Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs

Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.     

A ground‐level ozone forecasting model for Santiago,Chile

A physically based model for ground‐level ozone forecasting is evaluated for Santiago, Chile. The model predicts the daily peak ozone concentration, with the daily rise of air temperature as input variable; weekends and rainy days appear as interventions. This model was used to analyse historical data, using the Linear Transfer Function/Finite Impulse Response (LTF/FIR) formalism; the Simultaneous Transfer Function (STF) method was used to analyse several monitoring stations together. Model evaluation showed a good forecasting performance across stations—for low and high ozone impacts—with power of detection (POD) values between 70 and 100%, Heidke's Skill Scores between 40% and 70% and low false alarm rates (FAR). The model consistently outperforms a pure persistence forecast. Model performance was not sensitive to different implementation options. The model performance degrades for two‐ and three‐days ahead forecast, but is still acceptable for the purpose of developing an environmental warning system at Santiago. Copyright © 2002 John Wiley & Sons, Ltd.     

Abnormal pattern detected in fragile-X patients by pulsed-field gel electrophoresis.

The fragile-X syndrome is the most frequent inherited form of mental retardation, with an incidence of 1 in 1,500 males. It is characterized by the presence of a fragile site at Xq27.3 induced in vitro by folate deprivation or by inhibitors of deoxynucleotide synthesis. Its mode of inheritance is unusual for an X-linked trait, with incomplete penetrance in both males and females. Some phenotypically normal males transmit the mutation to all their daughters who rarely express any symptoms, but penetrance is high in sons and daughters of these carrier women. Genetic and physical mapping of the Xq27-q28 region has confirmed that the disease locus is located at or very near the fragile site. Hypotheses proposed to account for the abnormalities in the inheritance of the disease include sequence rearrangements by meiotic recombination or a mutation that affects reactivation of an inactive X chromosome during differentiation of female germ cells. To detect such rearrangements, or methylation changes that may reflect a locally inactive X chromosome, we used pulsed-field gel analysis of DNA from fragile-X patients with probes close to the fragile-X locus. The probe Do33 (DXS465) detected abnormal patterns in fragile-X patients, but not in normal controls or in non-expressing male transmitters.     

Host cell reactivation of ozone-treated T3 bacteriophage by different strains ofEscherichia coli

Summary Host cell reactivation capacity for ozone T3 phage was determined for differentE. coli strains deficient in one or more of the DNA repair mechanisms. The results indicate that DNA polymerase I appears to play a key role in the repair of damage produced on the DNA by ozone while thelexA gene product seems to play a minor one.This research was sponsored by the National Sciences and Engineering Council of Canada. One of us (PLH) acknowledges a scholarship from the NSERCof Canada.     

Truth and openness: an epistemology for interpretive systemology

Both an ontoepistemology for reductionist modern science (counter-ontoepistemology) and an ontology for interpretive Systemology have been outlined in the two preceding papers in this special issue ofSystems Practice. In the present article, the notion of “truth” is interpreted in terms of both the ontoepistemology of “reductionism” and the ontology of interpretive systemology. Both interpretations are discussed. Such a discussion represents the objective of this paper, that is, to outline the epistemological “face” of the ontoepistemology of interpretive systemology. In order to design that “epistemological face,” the relation between ontology and epistemology must be clarified. Such a relation is seen from the standpoint already provided by the ontology. After the discussion on the notion of truth, the general shape of a systemic-interpretive inquiring process is outlined.     

Un curare d'une Erythrine africaine

Summary An alcaloid C₁₆H₁₉NO₃ has been isolated fromErythrina tholloniana; the iodohydrate of this erythroidine has a melting point of 225°C and 239°C for its chlorhydrate. It has a powerful curare-like action on the frog or on its isolated sciatic-sartorius preparation; at a concentration of less than 1/1,000,000, a complete neuromuscular block is produced: the electrical stimulation of the motor nerve does not produce any contraction, but the muscle reacts by an end-plate potential having the same characteristics (shape, duration, possibility of summation) as the electrical waves produced in the same preparation curarized by ordinary curare or by quaternary ammonium derivatives. Decurarization by veratrine 1/200,000 is accompanied by the same electrical reactions as those which have been described in preparations treated by curare.On mammals, the alcaloid has little curariform activity; on the isolated phrenic-diaphragm preparation of the rat, incomplete block was produced at a concentration of 1/5000.     

Comments on “aggregation of equivalence relations” by P. C. Fishburn and A. Rubinstein

The theorem of the paper Aggregation of Equivalence Relations, by Fishburn and Rubinstein, states a result already known. This theorem improves a result from Mirkin (1975) and appears as a corollary occurring in Leclerc (1984).

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Resume L'unique théorème de l'article Aggregation of Equivalence Relations de Fishburn et Rubinstein est déja connu. Il améliore, en fait, un résultat de Mirkin (1975) et apparait en tant que corollaire dans Leclerc (1984).

     

Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model

Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.     

The median procedure for n-trees

Let (X,d) be a metric space The functionM:X ^k 2 ^x defined by is the minimum } is called themedian procedure and has been found useful in various applications involving the notion of consensus Here we present axioms that characterizeM whenX is a certain class of trees (hierarchical classifications), andd is the symmetric difference metricWe would like to thank the referees and Editor for helpful comments