Calmodulin kinase IV: expression and function during rat brain development.

The expression of calmodulin kinase IV (CaMKIV) can be induced by the thyroid hormone T3 in a time- and concentration-dependent manner at a very early stage of brain differentiation using a fetal rat telencephalon primary cell culture system which can grow and differentiate under chemically defined conditions (Krebs et al. (1996) J. Biol. Chem. 271, 11055-11058). After the induction of CaMKIV by T3 we examined the influence of prolonged absence of T3 from the culture medium on the expression of CaMKIV. We could demonstrate that after the T3-dependent induction of CaMKIV, omission of the hormone, even for 8 days, from the medium did not downregulate the expression of CaMKIV indicating that different regulatory mechanisms became important for the expression of the enzyme. We further showed that CaMKIV could be involved in the Ca(2+) -dependent expression of the immediate early gene c-fos, probably via phosphorylation of the transcription factor CREB. Convergence of signal transduction pathways on this transcription factor by using different protein kinases may explain the importance of CREB for the regulation of different cellular processes.

Compositional influence on the electrical performance of zinc indium tin oxide transparent thin-film transistors

In this work, zinc indium tin oxide layers with different compositions are used as the active layer of thin film transistors. This multicomponent transparent conductive oxide is gaining great interest due to its reduced content of the scarce indium element. Experimental data indicate that the incorporation of zinc promotes the creation of oxygen vacancies. In thin-film transistors this effect leads to a higher threshold voltage values. The field-effect mobility is also strongly degraded, probably due to coulomb scattering by ionized defects. A post deposition annealing in air reduces the density of oxygen vacancies and improves the fieldeffect mobility by orders of magnitude. Finally, the electrical characteristics of the fabricated thin-film transistors have been analyzed to estimate the density of states in the gap of the active layers. These measurements reveal a clear peak located at 0.3 eV from the conduction band edge that could be attributed to oxygen vacancies.

Treatment of osteitis pubis with on single iv injection of Ibandronate: report of two cases

Objectives: Osteitis pubis is a noninfectious painfulinflammatory disorder of the symphysis pubis. Etiologicfactors are numerous, the most common are: osseousextension of adductor enthesis due to sport overuse,irritation after urological and abdominal procedures, andsystemic inflammatory disorders in particular spondylarthropathies.Many cases are idiopathic. The symptomsconsist of regional chronic mechanical and sometimenocturnal pain. Diagnosis is usually confirmed by eitherbone scintigraphy or by MRI. There are no standardtreatments but conservative approaches including rest andNSAIDS are generally recommended. In 2001, a goodclinical and radiological response of three refractory caseswith 3-6 monthly perfusions of pamidronate was reported(1). Ibandronate is a much more powerful and long-lastingbisphosphonate than pamidronate, and has not yet beenreported in literature to our knowledge in this indication.Materials/Methods: We present two cases of idiopathicorigin: one woman (63 years old) and one man (36 yearsold).The symptoms were present >3 months in the firstpatient and 1 year in the second. The diagnosis wasconfirmed by MRI which showed bone edema on bothsizes of symphysis and in the second case bony erosionsadjacent to the joint were seen. Both cases failed to respondto conservative measures. Both patients received one singledirect iv Injection of 3 mg of Ibandronate.Results: The injections resulted in a rapid (within a fewdays) resolution of pain that lasted more than 6 months inboth patients. No side effects were observed. In the firstcase, an isotope bone scan performed 4 months after theinjection showed no residual uptake. The second patienthad a repeated MRI after 6 months. It demonstrated anattenuation of bone edema compared to the first MRI.Conclusions: IV Ibandronate may constitute a safe andeffective treatment option for patients with refractoryosteitis pubis.Reference: 1: Maksymowych WP, Aaron SL, Russell AS, JRheumatol 28:2754, 2001.Disclosure of Interest: None declared.

Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide.

Adaptive immune responses are initiated when T cells encounter antigen on dendritic cells (DC) in T zones of secondary lymphoid organs. T zones contain a 3-dimensional scaffold of fibroblastic reticular cells (FRC) but currently it is unclear how FRC influence T cell activation. Here we report that FRC lines and ex vivo FRC inhibit T cell proliferation but not differentiation. FRC share this feature with fibroblasts from non-lymphoid tissues as well as mesenchymal stromal cells. We identified FRC as strong source of nitric oxide (NO) thereby directly dampening T cell expansion as well as reducing the T cell priming capacity of DC. The expression of inducible nitric oxide synthase (iNOS) was up-regulated in a subset of FRC by both DC-signals as well as interferon-γ produced by primed CD8+ T cells. Importantly, iNOS expression was induced during viral infection in vivo in both LN FRC and DC. As a consequence, the primary T cell response was found to be exaggerated in Inos(-/-) mice. Our findings highlight that in addition to their established positive roles in T cell responses FRC and DC cooperate in a negative feedback loop to attenuate T cell expansion during acute inflammation.

