Covalent homodimers of murine secretory component induced by epitope substitution unravel the capacity of the polymeric Ig receptor to dimerize noncovalently in the absence of IgA ligand.

Recombinant secretory immunoglobulin A containing a bacterial epitope in domain I of the secretory component (SC) moiety can serve as a mucosal delivery vehicle triggering both mucosal and systemic responses (Corthésy, B., Kaufmann, M., Phalipon, A., Peitsch, M., Neutra, M. R., and Kraehenbuhl, J.-P. (1996) J. Biol. Chem. 271, 33670-33677). To load recombinant secretory IgA with multiple B and T epitopes and extend its biological functions, we selected, based on molecular modeling, five surface-exposed sites in domains II and III of murine SC. Loops predicted to be exposed at the surface of SC domains were replaced with the DYKDDDDK octapeptide (FLAG). Another two mutants were obtained with the FLAG inserted in between domains II and III or at the carboxyl terminus of SC. As shown by mass spectrometry, internal substitution of the FLAG into four of the mutants induced the formation of disulfide-linked homodimers. Three of the dimers and two of the monomers from SC mutants could be affinity-purified using an antibody to the FLAG, mapping them as candidates for insertion. FLAG-induced dimerization also occurred with the polymeric immunoglobulin receptor (pIgR) and might reflect the so-far nondemonstrated capacity of the receptor to oligomerize. By co-expressing in COS-7 cells and epithelial Caco-2 cells two pIgR constructs tagged at the carboxyl terminus with hexahistidine or FLAG, we provide the strongest evidence reported to date that the pIgR dimerizes noncovalently in the plasma membrane in the absence of polymeric IgA ligand. The implication of this finding is discussed in terms of IgA transport and specific antibody response at mucosal surfaces.

Factor shares, the price markup, and the elasticity of substitution between capital and labor

[spa] La participación del trabajo en la renta nacional es constante bajo los supuestos de una función de producción Cobb-Douglas y competencia perfecta. En este artículo se relajan estos supuestos y se investiga si el comportamiento no constante de la participación del trabajo en la renta nacional se explica por (i) una elasticidad de sustitución entre capital y trabajo no unitaria y (ii) competencia no perfecta en el mercado de producto. Nos centramos en España y los U.S. y estimamos una función de producción con elasticidad de sustitución constante y competencia imperfecta en el mercado de producto. El grado de competencia imperfecta se mide a través del cálculo del price markup basado en laaproximación dual. Mostramos que la elasticidad de sustitución es mayor que uno en España y menor que uno en los US. También mostramos que el price markup aleja la elasticidad de sustitución de uno, lo aumenta en España, lo reduce en los U.S. Estos resultados se utilizan para explicar la senda decreciente de la participación del trabajo en la renta nacional, común a ambas economías, y sus contrastadas sendas de capital.

Les traitements de l'ostéoporose (à l'exception de la substitution hormonale et de ses dérivés) [Treatment of osteoporosis (with the exception of hormone replacement and its derivates]

Calcium and vitamin D supplementation are warranted for the treatment of osteoporosis, when other specific drugs are used. Vitamin D supplementation is necessary when the plasma level of 25-hydroxy-vitamin D is below 30 nmol/l (12 pg/l) in order to avoid any increase of the plasma parathyroid hormone level. Bisphosphonates are the most widely drugs used. Recent advances will provide patients with a more convenient therapeutically equivalent alternative: the once-weekly oral dosing regimen and probably the possibility to give infusions at intervals of up to one year. Parathyroid hormone administered subcutaneously daily produced a dramatic increase of trabecular and cortical bone mineral density, and an important decrease of vertebral and nonvertebral fracture risk. Strontium is a new original drug, which stimulates bone formation, and inhibits bone resorption. It significantly improves trabecular and cortical bone mass. Calcitonin not only prevents the recurrence of vertebral fractures, but possibly could decrease hip fractures risk. Hydrochlorothiazide preserves the bone mineral density, and decreases nonvertebral fracture risk, as showed in epidemiological studies. Large clinical trials with statins therapy in appropriate populations are required to find out whether these drugs have any role in preventing fractures.

Formica pratensis (Hyménoptères: Formicidae) dans le canton de Vaud: état des peuplements et importance des talus de routes comme milieu de substitution.

Formica pratensis (Hyménoptères Formicidae) figure sur la liste rouge des espèces menacées de Suisse. Cette espèce de fourmis des bois colonise les milieux herbacés ouverts comme les prés et prairies sèches peu exploitées, les talus bien exposés. Face à la raréfaction de ces habitats liée à l'intensification de l'agriculture, elle colonise de plus en plus souvent les talus herbeux en bordure de routes. Afin de mieux comprendre la situation actuelle de l'espèce et ses besoins en milieux naturels, nous avons mené une étude à large échelle dans le cnaton de Vaud (Suisse). F.pratensis se rencontre sur l'ensemble du territoire, principalement en dessous de 800 m, mais elle ne semble plus aussi fréquente qu'autrefois. F.pratensis recherche surtout des stations en pente bien exposées au soleil et avec une végétation assez ouverte. De tels milieux se faisant de plus en plus rares dans le paysage agricole moderne, les talus de route apparaissent souvent comme une alternative (ou milieu de subsitution) pour F.pratensis. les importantes perturbations (pollution, fauche répétitive, pauvreté du milieu) ne permettent toutefois pas aux sociétés de fourmis de se développer pleinement et la survie de l'espèce passe par la sauvegarde d'autres milieux ouverts exploités extensivement. Grâce aux données collectées, un suivi comparatif des populations pourra être effectuée dans les années à venir

