. The enzyme is also known as an E-1/E-2-ATPase as it undergoes conformational changes between the E-1 and E-2 forms during the pumping cycle, altering the affinity and accessibility of the transmembrane ion-binding sites. The animation is based on Horisberger's scheme that incorporates the most recent significant findings to have improved our understanding of the (Na, K)-ATPase structure function relationship. The movements of the various domains within the (Na, K)-ATPase alpha-subunit illustrate the conformational changes that occur during Na+ and K+ translocation across the membrane and emphasize involvement of the actuator, nucleotide, and phosphorylation domains, that is, the "core engine" of the pump, with respect to ATP binding, cation transport, and ADP and P-i release.

Industrial nanoparticle application : representative survey among Swiss companies shows low usage and basic protection means

Manufactured nanoparticles are introduced into industrial processes, but they are suspected to cause similar negative health effects as ambient particles. The poor knowledge about the scale of this introduction did not allow global risk analysis so far. In 2006 a targeted telephone survey among Swiss companies (1) showed the usage of nanoparticles in a few selected companies but did not provide data to extrapolate on the totality of the Swiss workforce. To gain this kind of information a layered representative questionnaire survey among 1'626 Swiss companies was conducted in 2007. Data was collected about the number of potentially exposed persons in the companies and their protection strategy. The response rate was 58.3%. An expected number of 586 companies (95%−confidence interval 145 to 1'027) was shown by this study to use nanoparticles in Switzerland. Estimated 1'309 (1'073 to 1'545) workers do their job in the same room as a nanoparticle application. Personal protection was shown to be the predominant type of protection means. Companies starting productions with nanomaterials need to consider incorporating protection measures into the plans. This will not only benefit the workers' health, but will also likely increase the competitiveness of the companies. Technical and organisational protection means are not only more cost−effective on the long term, but are also easier to control. Guidelines may have to be designed specifically for different industrial applications, including fields outside nanotechnology, and adapted to all sizes of companies.

Oral flurbiprofen metabolic ratio assessment using a single-point dried blood spot.

We investigated whether a single blood measurement using the minimally invasive technique of a finger prick to draw a blood sample of 5 µl (to yield a dried blood spot (DBS)) is suitable for the assessment of flurbiprofen (FLB) metabolic ratio (MR). Ten healthy volunteers who had been genotyped for CYP2C9 were recruited as subjects. They received FLB alone in session 1 and FLB with fluconazole in session 2. In session 3, the subjects were pretreated for 4 days with rifampicin and received FLB with the last dose of rifampicin on day 5. Plasma and DBS samples were obtained between 0 and 8 h after FLB administration, and urine was collected during the 8 h after administration. The pharmacokinetic profiles of the drugs were comparable in DBS and plasma. FLB's apparent clearance values decreased by 35% in plasma and DBS during session 2 and increased by 75% in plasma and by 30% in DBS during session 3. Good correlations were observed between MRs calculated from urine, plasma, and DBS samples.

Basic Skill Assessment Requirements for Placement into Courses and Programs at Iowa Community Colleges, September 26, 2007

Iowa Department of Education surveyed Iowa’s 15 community colleges to gain information about each institution’s basic skill assessment requirements for placement into courses and programs. The survey asked what basic skill assessment(s) each institution uses, whether developmental course placement was mandatory, and what scores students needed to obtain to avoid being required or urged to take developmental courses in math, science, and reading. Additionally, staff members at each college were asked what the testing requirements are for students’ enrolled full time in high school that are taking community college classes.

Pulse oximetry and transcutaneous oxygen tension for detection of hypoxemia in critically ill infants and children.

We tested the performance of transcutaneous oxygen monitoring (TcPO2) and pulse oximetry (tcSaO2) in detecting hypoxia in critically ill neonatal and pediatric patients. In 54 patients (178 data sets) with a mean age of 2.4 years (range 1 to 19 years), arterial saturation (SaO2) ranged from 9.5 to 100%, and arterial oxygen tension (PaO2) from 16.4 to 128 mmHg. Linear correlation analysis of pulse oximetry vs measured SaO2 revealed an r value of 0.95 (p less than 0.001) with an equation of y = 21.1 + 0.749x, while PaO2 vs tcPO2 showed a correlation coefficient of r = 0.95 (p less than 0.001) with an equation of y = -1.04 + 0.876x. The mean difference between measured SaO2 and tcSaO2 was -2.74 +/- 7.69% (range +14 to - 29%) and the mean difference between PaO2 and tcPO2 was +7.43 +/- 8.57 mmHg (range -14 to +49 mmHg). Pulse oximetry was reliable at values above 65%, but was inaccurate and overestimated the arterial SaO2 at lower values. TcPO2 tended to underestimate the arterial value with increasing PaO2. Pulse oximetry had the best sensitivity to specificity ratio for hypoxia between 65 and 90% SaO2; for tcPO2 the best results were obtained between 35 and 55 mmHg PaO2.

