Differential heat shock gene hsp70-1 response to toxicants revealed by in vivo study of lungs in transgenic mice

in Cell Stress & Chaperones (2002), 7(4), 387-395

Members of heat shock proteins (Hsp70) family have been considered to respond to a large variety of stressful conditions. But it was suggested that, in pulmonary cells, Hsp response depends more closely ... [more ▼]

Members of heat shock proteins (Hsp70) family have been considered to respond to a large variety of stressful conditions. But it was suggested that, in pulmonary cells, Hsp response depends more closely on the type of stimulus. The lungs are critical organs potentially subjected to air pollution affecting respiratory function and, therefore, these organs are of particular interest with regard to the stress response. To investigate the stress dependence of Hsp70 response in lungs, we created transgenic mice where the firefly luciferase reporter gene is under the control of the murine hsp70-1 promoter and exposed them to different sublethal toxic conditions. For each condition, the level of transgene induction and pulmonary toxicity were assessed. We found that hsp70-1 promoter was stimulated by heat shock and Cadmium but not by ozone, paraquat, and parathion, even if these chemicals induced respiratory distress and lung inflammation. Similar observations were made when expression of the endogenous hsp70-1 gene was analyzed, indicating that our transgenic model was accurately detecting hsp70-1 induction. Thereby, it appeared that hsp70-1 response is selective and depends on signaling pathways triggered by the toxicants rather than by their pathologic toxicity per se. Furthermore, because all the chemicals used in our study have been previously described to increase the level of oxidative stress, it indicates that there is no direct and simple correlation between hsp70-1 response and the level of oxidative stress, but more specific oxidative patterns should be involved in Hsp regulation. [less ▲]

Differential impacts of plant interactions on herbaceous species recruitment: disentangling factors controlling emergence, survival and growth of seedlings

in Oecologia (2009)

Recruitment is a crucial event in the plant life cycle that is very sensitive to interaction with established vegetation. Based on a large comparative experiment, we tested the hypothesis that the ... [more ▼]

Recruitment is a crucial event in the plant life cycle that is very sensitive to interaction with established vegetation. Based on a large comparative experiment, we tested the hypothesis that the components of recruitment –emergence time and rate, seedling survival and biomass – differ in response to plant-plant interactions during recruitment. The consequences for the population are predicted with a simple demographic model assessing the response of seed production. In a common garden experiment, we recorded the recruitment of four target species in an individual-based survey protocol. A total of 7,680 seeds were sown within 20 neigbourhoods, consisting of 19 mono-specific herbaceous stands and a control treatment without vegetation. We measured transmitted light, temperature and moisture at soil surface to characterise the environmental conditions within neighbourhoods. The mean height of neighbours controlled temperature buffering and light interception and thus depicted the interaction gradient. Emergence rate and time increased with neighbour height in two of the four target species, while seedling survival and biomass significantly decreased with neighbour height in three and all four target species, respectively. We recorded a shift in seedling neighbour interactions under the tallest neighbours that largely favoured emergence but strongly depressed seedling survival and biomass. The components of recruitment were predicted to differ in their impact on later adult performance. Biomass strongly contributed to predicted seed production in three target species, and emergence had an equal or greater impact on a fourth species. These results confirm the fundamental role of plant-plant interactions in the recruitment of herbaceous species through a complex combination of habitat amelioration, which facilitates emergence and light competition, which in turn limits seedling survival and biomass. [less ▲]

Differential involvement of the hMRE11/hRAD50/NBS1 complex, BRCA1 and MLH1 in NF-kappa B activation by camptothecin and X-ray

in Oncogene (2003), 22(38), 6090-6099

Camptothecin (CPT) and X-ray (XR) generate double-strand breaks (DSB) that can be processed by homologous or nonhomologous recombination. We studied the participation of proteins involved in recombination ... [more ▼]

Camptothecin (CPT) and X-ray (XR) generate double-strand breaks (DSB) that can be processed by homologous or nonhomologous recombination. We studied the participation of proteins involved in recombination pathways and cell cycle control in the signal transduction between DNA damage and NF-kappaB. Cells harbouring mutated NBS, hMRE11, BRCA1 or MLH1 were analysed. NBS- and hMRE11-deficient cells present a classical kinetic of NF-kappaB induction after camptothecin treatment. When DSB are generated by XR, NBS-deficient cells exhibit a delayed and strongly reduced level of NF-kappaB induction, whereas the hMRE11 mutated cells do not induce NF-kappaB at all. This indicates an important role of the hMRE11/hRAD50/NBS complex in the signal transduction initiated by XR. In HCC1937 cells that express a truncated version of BRCA1, XR induces a very rapid and transient NF-kappaB activation, whereas CPT leads to a delayed activation suggesting that BRCA1 modulates the transduction pathways in different manners after these two stresses. Finally, we found that a proficient MMR pathway is essential to the NF-kappaB activation after both CPT and XR. These results indicate that DSB originating from XR or CPT do not induce NF-kappaB in a unique way. MMR participates in both cascades, whereas the hMRE11/hRAD50/NBS trimer is specifically involved in the response elicited by XR. [less ▲]

