Multi-faceted functions of secretory IgA at mucosal surfaces.

Secretory IgA (SIgA) plays an important role in the protection and homeostatic regulation of intestinal, respiratory, and urogenital mucosal epithelia separating the outside environment from the inside of the body. This primary function of SIgA is referred to as immune exclusion, a process that limits the access of numerous microorganisms and mucosal antigens to these thin and vulnerable mucosal barriers. SIgA has been shown to be involved in avoiding opportunistic pathogens to enter and disseminate in the systemic compartment, as well as tightly controlling the necessary symbiotic relationship existing between commensals and the host. Clearance by peristalsis appears thus as one of the numerous mechanisms whereby SIgA fulfills its function at mucosal surfaces. Sampling of antigen-SIgA complexes by microfold (M) cells, intimate contact occurring with Peyer's patch dendritic cells (DC), down-regulation of inflammatory processes, modulation of epithelial, and DC responsiveness are some of the recently identified processes to which the contribution of SIgA has been underscored. This review aims at presenting, with emphasis at the biochemical level, how the molecular complexity of SIgA can serve these multiple and non-redundant modes of action.

An Automatic Approach for Learning and Tuning Gaussian Interval Type-2 Fuzzy Membership Functions Applied to Lung CAD Classification System

The potential of type-2 fuzzy sets for managing high levels of uncertainty in the subjective knowledge of experts or of numerical information has focused on control and pattern classification systems in recent years. One of the main challenges in designing a type-2 fuzzy logic system is how to estimate the parameters of type-2 fuzzy membership function (T2MF) and the Footprint of Uncertainty (FOU) from imperfect and noisy datasets. This paper presents an automatic approach for learning and tuning Gaussian interval type-2 membership functions (IT2MFs) with application to multi-dimensional pattern classification problems. T2MFs and their FOUs are tuned according to the uncertainties in the training dataset by a combination of genetic algorithm (GA) and crossvalidation techniques. In our GA-based approach, the structure of the chromosome has fewer genes than other GA methods and chromosome initialization is more precise. The proposed approach addresses the application of the interval type-2 fuzzy logic system (IT2FLS) for the problem of nodule classification in a lung Computer Aided Detection (CAD) system. The designed IT2FLS is compared with its type-1 fuzzy logic system (T1FLS) counterpart. The results demonstrate that the IT2FLS outperforms the T1FLS by more than 30% in terms of classification accuracy.

Natural killer cell receptor-repertoire and functions after induction therapy by polyclonal rabbit anti-thymocyte globulin in unsensitized kidney transplant recipients.

Polyclonal rabbit anti-thymocyte globulin (rATG) is widely used in solid organ transplantation (SOT) as induction therapy or to treat corticosteroid-resistant rejection. In vivo, the effect of rATG on natural killer (NK) cells has not been studied. These cells are of particular relevance after SOT because classical immunosuppressive drugs do not inhibit or even can activate NK cells. A cohort of 20 recipients at low immunological risk, that had been receiving rATG as induction therapy, was analyzed for receptor repertoire, cytotoxicity and capacity of NK cells to secrete IFN-γ before kidney transplantation and at different time points thereafter. NK cells expressed fewer killer-cell immunoglobulin-like receptors (KIR), fewer activating receptors NKG2D, but more inhibitory receptor NKG2A compatible with an immature phenotype in the first 6 months post transplantation. Both cytotoxicity of NK cells and the secretion of IFN-γ were preserved over time after transplantation.

Value and prices in Russian economic thought (1890-1920)

