In vivo stress preconditioning

The heat shock or stress protein response is a highly conserved defense mechanism. Activation of the stress protein response by mild hyperthermia or by pharmacological agents allows cells to withstand a subsequent metabolic insult that would otherwise be lethal, a phenomenon referred as "thermotolerance" or "preconditioning." Heat shock response is characterized by increased expression of stress proteins that provide cellular protection, e.g., via increased chaperoning activity in all organisms, from bacteria to animals and humans. Indeed, there is experimental evidence that overexpression of specific heat shock proteins or heat shock factors produce protective effects similar to those observed after stress preconditioning. The purpose of this review is first to discuss the methods used to induce in vivo thermotolerance with mild hyperthermia or pharmacological agents. Then, as an example of the organ protection provided by in vivo stress preconditioning, the second part of this paper will examine how the induction of thermotolerance modulates the lung inflammatory response associated with acute lung injury, thus providing broad organ and tissue protection against oxidative stress associated this syndrome.     

Stress-induced inhibition of the NF-kappaB signaling pathway results from the insolubilization of the IkappaB kinase complex following its dissociation from heat shock protein 90

Activation of the stress response attenuates proinflammatory responses by suppressing cytokine-stimulated activation of the NF-kappaB signaling pathway. In this study, we show that the activation of the cellular stress response, either by heat shock treatment or after exposure to sodium arsenite, leads to a transient inhibition of IkappaBalpha phosphorylation. Inhibition of IkappaBalpha phosphorylation after stress was associated with the detergent insolubilization of the upstream kinases, IkappaB kinase alpha (IKKalpha) and IkappaB kinase beta, components involved in IkappaBalpha phosphorylation. Pretreatment of cells with glycerol, a chemical chaperone that reduces the extent of stress-induced protein denaturation, reduced the stress-dependent detergent insolubility of the IKK complex and restored the cytokine-stimulated phosphorylation of IkappaB. The stress-dependent insolubility of the IKK complex appeared reversible; as the cells recovered from the heat shock treatment, the IKK complex reappeared within the soluble fraction of cells and was again capable of mediating the phosphorylation of IkappaBalpha in response to added cytokines. Treatment of cells with geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) function, also resulted in IKK detergent insolubility and proteasome-mediated degradation of the IKK complex. Furthermore, while IKKalpha coprecipitated with Hsp90 in control cells, coprecipitation of the two proteins was greatly reduced in those cells early after stress or following exposure to geldanamycin. Stress-induced transient insolubilization of the IkappaB kinase complex following its dissociation from Hsp90 represents a novel mechanism by which the activation of the stress response inhibits the NF-kappaB signaling pathway in response to proinflammatory stimuli.     

Alpha 3 domain mutants of peptide/MHC class I multimers allow the selective isolation of high avidity tumor-reactive CD8 T cells

The goal of adoptive T cell therapy in cancer is to provide effective antitumor immunity by transfer of selected populations of tumor Ag-specific T cells. Transfer of T cells with high TCR avidity is critical for in vivo efficacy. In this study, we demonstrate that fluorescent peptide/MHC class I multimeric complexes incorporating mutations in the alpha3 domain (D227K/T228A) that abrogate binding to the CD8 coreceptor can be used to selectively isolate tumor Ag-specific T cells of high functional avidity from both in vitro expanded and ex vivo T cell populations. Sorting, cloning, and expansion of alpha3 domain mutant multimer-positive CD8 T cells enabled rapid selection of high avidity tumor-reactive T cell clones. Our results are relevant for ex vivo identification and isolation of T cells with potent antitumor activity for adoptive T cell therapy.     

Human thymus exports naive CD8 T cells that can home to nonlymphoid tissues

Functionally naive CD8 T cells in peripheral blood from adult humans can be fully described by their CD45RA(bright)CCR7(+)CD62L(+) cell surface phenotype. Cord blood lymphocytes, from healthy newborns, are homogenously functionally naive. Accordingly, the majority of cord blood CD8 T cells express the same pattern of cell surface molecules. Unexpectedly, however, a significant fraction of cord blood CD8 T cells express neither CCR7 nor CD62L. Yet these cells remain functionally naive as they contain high levels of TCR excision circles, have long telomeres, display highly polyclonal TCRs, and do not exhibit immediate effector functions. In addition, these CD8 T cells already represent a significant fraction of the mature naive CD8 single-positive thymocyte repertoire and may selectively express the cutaneous lymphocyte Ag. We suggest that CD8 single-positive thymocytes comprise two pools of naive precursors that exhibit distinct homing properties. Once seeded in the periphery, naive CCR7(+)CD62L(+) CD8 T cells patrol secondary lymphoid organs, whereas naive CCR7(-)CD62L(-) CD8 T cells selectively migrate to peripheral tissues such as skin.     