Persistent unequal sex ratio in a population of grayling (salmonidae) and possible role of temperature increase.

In some fishes, water chemistry or temperature affects sex determination or creates sex-specific selection pressures. The resulting population sex ratios are hard to predict from laboratory studies if the environmental triggers interact with other factors, whereas in field studies, singular observations of unusual sex ratios may be particularly prone to selective reporting. Long-term monitoring largely avoids these problems. We studied a population of grayling (Thymallus thymallus) in Lake Thun, Switzerland, that has been monitored since 1948. Samples of spawning fish have been caught about 3 times/week around spawning season, and water temperature at the spawning site has been continuously recorded since 1970. We used scale samples collected in different years to determine the average age of spawners (for life-stage specific analyses) and to identify the cohort born in 2003 (an extraordinarily warm year). Recent tissue samples were genotyped on microsatellite markers to test for genetic bottlenecks in the past and to estimate the genetically effective population size (N(e) ). Operational sex ratios changed from approximately 65% males before 1993 to approximately 85% males from 1993 to 2011. Sex ratios correlated with the water temperatures the fish experienced in their first year of life. Sex ratios were best explained by the average temperature juvenile fish experienced during their first summer. Grayling abundance is declining, but we found no evidence of a strong genetic bottleneck that would explain the apparent lack of evolutionary response to the unequal sex ratio. Results of other studies show no evidence of endocrine disruptors in the study area. Our findings suggest temperature affects population sex ratio and thereby contributes to population decline. Persistencia de Proporción de Sexos Desigual en una Población de Tímalos (Salmonidae) y el Posible Papel del Incremento de la Temperatura.

Probabilistic evidential assessment of gunshot residue particle evidence (Part I): likelihood ratio calculation and case pre-assessment using Bayesian networks

Well developed experimental procedures currently exist for retrieving and analyzing particle evidence from hands of individuals suspected of being associated with the discharge of a firearm. Although analytical approaches (e.g. automated Scanning Electron Microscopy with Energy Dispersive X-ray (SEM-EDS) microanalysis) allow the determination of the presence of elements typically found in gunshot residue (GSR) particles, such analyses provide no information about a given particle's actual source. Possible origins for which scientists may need to account for are a primary exposure to the discharge of a firearm or a secondary transfer due to a contaminated environment. In order to approach such sources of uncertainty in the context of evidential assessment, this paper studies the construction and practical implementation of graphical probability models (i.e. Bayesian networks). These can assist forensic scientists in making the issue tractable within a probabilistic perspective. The proposed models focus on likelihood ratio calculations at various levels of detail as well as case pre-assessment.

Trace element distribution among rock-forming minerals from metamorphosed to partially molten basic igneous rocks in a contact aureole (Fuerteventura, Canaries)

Low pressure partial melting of basanitic and ankaramitic dykes gave rise to unusual, zebra-like migmatites, in the contact aureole of a layered pyroxenite-gabbro intrusion, in the root zone of an ocean island (Basal Complex, Fuerteventura, Canary Islands). These migmatites are characterised by a dense network of closely spaced, millimetre-wide leucocratic segregations. Their mineralogy consists of plagioclase (An(32-36)), diopside, biotite, oxides (magnetite, ilmenite), +/-amphibole, dominated by plagioclase in the leucosome and diopside in the melanosome. The melanosome is almost completely recrystallised, with the preservation of large, relict igneous diopside phenocrysts in dyke centres. Comparison of whole-rock and mineral major- and trace-element data allowed us to assess the redistribution of elements between different mineral phases and generations during contact metamorphism and partial melting. Dykes within and outside the thermal aureole behaved like closed chemical systems. Nevertheless, Zr, Hf, Y and REEs were internally redistributed, as deduced by comparing the trace element contents of the various diopside generations. Neocrystallised diopside - in the melanosome, leucosome and as epitaxial phenocryst rims - from the migmatite zone, are all enriched in Zr, Hf, Y and REEs compared to relict phenocrysts. This has been assigned to the liberation of trace elements on the breakdown of enriched primary minerals, kaersutite and sphene, on entering the thermal aureole. Major and trace element compositions of minerals in migmatite melanosomes and leucosomes are almost identical, pointing to a syn- or post-solidus reequilibration on the cooling of the migmatite terrain i.e. mineral-melt equilibria were reset to mineral-mineral equilibria. (C) 2007 Elsevier B.V. All rights reserved.