The subject "Value and prices in Russian economic thought (1890--1920)" should evoke several names and debates in the reader's mind. For a long time, Western scholars have been aware that the Russian economists Tugan-Baranovsky and Bortkiewicz were active participants to the Marxian transformation problem, that the mathematical models of Dmitriev prefigured forthcoming neoricardian based models, and that many Russian economists were either supporting the Marxian labour theory of value or being revisionists. Moreover, these ideas were preparing the ground for Soviet planning. Russian scholars additionally knew that this period was the time of introduction of marginalism in Russia, and that, during this period, economists were active in thinking the relation of ethics with economic theory. All these issues are well covered in the existing literature. But there is a big gap that this dissertation intends to fill. The existing literature handles these pieces separately, although they are part of a single, more general, history. All these issues (the labour theory of value, marginalism, the Marxian transformation problem, planning, ethics, mathematical economics) were part of what this dissertation calls here "The Russian synthesis". The Russian synthesis (in the singular) designates here all the attempts at synthesis between classical political economy and marginalism, between labour theory of value and marginal utility, and between value and prices that occurred in Russian economic thought between 1890 and 1920, and that embraces the whole set of issues evoked above. This dissertation has the ambition of being the first comprehensive history of that Russian synthesis. In this, this contribution is unique. It has always surprised the author of the present dissertation that such a book has not yet been written. Several good reasons, both in terms of scarce availability of sources and of ideological restrictions, may accounted for a reasonable delay of several decades. But it is now urgent to remedy the situation before the protagonists of the Russian synthesis are definitely classified under the wrong labels in the pantheon of economic thought. To accomplish this task, it has seldom be sufficient to gather together the various existing studies on aspects of this story. It as been necessary to return to the primary sources in the Russian language. The most important part of the primary literature has never been translated, and in the last years only some of them have been republished in Russian. Therefore, most translations from the Russian have been made by the author of the present dissertation. The secondary literature has been surveyed in the languages that are familiar (Russian, English and French) or almost familiar (German) to the present author, and which are hopefully the most pertinent to the present investigation. Besides, and in order to increase the acquaintance with the text, which was the objective of all this, some archival sources were used. The analysis consists of careful chronological studies of the authors' writings and their evolution in their historical and intellectual context. As a consequence, the dissertation brings new authors to the foreground - Shaposhnikov and Yurovsky - who were traditionally confined to the substitutes' bench, because they only superficially touched the domains quoted above. In the Russian synthesis however, they played an important part of the story. As a side effect, some authors that used to play in the foreground - Dmitriev and Bortkiewicz - are relegated to the background, but are not forgotten. Besides, the dissertation refreshes the views on authors already known, such as Ziber and, especially, Tugan-Baranovsky. The ultimate objective of this dissertation is to change the opinion that one could have on "value and prices in Russian economic thought", by setting the Russian synthesis at the centre of the debates.

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study.

BACKGROUND: Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. METHODS: Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5 log reduction). RESULTS: Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). CONCLUSIONS: In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

The functions of sleep.

Here we report on The Satellite Symposium on Sleep Function that was held in Lausanne during 6(th) FENS forum and brought together neuroscientists from basic and clinical sleep research. We illustrate the principal questions that arose during this interdisciplinary gathering and introduce the contents of nine review articles on aspects of sleep that are contained in this Special Issue of the European Journal of Neuroscience.

When performance-approach goals predict academic achievement and when they do not: A social value approach

Research on achievement goal promotion at University has shown that performance-approach goals are perceived as a means to succeed at University (high social utility) but are not appreciated (low social desirability). We argue that such a paradox could explain why research has detected that performance-approach goals consistently predict academic grades. First-year psychology students answered a performance-approach goal scale with standard, social desirability and social utility instructions. Participants' grades were recorded at the end of the semester. Results showed that the relationship between performance-approach goals and grades was inhibited by the increase of these goals' social desirability and facilitated by the increase of their social utility, revealing that the predictive validity of performance-approach goals depend on social value.

Value of sTREM-1, procalcitonin and CRP as laboratory parameters for postmortem diagnosis of sepsis.

OBJECTIVES: Triggering receptor expressed on myeloid cells-1 (TREM-1) was reported to be up-regulated in various inflammatory diseases as well as in bacterial sepsis. Increased cell-surface TREM-1 expression was also shown to result in marked plasma elevation of the soluble form of this molecule (sTREM-1) in patients with bacterial infections. In this study, we investigated sTREM-1, procalcitonin and C-reactive protein in postmortem serum in a series of sepsis-related fatalities and control individuals who underwent medico-legal investigations. sTREM-1 was also measured in pericardial fluid and urine. METHODS: Two study groups were prospectively formed, a sepsis-related fatalities group and a control group. The sepsis-related fatalities group consisted of sixteen forensic autopsy cases. Eight of these had a documented clinical diagnosis of sepsis in vivo. The control group consisted of sixteen forensic autopsy cases with various causes of death. RESULTS: Postmortem serum sTREM-1 concentrations were higher in the sepsis group with a mean value of 173.6 pg/ml in septic cases and 79.2 pg/ml in control individuals. The cutoff value of 90 pg/ml provided the best sensitivity and specificity. Pericardial fluid sTREM-1 values were higher in the septic group, with a mean value of 296.7 pg/ml in septic cases and 100.9 pg/ml in control individuals. The cutoff value of 135 pg/ml provided the best sensitivity and specificity. Mean urine sTREM-1 concentration was 102.9 pg/ml in septic cases and 89.3 pg/ml in control individuals. CONCLUSIONS: Postmortem serum sTREM-1, individually considered, did not provide better sensitivity and specificity than procalcitonin in detecting sepsis. However, simultaneous assessment of procalcitonin and sTREM-1 in postmortem serum can be of help in clarifying contradictory postmortem findings. sTREM-1 determination in pericardial fluid can be an alternative to postmortem serum in those situations in which biochemical analyses are required and blood collected during autopsy proves insufficient.

