Expression of apoptosis regulators in cutaneous malignant melanoma

Metastatic malignant melanoma (MM) is usually incurable and responds poorly to chemotherapy. Because many cytotoxic drugs cause cell death by inducing apoptosis, an imbalance of apoptosis regulatory proteins may contribute to MM treatment resistance. We have previously shown reduced expression of Bcl-2 protein, a negative regulator of apoptosis, in MM as compared with benign nevi. It is hypothesized that other apoptosis regulators may be involved in survival of MM cells. We examined the expression of Bax, Bcl-2, Bcl-X, and Mcl-1 in human benign nevi, primary MM, and metastatic MM using immunohistochemistry. Results were confirmed with Western blotting. The proapoptotic protein, Bax, was surprisingly overexpressed in all MM samples compared with benign nevi. Interestingly, in most MM samples there was overexpression of Mcl-1 or Bcl-XL, both negative regulators of apoptosis. Increased expression of Mcl-1 and Bcl-XL was first observed in thin primary melanomas, suggesting that up-regulation of these proteins represents a relatively early event associated with malignant transformation in MM. As published previously, the majority of primary and metastatic MM exhibited reduced Bcl-2 levels. We conclude that the apoptosis inhibitors Bcl-XL or Mcl-1, alone or in combination, may circumvent the normal cell death pathway, contributing to the pathogenesis and treatment resistance in metastatic MM.     

Future vaccines

Powerful genetic and immunological techniques allow the production of new vaccines. Recombinant proteins and synthetic peptides represent new categories of subunit vaccines, illustrated, respectively, by recombinant hepatitis B vaccines and a peptide-derived malaria vaccine. Virus and bacteria can be used as vectors of foreign genes encoding antigens of vaccinal interest, to build-up new forms of live vaccines. One may expect from these new strategies of vaccine production a better control of viral, bacterial and parasitic diseases and a dramatic change in vaccine recommendations for children and adults.     

REMOVAL KINETICS OF BACILLUS CEREUS SPORES FROM STAINLESS STEEL PIPES UNDER CIP PROCEDURE: INFLUENCE OF SOILING AND CLEANING CONDITIONS

Cleaning efficiency is of prime importance for food industries to ensure both the quality and safety of the products. The removal kinetics of Bacillus cereus spores adhering to unheated stainless steel pipes was studied under turbulent flow conditions (Reynolds’number of 77500 and 116300) in order to be close to those encountered in industrial practice. The experimental data was fitted using a hyperbolic tangent model. Variance analysis was then performed to underline any potential effects on the kinetics of the processing parameters, such as soiling conditions, soiling media and mean walls shear stress during cleaning. A significant influence of the adhesion medium (milk or saline) is shown at the level of spore removal (P < 0.001). This trend could probably be explained by the change in the surface properties of spores and stainless steel surfaces when covered by milk macromolecules. After milk soiling in turbulent flow conditions, removal efficiency was enhanced by a factor of 2.5 to remove 50% of the initial spore contamination and by a factor of 2 for the remaining spores after 30 min of cleaning. No effect of the two mean wall shear stresses (9.4 and 19.1 Pa) has been identified. The removal kinetic model proposed here could now permit the effect on the cleaning efficiency of a wide range of CIP conditions to be tested.     

Innovation in Complex Systems Industries: the Case of Flight Simulation

The paper proposes that the notion of complex systems usefullydescribes a group of large scale, customized products and theirassociated supply industries. Examples include flight simulators(FSs), telecommunications exchanges, military systems, airplanes,chemical process plants and heavy electrical equipment. Complexsystems, made up of many interconnected customized components,exhibit emerging properties through time as they respond tothe evolving needs of large users. Taking the FS industry asa case history, the study identifies some of the basic rulesgoverning innovation in this industry. These rules contrastsharply with those typically found in the ‘conventional’,market contest Schumpeterian model. Innovation in FS is coordinatedby an institutional structure made up of suppliers, users, regulators,industry associations and professional bodies. In contrast withco, wentional market selection, new designs are negotiated priorto product development. Long-term stability among FS makersis observed, despite radical technological discontinuities,as industrial adjustment occurs via the exit and entry of specialistsuppliers. There is no dominant design in the usual sense, nordo the conventional rules of volume competition and process-intensiveinnovation apply in FS. Competitive strategies remain focusedupon design, engineering andprototype development, rather thanincrementalprocess innovation. Collaboration occurs among theinnovation actors within institutions created by them to harnessinnovation and to allow new product markets to develop. Recognizingthe limits of a single case, the paper suggests that other complexsystems might exhibit similar processes for governing innovationand reducing risk and uncertainty in the absence of conventionalSchumpeterian market mechanisms.     