Differential isotopic turnover (C and N) detected in Antarctic scavenger amphipods

Conference (2010, September)

Differential item functioning among multiple groups: an outlier identification approach

Scientific conference (2010, June 07)

Differential item functioning (DIF) has received increasing focus in the past decades. Recently, Magis and De Boeck (2010) proposed to identify differentially functioning items as outliers in a one ... [more ▼]

Differential item functioning (DIF) has received increasing focus in the past decades. Recently, Magis and De Boeck (2010) proposed to identify differentially functioning items as outliers in a one-dimensional space of DIF measures, using robust statistical tools for outlier identification. The purpose of this talk is to present an extension of this approach for the case of more than one focal group. In this multiple group framework, items can be characterized by multiple vectors of DIF measures, one for each focal group, so that a multivariate DIF space is obtained. DIF items can then be identified as outliers in this multivariate space, based on robust multivariate estimators of location and dispersion. The MCD (Minimum Covariance Determinant) estimator is shown to be adequate for this purpose. A major asset of the method that it can rely on existing DIF indices to define the DIF vectors, and that it does not need a purification step. Alternatively, it can be used to determine on an anchor set. The method will be illustrated by an example about calculator effects on mathematics test items. [less ▲]

Differential location of nucleic acids within interchromatin granule clusters.

in European Journal of Cell Biology (1993), 62(2), 259-69

We have examined in great detail the distribution of nucleic acids within interchromatin granule clusters in different cell types by means of various immunocytochemical approaches. Using the in situ ... [more ▼]

We have examined in great detail the distribution of nucleic acids within interchromatin granule clusters in different cell types by means of various immunocytochemical approaches. Using the in situ polyadenylate nucleotidyl transferase-immunogold technique for RNA detection or anti-RNA antibodies, we decisively demonstrate the presence of appreciable amount of RNA in clusters of interchromatin granules of untreated cells. Neither the in situ terminal deoxynucleotidyl transferase-immunogold technique nor anti-DNA antibodies, nor the in situ nick-translation technique for DNA detection have revealed any DNA in the interchromatin granule clusters. However, dispersed chromatin sensitive to DNase I are found at the borders and in the close vicinity of interchromatin granule clusters. The results indicate that interchromatin granule clusters should not be nuclear structures directly involved in RNA transcription but rather in some other steps of RNA metabolism. [less ▲]

Differential operators acting on tensor densities

Doctoral thesis (1998)

Differential pathomechanisms of epidermal necrolytic blistering diseases.

in International Journal of Molecular Medicine (2002), 10(6), 695-9

Staphylococcal scalded skin syndrome (SSSS) results from the effect of exfoliative-toxins produced by staphylococcal strains. The disease affects predominantly children, and is rare in adults. We report ... [more ▼]

Staphylococcal scalded skin syndrome (SSSS) results from the effect of exfoliative-toxins produced by staphylococcal strains. The disease affects predominantly children, and is rare in adults. We report two cases of the adult type of SSSS. Corticotherapy, chronic alcohol abuse and epilepsy-related immune changes might have been predisposing factors in these patients. The immunopathological characteristics of the inflammatory cell infiltrate in adults SSSS have not been thoroughly explored so far in the literature. Biopsies from 2 patients with bullous SSSS skin were studied by means of immunochemistry using a panel of 10 antibodies directed to FXIIIa, CD15, CD31, CD45R0, CD50, CD54, CD62E, CD95, CD106, and L1-protein, respectively. Cutaneous biopsies from related blistering diseases were compared. They included drug-induced toxic epidermal necrolysis (TEN), bullous impetigo and superficial pemphigus. A dense cell infiltrate composed of granulocytes (CD15+), macrophages (L1 protein+) and memory T cells (CD45R0+) and a strong expression of ICAM-3 (CD50) were present in the epidermis. CD95+ keratinocytes were lining the intraepidermal blisters. Type I dermal dendrocytes (Factor XIIIa+) were numerous and plump in the dermis. Bullous impetigo exhibited the same pattern of inflammatory cells, but with a lower density in type I dermal dendrocytes. TEN differed from SSSS by both the absence of CD15+ granulocytes and a stronger expression of the pro-apoptotic CD95 antigen in the epidermis. In superficial pemphigus, CD95 antigen was not expressed, and CD15+ granulocytes, CD45R0+ lymphocytes and L1 protein+ monocytes were much less numerous. It is concluded that the specific binding of SSSS-induced exotoxins to the desmosomes alters the keratinocyte metabolism leading to an inflammatory reaction followed by focal apoptosis. Our findings are in line with the concept that SSSS exotoxins might be superantigens. A common pathomechanism leading to epidermal destruction is likely operative in SSSS and bullous impetigo. The inflammatory cell composition in TEN and superficial pemphigus markedly differs from that in SSSS. [less ▲]