Functions of peroxisome proliferator-activated receptors (PPAR) in skin homeostasis.

The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor family. Three isotypes (PPAR alpha, PPAR beta or delta, and PPAR gamma) with distinct tissue distributions and cellular functions have been found in vertebrates. All three PPAR isotypes are expressed in rodent and human skin. They were initially investigated for a possible function in the establishment of the permeability barrier in skin because of their known function in lipid metabolism in other cell types. In vitro studies using specific PPAR agonists and in vivo gene disruption approaches in mice indeed suggest an important contribution of PPAR alpha in the formation of the epidermal barrier and in sebocyte differentiation. The PPAR gamma isotype plays a role in stimulating sebocyte development and lipogenesis, but does not appear to contribute to epidermal tissue differentiation. The third isotype, PPAR beta, regulates the late stages of sebaceous cell differentiation, and is the most effective isotype in stimulating lipid production in these cells, both in rodents and in humans. In addition, PPAR beta activation has pro-differentiating effects in keratinocytes under normal and inflammatory conditions. Finally, preliminary studies also point to a potential role of PPAR in hair follicle growth and in melanocyte differentiation. By their diverse biological effects on cell proliferation and differentiation in the skin, PPAR agonists or antagonists may offer interesting opportunities for the treatment of various skin disorders characterized by inflammation, cell hyperproliferation, and aberrant differentiation.

Signalling, mating success and paternal investment in sticklebacks (Gasterosteus aculeatus): A theoretical model

I present an optimisation model that links paternal investment, male display and female choice. Although deviced for sticklebacks, it readily applies to other fish with male guarding behaviour. It relies on a few basic assumptions on the ways hatching success depends on paternal investment and clutch size, and male survival on paternal investment and signaling. Paternal investment is here a state-dependent decision, and signal a condition-dependent handicap by which males inform females of how much they are willing to invest. Series of predictions are derived on female and male breeding strategies, including optimal levels of signaling and paternal investment as functions of clutch size, own condition, and residual reproductive value, as well as alternative strategies such as egg kleptoparasitism. Some predictions already have empirical support, for which the present model provides new interpretations. Other might readily be tested, e.g. by simple clutch-size manipulations.

Unique and conserved functions of B cell-activating factor of the TNF family (BAFF) in the chicken.

The chicken represents the best-characterized animal model for B cell development in the so-called gut-associated lymphoid tissue (GALT) and the molecular processes leading to B cell receptor diversification in this species are well investigated. However, the mechanisms regulating B cell development and homeostasis in GALT species are largely unknown. Here we investigate the role played by the avian homologue of B cell-activating factor of the tumor necrosis factor family (BAFF). Flow cytometric analysis showed that the receptor for chicken B cell-activating factor of the tumor necrosis factor family (chBAFF) is expressed by mature and immature B cells. Unlike murine and human BAFF, chBAFF is primarily produced by B cells both in peripheral lymphoid organs and in the bursa of Fabricius, the chicken's unique primary lymphoid organ. In vitro and in vivo studies revealed that chBAFF is required for mature B cell survival. In addition, in vivo neutralization with a decoy receptor led to a reduction of the size and number of B cell follicles in the bursa, demonstrating that, in contrast to humans and mice, in chickens BAFF is also required for the development of immature B cells. Collectively, we show that chBAFF has phylogenetically conserved functions in mature B cell homeostasis but displays unique and thus far unknown properties in the regulation of B cell development in birds.

Quantitative Assessment of Handwriting Evidence: The Value of the Shape of the Letter "A"

To provide a quantitative support to the handwriting evidence evaluation, a new method was developed through the computation of a likelihood ratio based on a Bayesian approach. In the present paper, the methodology is briefly described and applied to data collected within a simulated case of a threatening letter. Fourier descriptors are used to characterise the shape of loops of handwritten characters "a" of the true writer of the threatening letter, and: 1) with reference characters "a" of the true writer of the threatening letter, and then 2) with characters "a" of a writer who did not write the threatening letter. The findings support that the probabilistic methodology correctly supports either the hypothesis of authorship or the alternative hypothesis. Further developments will enable the handwriting examiner to use this methodology as a helpful assistance to assess the strength of evidence in handwriting casework.