Shaping of an effective immune microenvironment to and by cancer cells

A high density of intratumoral effector memory CD8+/Th1 T cells is associated with favorable prognosis in most cancers and may be induced or increased by immunotherapy. Efficient adaptive immune reactions are shaped in tumor adjacent tertiary lymphoid structures, which exhibit all characteristics of immunity generating lymphoid formations in reactive lymph nodes. Malignant tumor cells impact favorably or deleteriously their immune microenvironment if they bear genetic mutations that result in neo-antigens or by producing chemokines and cytokines that recruit lymphocytes and myeloid cells or increase inflammation and neo-angiogenesis. This intricate network of interactions results in control or escape of tumors, and its understanding will help define goals to monitor efficiency of immunotherapies.     

Life Cycle Assessment of Water: From the pumping station to the wastewater treatment plant (9 pp)

Goal, Scope and Background The goal of this study is to determine the environmental impact of using one cubic metre of water in the Walloon Region. The whole anthropogenic water cycle is analysed, from the pumping stations to the wastewater treatment plants. The functional unit has been defined as one cubic metre of water at the consumer tap. This study was carried out in the context of the EU Water Framework Directive. It is part of a programme called PIRENE launched by the Walloon Region to fulfil the requirements of this Directive. Methods A model of the whole anthropogenic water cycle in the Walloon Region was developed. The model is mainly based on site-specific data given by the companies working in the field of water production and wastewater treatment. It was used to assess the environmental impact from the pumping station to the wastewater treatment plant using the Eco-Indicator 99 methodology. Eco-Indicator 99 has been adapted in order to better take into account environmental impact of acidification and eutrophication. Characterisation factors have been calculated for COD, nitrogen and phosphate emissions. From the reference model, different scenarios have been elaborated. Results and Discussion On the basis of the inventory, the environmental impact of five scenarios has been evaluated. Acidification and eutrophication is the most important impact category. It is mainly caused by the wastewater that is discharged without any treatment, but also by the effluent of the wastewater treatment plant. So, this impact category has the lowest environmental load when the wastewater treatment rate is high. For the other impact categories, the impact generally increases with the wastewater treatment rate. During wastewater treatment, energy and chemicals are indeed consumed to improve the quality of the final outputs, and thus to reduce the environmental impact related to acidification and eutrophication. A comparison between the scenarios has also shown that the building of the sewer network has a significant contribution to the global environmental load and that the stages before the tap contribute less to the environmental impact than the stage after the tap. Conclusions The three stages that contribute significantly to the global environmental load are: water discharge, wastewater treatment operation and, to a lesser extent, the sewer system. The results show that the wastewater treatment rate must be as high as possible, using either collective or individual wastewater treatment plants. Even a small water discharge without any treatment has a significant environmental impact. Operation of the wastewater treatment plants must also be improved to reduce the environmental impact caused by the effluent of the plants. For new wastewater treatment plants, building plants treating nitrogen and phosphorus should be encouraged. A sensitivity analysis was conducted and showed that the results of the study were not very affected by a modification of key parameters. Impact assessment using the CML methodology has confirmed the results obtained with Eco-Indicator 99.     

Assessment of upper airway stabilizing forces with the use of phrenic nerve stimulation in conscious humans.

Phrenic nerve stimulation (PNS) applied at end-expiration allows the investigation of passive upper airway (UA) dynamic during wakefulness. Assuming that phasic UA dilating/stabilizing forces should modify the UA properties when twitches are applied during inspiration, we compared the UA dynamic responses to expiratory and inspiratory twitches (2 s and 200 ms after expiratory and inspiratory onset, respectively) in nine men (mean age 28 yr). This procedure was repeated with a 2-cm mouth opening provided with a closed mouthpiece. The percentage of flow-limited (FL) twitches was significantly higher when PNS was realized during expiration than during inspiration. Maximal inspiratory flow (Vi(max)) of FL twitches was significantly higher for inspiratory twitches (1,383 +/- 42 and 1,185 +/- 40 ml/s). With mouth aperture, Vi(max) decreased with an increase in the corresponding pharyngeal resistance values, and the percentage of twitch with a FL regimen increased but only for inspiratory twitches. We conclude that 1) UA dynamics are significantly influenced by the inspiratory/expiratory timing at which PNS is applied, 2) the improvement in UA dynamic properties observed from expiratory to inspiratory PNS characterizes the overall inspiratory stabilizing effects, and 3) mouth aperture alters the stability of UA structures during inspiration.     