Differential production of cytokines and activation of NF-kappa B in HPV-transformed keratinocytes

in Virology (2002), 298(2), 271-285

We have proposed that chronic infection of keratinocytes by HPV modifies the expression of potentially important cytokines by interfering with the NF-kappaB signal pathway We evaluated the constitutive ... [more ▼]

We have proposed that chronic infection of keratinocytes by HPV modifies the expression of potentially important cytokines by interfering with the NF-kappaB signal pathway We evaluated the constitutive and IL-1beta-induced expression of GM-CSF and TNF-alpha and the expression/activity of NF-kappaB in HPV+ and HPV- cell lines. Despite the enhanced expression of the functional components of the NF-kappaB signaling pathway in HPV+ cell lines by a mechanism implicating the HPV oncoprotein E6, the constitutive activity of NF-kappaB and the expression of GM-CSF/TNF-alpha were significantly reduced relative to the HPV- cell line and normal keratinocytes. In contrast, we observed a superactivation of NF-kappaB activity after IL-1beta stimulation, a strong and transient induction of GM-CSF/TNF-alpha mRNA, but undetectable levels of secreted proteins in HPV+ cell lines. Our data demonstrate that E6 modulates the NF-kappaB signaling pathway and suggest that other HPV proteins also interfere with GM-CSF/TNF-alpha expression by transcriptional and/or posttranscriptional mechanisms. (C) 2002 Elsevier Science (USA). [less ▲]

Differential Regulation of Chondrocyte Metabolism by Oncostatin M and Interleukin-6

in Osteoarthritis and Cartilage (2004), 12(10), 801-10

OBJECTIVE: To determine the effects of interleukin (IL)-6 and oncostatin M (OSM) added separately or in combination with IL-1beta on human osteoarthritic (OA) chondrocytes in alginate beads. DESIGN: Human ... [more ▼]

OBJECTIVE: To determine the effects of interleukin (IL)-6 and oncostatin M (OSM) added separately or in combination with IL-1beta on human osteoarthritic (OA) chondrocytes in alginate beads. DESIGN: Human chondrocytes were isolated from OA cartilage and cultured in alginate beads for 12 days, in the absence or in the presence of increasing amounts of IL-6 (20-500ng/ml) with its soluble receptor or OSM (0.1-10ng/ml) and with or without IL-1beta (1.7ng/ml). Aggrecan (AGG), transforming growth factor-beta1 (TGF-beta1), stromelysin-1 [matrix metalloprotease (MMP)-3], tissue inhibitor of metalloproteinases-1 (TIMP-1), macrophage inflammatory protein-1 beta (MIP-1beta), IL-6 and IL-8 productions were assayed by specific enzyme amplified sensitivity immunoassays. Prostaglandin (PG)E(2) was measured by a specific radioimmunoassay and nitrite (NO(2)(-)) by a spectrophotometric method based upon the Griess reaction. RESULTS: OSM, but not IL-6, decreased basal AGG and TGF-beta1 synthesis. Although IL-6 stimulated basal TIMP-1 production, it did not significantly modify MMP-3/TIMP-1 ratio. In contrast, 10ng/ml OSM highly increased TIMP-1 production, and decreased by half the ratio MMP-3/TIMP-1. IL-1beta highly stimulated *NO, IL-8, IL-6, MIP-1beta and PGE(2) synthesis but decreased AGG and TGF-beta1 production. Neither IL-6 nor OSM modulated IL-1beta-inhibitory effect on AGG production. IL-6, but not OSM, reversed IL-1beta-induced TGF-beta1 inhibition. At 1-10ng/ml, OSM significantly decreased IL-1beta-stimulated IL-8, MIP-1beta, PGE(2) and *NO production but amplified IL-1beta stimulating effect on IL-6 production. IL-6 had no effect on these parameters. CONCLUSIONS: OSM and IL-6, two glycoprotein 130 binding cytokines, show different activity profiles on OA chondrocytes, indicating that these cytokines could play different roles in the OA disease process. [less ▲]