Validation des SCORES cliniques: notions théoriques et pratiques de base. [Validation of clinical scores: theoretical and practical basic notions].

Chaque jour, le médecin utilise dans sa pratique des scores cliniques. Ces scores sont souvent des aides à la décision médicale. Les étapes de validation des scores cliniques sont par contre souvent méconnues du médecin. Cette revue rappelle les bases théoriques de la validation d'un score clinique et propose des exercices pratiques. [Abstract] Physicians are using clinical scores on a regular basis. These scores are generally helpful in making medical decisions. However, the process of validation of clinical scores is often unknown to the physicians. This paper reviews the theory of validation of clinical scores and proposes practical exercises.

A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.

Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.

Molar substitution and C2/C6 ratio of hydroxyethyl starch: influence of blood coagulation

Résumé Cette étude a démontré l'effet individuel sur la coagulation sanguine humaine des deux principales caractéristiques de la molécule d'hydroxyéthylamidon (HES) : la substitution molaire et le rapport C2/C6. L'analyse par thrombélastographe (TEG®) indique que la molécule de HES dont la substitution molaire est de 0.42 et le rapport C2/C6 de 2.7 a le moins d'effet sur la coagulation sanguine chez l'être humain. Objectifs de l'étude Le développement d'hydroxyéthylamidons (HES) qui ont à la fois peu d'impact sur la coagulation sanguine et une longue persistance intravasculaire est d'un grand intérêt clinique. Une précédente étude in vitro a démontré qu'une solution de HES de haut poids moléculaire et de bas degré de substitution molaire ne compromettait pas plus la coagulation sanguine qu'une solution HES de poids moléculaire moyen (1). La présente étude examine l'effet individuel de la substitution molaire et du rapport C2/C6 d'une solution de HES de haut poids moléculaire (700 kDa) sur la coagulation sanguine. Matériel et méthode Nous avons prélevé du sang chez 30 adultes en bonne santé; le sang a été mélangé avec 6 solutions de HES qui diffèrent par leur degré de substitution molaire (0.42 et 0.51) et leur rapport C2/C6 (2.7, 7 et 14) à trois degrés de dilution : 20%, 40% et 60%. Les échantillons ont ensuite été analysés par thrombélastographe. Les données ont été étudiées par analyse de variance à trois voies pour mesures répétées sur une voie (dilution). Résultats Plus la substitution molaire est élevée, plus la coagulation sanguine est compromise et ce concernant tous les paramètres du TEG® (tous les p sont < à 0.05). La solution HES avec le rapport C2/C6 le plus bas a l'effet le moins prononcé sur le temps r (p<0.001), l'angle α (p=0.003) et l'Index de Coagulation CI (p<0.001) ; on n'a pas observé d'effet sur le temps k (p=0.513) et l'amplitude maximale (p=0.699) concernant ce paramètre. Conclusion L'analyse par thrombélastographe révèle qu'une molécule de HES avec une substitution molaire de 0.42 et un rapport C2/C6 de 2.7 a un effet minimal sur la coagulation sanguine humaine in vitro.