Correspondance : 1812-1876. IV. 1854-1863 / George Sand

Collection : Bibliothèque contemporaine

Insulin resistance in mice lacking neuronal nitric oxide synthase is related to an alpha-adrenergic mechanism

Rapport de synthèse : Le monoxyde d'azote (NO) joue un rôle important dans la régulation de l'homéostasie du système cardiovasculaire et du glucose. Les souris déficientes pour le gène codant l'isoforme neuronale de la synthase de monoxyde d'azote (nNOS) sont résistantes à l'insuline, mais les mécanismes sous-jacents sont inconnus. Le manque de NO produit par la nNOS pourrait être à l'origine d'une diminution de la perfusion du muscle squelettique et ainsi d'une diminution de l'apport de substrat. Alternativement, le déficit de nNOS normalement hautement exprimé dans le tissu musculaire squelettique pourrait directement y perturber la consommation de glucose. Finalement l'absence de l'action sympatholytique du NO neuronal pourrait diminuer la sensibilité à l'insuline. Afin de tester ces hypothèses nous avons étudié, chez des souris déficientes en nNOS et des souris-contrôle, la consommation corporelle totale de glucose et le flux musculaire squelettique pendant des clamps hyperinsulinémiques euglycémiques in vivo, ainsi que la consommation de glucose dans le muscle squelettique in vitro. De plus nous avons analysé les effets d'une inhibition alpha-adrénergique sur la consommation de glucose pendant les clamps hyperinsulinémiques euglycémiques in vivo. Le taux de perfusion de glucose pendant les clamps était grossièrement 15 pourcent plus bas (P<0.001) chez les souris déficientes en nNOS que chez les souris-contrôle. Cette résistance à l'insuline chez les souris déficientes en nNOS n'était due ni à une stimulation déficiente du flux sanguin musculaire par l'insuline ni à un défaut intrinsèque de la consommation de glucose du muscle (qui étaient comparables dans les deux groupes), mais à un mécanisme alpha-adrénergique, car l'administration de phentolamine rétablissait la sensibilité à l'insuline chez les souris déficientes en nNOS. Ces résultats suggèrent qu'une hyperactivité sympathique, potentiellement due à la perte de l'inhibition neuronale centrale du flux sympathique par le NO provenant de nNOS, contribue à la résistance à l'insuline des souris déficientes en nNOS. Par ailleurs ces résultats tendent à prouver qu'un défaut de production de NO provoquerait une résistance à l'insuline par des mécanismes différents selon l'isoforme de NO synthase déficiente (par exemple chez les souris déficientes pour la forme endothéliale de NO synthase, il a été montré que la résistance à l'insuline est due à un défaut de stimulation de la perfusion musculaire par l'insuline et à un défaut du signalling de l'insuline dans la cellule musculaire squelettique). Chez l'être humain il est établi que les états de résistance à l'insuline sont associés à une synthèse défectueuse et/ou une mauvaise biodisponibilité du NO, ainsi qu'à une hyperactivité sympathique. Nous spéculons que la perte d'inhibition centrale du flux sympathique représente un mécanisme contribuant à la résistance à l'insuline et ses complications cardiovasculaires chez l'être humain.

Noves aportacions al coneixement florístic de l’Empordà - IV = A new contribution to the flora of the Empordà (Catalonia, NE Iberian Peninsula) - IV

En el decurs de les prospeccions florístiques realitzades en els darrers tres anys a les comarques de l’Alt i Baix Empordà, s’han herboritzat diversos tàxons singulars que completen algunes de les aportacions ja publicades anteriorment (Font et al., 1998). En aquest treball se cita per primer cop al Principat la composta Evax lusitanica. La resta detàxons són novetats per a aquestes comarques o bé suposen l’herborització recent d’espècies citades de molt antic que no havien estat indicades darrerament i que en alguns casos suposen les úniques o darreres localitats conegudes a Catalunya

Nitric oxide and the release of lipoprotein lipase from white adipose tissue

Background/Aim: Lipoprotein lipase (LPL) is the main enzyme responsible for the distribution of circulating triacylglycerides in tissues. Its regulation via release from active sites in the vascular endothelium is poorly understood. In a previous study we reported that in response to acute immobilization (IMMO), LPL activity rapidly increases in plasma and decreases in white adipose tissue (WAT) in rats. In other stress situations IMMO triggers a generalized increase in nitric oxide (NO) production. Methods/Results: Here we demonstrate that in rats: 1) in vivo acute IMMO rapidly increases NO concentrations in plasma 2) during acute IMMO the WAT probably produces NO via the endothelial isoform of nitric oxide synthase (eNOS) from vessels, and 3) epididymal WAT perfused in situ with an NO donor rapidly releases LPL from the endothelium. Conclusion: We propose the following chain of events: stress stimulus / rapid increase of NO production in WAT (by eNOS) / release of LPL from the endothelium in WAT vessels. This chain of events could be a new mechanism that promotes the rapid decrease of WAT LPL activity in response to a physiological stimulus.