Reactive nitrogen species inhibit alveolar epithelial fluid transport after hemorrhagic shock in rats

Our recent experimental work demonstrated that a neutrophil-dependent inflammatory response in the lung prevented the normal up-regulation of alveolar fluid clearance by catecholamines following hemorrhagic shock. In this study, we tested the hypothesis that the release of NO within the airspaces of the lung was responsible for the shock-mediated failure of the alveolar epithelium to respond to catecholamines in rats. Hemorrhagic shock was associated with an inducible NO synthase (iNOS)-dependent increase in the lung production of NO and a failure of the alveolar epithelium to up-regulate vectorial fluid transport in response to beta-adrenergic agonists. Inhibition of iNOS restored the normal catecholamine-mediated up-regulation of alveolar liquid clearance. Airspace instillation of dibutyryl cAMP, a stable analog of cAMP, restored the normal fluid transport capacity of the alveolar epithelium after prolonged hemorrhagic shock, whereas direct stimulation of adenyl cyclase by forskolin had no effect. Pretreatment with pyrrolidine dithiocarbamate or sulfasalazine attenuated the iNOS-dependent production of NO in the lung and restored the normal up-regulation of alveolar fluid clearance by catecholamines after prolonged hemorrhagic shock. Based on in vitro studies with an alveolar epithelial cell line, A549 cells, the effect of sulfasalazine appeared to be mediated in part by inhibition of NF-kappaB activation, and the protective effect was mediated by the inhibition of IkappaBalpha protein degradation. In summary, these results provide the first in vivo evidence that NO, released within the airspaces of the lung probably secondary to the NF-kappaB-dependent activation of iNOS, is a major proximal inflammatory mediator that limits the rate of alveolar epithelial transport after prolonged hemorrhagic shock by directly impairing the function of membrane proteins involved in the beta-adrenergic receptor-cAMP signaling pathway in alveolar epithelium.     

Cutting edge: cytolytic effector function in human circulating CD8+ T cells closely correlates with CD56 surface expression

Recent data suggest that human effector CD8+ T cells express a distinct CD27-CD45RAhigh (CD57+CD28-CD11ahigh) phenotype. Here, we propose that CTL effector function correlates better with CD56 (neuronal cell adhesion molecule (NCAM)) surface expression. CD56 was absent on cord blood CD8+ T cells, but was expressed by 4-30% of freshly isolated circulating CD8+ T cells from 15 adults. Dramatic oligoclonal expansions in 3/3 individuals were confined to the CD56+ subset of CD8+ T cells. The CD56+ subset generally contained high amounts of intracellular perforin and granzyme B. Finally, direct cytolytic capacity was closely restricted to the CD56+(CD45RAhigh) cells, better than to CD27-CD45RAhigh cells in 5/5 individuals analyzed. Thus, the phenotype corresponding to the circulating effector CD8+ T cell pool may be simplified and more precisely defined by the use of just two surface markers: CD8 and CD56.     

Facies analysis and depositional environments of the Taulanne Limestone Formation in the South Alpine Foreland Basin (Oligocene, southeastern of France)

The Taulanne Limestone Formation of the Castellane region (South Alpine Foreland Basin of France) represents an Oligocene lake depositional system developed above the marine Nummulitic succession. A sedimentological analysis of the Taulanne limestone allows the identification of nine marine, lacustrine, and palustrine facies. The spatial and temporal distribution of these facies records five depositional sequences that are correlated between the Sant Peire section (edge of the lake) and the Prés section (central lake). Water-level variations highlight the high-frequency balance between drying and wetting periods under fluctuating climatic conditions. Lacustrine facies developed during more humid periods while palustrine facies correspond to more arid conditions and longer lake shoreline exposure. At the basin scale, the lateral changes in accommodation space are attributed to differential subsidence between the Prés and the Sant Peire sections, which permitted the deposition of a thicker succession in the central part of the lake (Prés section). The Taulanne limestone records a marine to continental transition. The progressive filling of the basin is related to the regional tectonic activity, namely the emplacement of the Embrun-Ubaye nappes to the northeast of the study area at about 30–32 Ma. This final regressive trend represents the transition between the underfilled flysch stage (marine Nummulitic succession) of a foreland-basin cycle to the overfilled stage (alluvial Red Molasse deposits) during the primary exhumation of the Internal Alps.     

Note Sui Grani a Spighe Ramificate

Resumé

Chez les Blés branchus de l'espèce «turgidum» (Triticum turgidum compositum), il existe des sortes à thermostade plutôt froid (Blés d'hiver ou de semi-hiver) et des sortes à thermostade chaud, tièe ou «indifférent» (Blés de printemps).

Les Blés branchus de l'espèce «turgidum» apparaissent comme étant des plantes à photostade de jour long.

La plus ou moins grande rapidité de l'accomplissement du photostade, par rapport à la rapidité de l'assimilation des matières plastiques, détermine la structure, — non ramifiée ou ramifiée — de l'épi.