Aggregate stability in soils cultivated with eucalyptus

The objective of this work was to evaluate the aggregate stability of tropical soils under eucalyptus plantation and native vegetation, and assess the relationships between aggregate stability and some soil chemical and physical properties. Argisols, Cambisol, Latosols and Plinthosol within three eucalyptus-cultivated regions, in the states of Espírito Santo, Rio Grande do Sul and Minas Gerais, Brazil, were studied. For each region, soils under native vegetation were compared to those under minimum tillage with eucalyptus cultivation. The aggregate stability was measured using the high-energy moisture characteristic (HEMC) technique, i.e., the moisture release curve at very low suctions. This method compares the resistance of aggregates to slaking on a relative scale from zero to one. Thus, the aggregate stability from different soils and management practices can be directly compared. The aggregate stability ratio was greater than 50% for all soils, which shows that the aggregate stability index is high, both in eucalyptus and native vegetation areas. This suggests that soil management adopted for eucalyptus cultivation does not substantially modify this property. In these soils, the aggregate stability ratio does not show a good relationship with clay or soil organic matter contents. However, soil organic matter shows a positive relationship with clay content and cation exchange capacity.

Correlation of physical and chemical attributes of soil with sugarcane yield

The objective of this work was to evaluate the correlation between sugarcane yield and some physical and chemical attributes of soil. For this, a 42‑ha test area in Araras, SP, Brazil, was used. Soil properties were determined from samples collected at the beginning of the 2003/2004 harvest season, using a regular 100x100 m grid. Yield assessment was done with a yield monitor (Simprocana). Correlation analyses were performed between sugarcane yield and the following soil properties: pH, pH CaCl2, N, C, cone index, clay content, soil organic matter, P, K, Ca, Mg, H+AL, cation exchange capacity, and base saturation. Correlation coefficients were respectively ‑0.05, ‑0.29, 0.33, 0.41, ‑0.27, 0.22, 0.44, ‑0.24, trace, ‑0.06, 0.01, 0.32, 0.14, and 0.04. Correlations of chemical and physical attributes of soil with sugarcane yield are weak, and, per se, they are not able to explain sugarcane yield variation, which suggests that other variables, besides soil attributes, should be analysed.

Systematic study of the temperature dependence of the saturation magnetization in Fe, Fe-Ni and Co-based amorphous alloys

Magnetization versus temperature in the temperature interval 2-200 K was measured for amorphous alloys of three different compositions: Fe 81.5B14.5Si4, Fe40Ni38 Mo4B18, and Co70Fe5Ni 2Mo3B5Si15. The measurements were performed by means of a SQUID (superconducting quantum interference device) magnetometer. The aim was to extract information about the different mechanisms contributing to thermal demagnetization. A powerful data analysis technique based on successive minimization procedures has demonstrated that Stoner excitations of the strong ferromagnetic type play a significant role in the Fe-Ni alloy studied. The Fe-rich and Co-rich alloys do not show a measurable contribution from single-particle excitations.

Transcriptional regulatory patterns of the myelin basic protein and malic enzyme genes by the thyroid hormone receptors alpha1 and beta1.

While there is evidence that the two ubiquitously expressed thyroid hormone (T3) receptors, TRalpha1 and TRbeta1, have distinct functional specificities, the mechanism by which they discriminate potential target genes remains largely unexplained. In this study, we demonstrate that the thyroid hormone response elements (TRE) from the malic enzyme and myelin basic protein genes (METRE and MBPTRE) respectively, are not functionally equivalent. The METRE, which is a direct repeat motif with a 4-base pair gap between the two half-site hexamers binds thyroid hormone receptor as a heterodimer with 9-cis-retinoic acid receptor (RXR) and mediates a high T3-dependent activation in response to TRalpha1 or TRbeta1 in NIH3T3 cells. In contrast, the MBPTRE, which consists of an inverted palindrome formed by two hexamers spaced by 6 base pairs, confers an efficient transactivation by TRbeta1 but a poor transactivation by TRalpha1. While both receptors form heterodimers with RXR on MBPTRE, the poor transactivation by TRalpha1 correlates also with its ability to bind efficiently as a monomer. This monomer, which is only observed with TRalpha1 bound to MBPTRE, interacts neither with N-CoR nor with SRC-1, explaining its functional inefficacy. However, in Xenopus oocytes, in which RXR proteins are not detectable, the transactivation mediated by TRalpha1 and TRbeta1 is equivalent and independent of a RXR supply, raising the question of the identity of the thyroid hormone receptor partner in these cells. Thus, in mammalian cells, the binding characteristics of TRalpha1 to MBPTRE (i.e. high monomer binding efficiency and low transactivation activity) might explain the particular pattern of T3 responsiveness of MBP gene expression during central nervous system development.