Differential stress reaction of human colon cells to oleic-acid-stabilized and unstabilized ultrasmall iron oxide nanoparticles.

Therapeutic engineered nanoparticles (NPs), including ultrasmall superparamagnetic iron oxide (USPIO) NPs, may accumulate in the lower digestive tract following ingestion or injection. In order to evaluate the reaction of human colon cells to USPIO NPs, the effects of non-stabilized USPIO NPs (NS-USPIO NPs), oleic-acid-stabilized USPIO NPs (OA-USPIO NPs), and free oleic acid (OA) were compared in human HT29 and CaCo2 colon epithelial cancer cells. First the biophysical characteristics of NS-USPIO NPs and OA-USPIO NPs in water, in cell culture medium supplemented with fetal calf serum, and in cell culture medium preconditioned by HT29 and CaCo₂ cells were determined. Then, stress responses of the cells were evaluated following exposure to NS-USPIO NPs, OA-USPIO NPs, and free OA. No modification of the cytoskeletal actin network was observed. Cell response to stress, including markers of apoptosis and DNA repair, oxidative stress and degradative/autophagic stress, induction of heat shock protein, or lipid metabolism was determined in cells exposed to the two NPs. Induction of an autophagic response was observed in the two cell lines for both NPs but not free OA, while the other stress responses were cell- and NP-specific. The formation of lipid vacuoles/droplets was demonstrated in HT29 and CaCo₂ cells exposed to OA-USPIO NPs but not to NS-USPIO NPs, and to a much lower level in cells exposed to equimolar concentrations of free OA. Therefore, the induction of lipid vacuoles in colon cells exposed to OA utilized as a stabilizer for USPIO NPs is higly amplified compared to free OA, and is not observed in the absence of this lipid in NS-USPIO NPs.

26/7/19, remise de décorations à la caserne des Célestins [boulevard Henri IV, 4e arrondissement] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55173

26/7/19, le colonel commandant la Garde Républicaine remet des décorations [à la caserne des Célestins, boulevard Henri IV, 4e arrondissement] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55177

Paris, 26/7/19, à la caserne des Célestins, le colonel commandant la Garde [Républicaine] décore de la Légion un chef musicien, Balay [boulevard Henri IV, 4e arrondissement] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55178

Regulation of the transforming growth factor beta-responsive transcription factor CTF-1 by calcineurin and calcium/calmodulin-dependent protein kinase IV.

Transforming growth factor beta (TGF-beta) is a pluripotent peptide hormone that regulates various cellular activities, including growth, differentiation, and extracellular matrix protein gene expression. We previously showed that TGF-beta induces the transcriptional activation domain (TAD) of CTF-1, the prototypic member of the CTF/NF-I family of transcription factors. This induction correlates with the proposed role of CTF/NF-I binding sites in collagen gene induction by TGF-beta. However, the mechanisms of TGF-beta signal transduction remain poorly understood. Here, we analyzed the role of free calcium signaling in the induction of CTF-1 transcriptional activity by TGF-beta. We found that TGF-beta stimulates calcium influx and mediates an increase of the cytoplasmic calcium concentration in NIH3T3 cells. TGF-beta induction of CTF-1 is inhibited in cells pretreated with thapsigargin, which depletes the endoplasmic reticulum calcium stores, thus further arguing for the potential relevance of calcium mobilization in TGF-beta action. Consistent with this possibility, expression of a constitutively active form of the calcium/calmodulin-dependent phosphatase calcineurin or of the calcium/calmodulin-dependent kinase IV (DeltaCaMKIV) specifically induces the CTF-1 TAD and the endogenous mouse CTF/NF-I proteins. Both calcineurin- and DeltaCaMKIV-mediated induction require the previously identified TGF-beta-responsive domain of CTF-1. The immunosuppressants cyclosporin A and FK506 abolish calcineurin-mediated induction of CTF-1 activity. However, TGF-beta still induces the CTF-1 TAD in cells treated with these compounds or in cells overexpressing both calcineurin and DeltaCaMKIV, suggesting that other calcium-sensitive enzymes might mediate TGF-beta action. These results identify CTF/NF-I as a novel calcium signaling pathway-responsive transcription factor and further suggest multiple molecular mechanisms for the induction of CTF/NF-I transcriptional activity by growth factors.