Carbon Stocks in Compartments of Soil Organic Matter 31 Years after Substitution of Native Cerrado Vegetation by Agroecosystems

ABSTRACT Changes in carbon stocks in different compartments of soil organic matter of a clayey Latossolo Vermelho Distrófico (Typic Haplustox), caused by the substitution of native savanna vegetation (cerrado sensu stricto) by agroecosystems, were assessed after 31 years of cultivation. Under native vegetation, a stock of 164.5 Mg ha-1 C was estimated in the 0.00-1.00 m layer. After 31 years of cultivation, these changes in soil C stocks were detected to a depth of 0.60 m. In the case of substitution of cerrado sensu stricto by no-tillage soybean-corn rotation, a reduction of at least 11 % of the soil C pools was observed. However, the adoption of no-tillage as an alternative to tillage with a moldboard plow (conventional system) reduced CO2 emissions by up to 12 %.

Factor shares, the price markup, and the elasticity of substitution between capital and labor

[spa] La participación del trabajo en la renta nacional es constante bajo los supuestos de una función de producción Cobb-Douglas y competencia perfecta. En este artículo se relajan estos supuestos y se investiga si el comportamiento no constante de la participación del trabajo en la renta nacional se explica por (i) una elasticidad de sustitución entre capital y trabajo no unitaria y (ii) competencia no perfecta en el mercado de producto. Nos centramos en España y los U.S. y estimamos una función de producción con elasticidad de sustitución constante y competencia imperfecta en el mercado de producto. El grado de competencia imperfecta se mide a través del cálculo del price markup basado en laaproximación dual. Mostramos que la elasticidad de sustitución es mayor que uno en España y menor que uno en los US. También mostramos que el price markup aleja la elasticidad de sustitución de uno, lo aumenta en España, lo reduce en los U.S. Estos resultados se utilizan para explicar la senda decreciente de la participación del trabajo en la renta nacional, común a ambas economías, y sus contrastadas sendas de capital.

Management of hepatitis C virus (HCV) infection in drug substitution programs.

BACKGROUND: In Switzerland, intravenous drug use (IDU) accounts for 80% of newly acquired hepatitis C virus (HCV) infections. Early HCV treatment has the potential to interrupt the transmission chain and reduce morbidity/mortality due to decompensated liver cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug substitution programs are often insufficiently screened and treated. OBJECTIVE/METHODS: With the aim to improve HCV management in IDUs, we conducted a cross sectional chart review in three opioid substitution programs in St. Gallen (125 methadone and 71 heroin recipients). Results were compared with another heroin substitution program in Bern (202 patients) and SCCS/SHCS data. RESULTS: Among the methadone/heroin recipients in St. Gallen, diagnostic workup of HCV was better than expected: HCV/HIV-status was unknown in only 1% (2/196), HCV RNA was not performed in 9% (13/146) of anti-HCV-positives and the genotype missing in 15% (12/78) of HCV RNA-positives. In those without spontaneous clearance (two thirds), HCV treatment uptake was 23% (21/91) (HIV-: 29% (20/68), HIV+: 4% (1/23)), which was lower than in methadone/heroin recipients and particularly non-IDUs within the SCCS/SHCS, but higher than in the, mainly psychiatrically focussed, heroin substitution program in Bern (8%). Sustained virological response (SVR) rates were comparable in all settings (overall: 50%, genotype 1: 35-40%, genotype 3: two thirds). In St. Gallen, the median delay from the estimated date of infection (IDU start) to first diagnosis was 10 years and to treatment was another 7.5 years. CONCLUSIONS: Future efforts need to focus on earlier HCV diagnosis and improvement of treatment uptake among patients in drug substitution programs, particularly if patients are HIV-co-infected. New potent drugs might facilitate the decision to initiate treatment.

Molecular substitution rate increases in myrmecophilous lycaenid butterflies (Lepidoptera)

Is species diversification driven by neutral- or niche-based processes? Butterflies of the Lycaenidae family have developed mutualistic interactions with ants. This biotic requirement increased the spatial fragmentation of populations of lower effective population size (Ne) compared with autonomous species. The nearly neutral theory predicts that species with smaller Ne should fix more mutations because of the increased strength of drift. Taking into account the phylogenetic relatedness among species, this study shows that species with a stronger dependence on ants displayed more intra-specific Single Nucleotide Polymorphisms compared with species with low or no myrmecophily. This phenomenon can cause more pronounced genetic differentiation between populations and could ultimately promote speciation in a similar manner as on physical islands. The large species diversity observed in this family could be the consequence of this neutral process enhancing the diversification of lineages.