Exogenous abscisic acid fate during maturation of hybrid larch (Larix×leptoeuropaea) somatic embryos

The maturation of somatic embryogenesis of hybrid larch is an essential step for plantlet production. ABA controls not only synchronicity of maturation, but has important consequences on eventual viability of the plantlet. To gain understanding of the role of this plant growth regulator during the maturation process of hybrid larch somatic embryos, we studied the incorporation of [ 3 H]-(±)-abscisic acid [tritiated (±)-ABA] over 6 weeks of culture. Results showed a rapid incorporation of label into the tissues directly in contact with the culture medium. Accumulation of tritiated (±)-ABA occurred mainly in the maturing somatic embryos found at the periphery of the embryogenic mass but not in direct contact with the culture medium. Tritiated (±)-ABA was mainly conjugated as a glucose ester form. Rates of tritium incorporation indicated a significant build-up in tritiated (±)-ABA metabolization at the third week of culture. The weekly measurement of labelling in the culture medium over 6 weeks showed no localized exhaustion of tritiated (±)-ABA in positions where the embryogenic masses were placed in Petri dishes. The calculated ABA internal content of the maturing somatic embryos was similar to published ELISA measurements of ABA. This result suggests an absence of endogenous ABA synthesis by somatic embryos of hybrid larch during maturation.     

Stable acid phosphatase: I. Demonstration and distribution

Summary After a pH-dependent reactivation a highly stable form of acid phosphatase (SAPhase) could be demonstrated in active cells of the macrophage/giant cell/osteoclast series and also in epiphyseal chondrocytes, in cells lining bone undergoing resorption and in hamster cosinophils. Because acid phosphatases of epithelial cells in rat, hamster and Macaca sp. tissues did not possess this stability, SAPhase served as a useful cell marker for the above mesenchymal cell types in paraffin and glycol-methacrylate sections even after rapid demineralization in acidic buffers. Conformational alterations appear to occur in the enzyme during formaldehyde fixation, embedding, and reactivation. The granular staining of SAPhase and the successful use of a non-aqueous fixative suggest an association of SAPhase with lysosomes and their membranes. Cells of mesenchymal origin that are actively engaged in intra- and/or extracellular digestion contain high levels of SAPhase. The distribution and properties of SAPhase indicate an interrelationship between mononuclear and mutinuclear cell types actively engaged in such digestive processes.Supported by the Medical Research Council of Great Britain     

Human succinate dehydrogenase: Biochemical and genetic characterization

A simple procedure for the preparation of soluble human succinate dehydrogenase is described. These preparations have proved suitable for analysis by zone electrophoresis, using a specific stain to detect activity after separation. In a survey of succinate dehydrogenase from various tissues and different individuals, no evidence for genetic heterogeneity due to the expression of either multiple loci or alternative alleles at the succinate dehydrogenase locus was found. However, epigenetic heterogeneity in both molecular size and charge was seen and various explanations for the occurrence of the isoenzymes are explored. Estimates of molecular size (93,300 ± 9100) suggest that the smallest active unit of succinate dehydrogenase accounts for the major part of the solubilized activity. Kinetic studies have shown that the apparent K _m values for succinate (0.9mm) and PMS (0.4mm) are comparable to those previously described for the beef heart enzyme, and these parameters were not significantly altered when the enzyme was removed from the membrane milieu. However a marked non-succinate-dependent activation of the membrane-associated enzyme at 38C is apparently lost on solubilization, and this observation may have some bearing on earlier reports of an apparent decrease in V _max on solubilization of succinate dehydrogenase.