Heat Engine Drives Transport of an FeII4L4 Cage and Cargo

The directed motion of species against a chemical potential gradient is a fundamental feature of living systems, underpinning processes that range from transport through cell membranes to neurotransmission. The development of artificial active cargo transport could enable new modes of chemical purification and pumping. Here, a heat engine is described that drives chemical cargo between liquid phases to generate a concentration gradient. The heat engine, composed of a functionalized Fe^II₄L₄ coordination cage, is grafted with oligoethylene glycol imidazolium chains. These chains undergo a conformational change upon heating, causing the cage and its cargo to reversibly transfer between aqueous and organic phases. Furthermore, sectional heating and cooling allow for the cage to traverse multiple phase boundaries, allowing for longer-distance transport than would be possible using a single pair of phases.     

Spinal tuberculosis in an unusual location

OBJECTIVE: To study the effect of transforming growth factor beta 1 on tumor cells. METHOD: HL-60 cells were transfected with transforming growth factor beta 1 expression vector by electroporation. Stable cell clones resistant to G 418 were obtained after 2-3 week growth with the drug-containing medium. A series of malignant phenotype were compared between transfected and untransfected HL 60 cells. RESULTS: The growth speed of HL-60 cells which overexpressed transforming growth factor beta 1 mRNA decreased significantly. Clonigenecity in soft agarase and tumor formation in athymic mice were lower than those untransfected HL-60 cells. CONCLUSION: Suppression effect of transforming growth factor beta 1 on malignant phenotype in HL-60 cells were demonstrated.     

LASER-BASED FLOW MEASUREMENTS OF DILUTE VERTICAL PNEUMATIC TRANSPORT

Dilute vertical pneumatic transport in a vertical lifter was studied using the sophisticated measurement techniques of laser Doppler anemometry (LDA) and phase Doppler anemometry (PDA). The vertical lifter consisted of a lower fluidized silo, an upper receiving tank, and a connecting vertical transport pipe made of clear glass. The experimental study was performed in order to get detailed information of the complex gas-particle flow behavior in a dilute vertical conveying system. Particle diameter, axial particle, and tangential particle velocities, as well as root mean square velocities, were measured simultaneously for different flow conditions. In addition, overall solid mass fluxes were obtained using weighing cells. Smooth and spherical zirconium oxide (ZrO₂) solids were applied with two different particle size distributions. Measurements were performed using different flow rates of air. The air inlet condition was varied in order to study its effect on the flow behavior. The particle diameter measurements show that no axial or radial segregation by size occurs for this transport condition. The results show that the particle velocity is independent of the particle size as well. The axial velocity profiles at different heights are almost identical and flat, which indicates fully developed turbulent pipe flow. The turbulent velocity measurements show that turbulence is mainly caused by the velocity gradients, and not by particle-particle collisions in dilute flow. The solid mass flux measurements show the importance of optimum inlet condition and how this influences the mass flux.     

UPLC MS/MS Quantification of Primary Metabolites of Benzo[a]pyrene and Fluoranthene Produced In Vitro by Sole (Solea solea) Liver Microsomal Activation

Biotransformation pathways of PAHs in a flat fish, Solea solea, living in nurseries close to coastal areas and estuaries constitute a great challenge for the environmental risk. Among PAHs, Fluoranthene (Fluo) has a different chemical structure than benzo[a]pyrene (BaP), and can influence its biotransformation pathways and genotoxic potential. The aim of this study was to bring some response elements about the in vitro metabolic activation of Fluo and BaP by sole liver microsomes. The quantification of several primary metabolites of BaP and Fluo produced in vitro, following a sole liver microsomal activation, was conducted using a sensitive analytical UPLC MS/MS method.

Four types of BaP metabolites (dihydrodiols, diones, OH-BaP, and 7,8-dihydro-epoxide), and three types of Fluo metabolites (2,3-dihydrodiol, 2,3-dione, and sum of OH-Fluo) were quantified. The concentration for which the metabolite production was maximal was of 40 μM and 100 μM for BaP and Fluo, respectively. The biotransformation rate was higher for Fluo (9.97%) than for BaP (6.69%).Whatever the PAH, dihydrodiols and phenols were the major metabolites produced accounting for, respectively, 50% and 30–40% for BaP, and 40 and 60% for Fluo. Despite some differences in conformation, both PAHs seem to be activated by similar pathways and the diol-epoxide appears as a predominant one.     

Are 1,4‐ and 1,5‐Disubstituted 1,2,3‐Triazoles Good Pharmacophoric Groups?

Over the last decade, 1,2,3‐triazoles have received increasing attention in medicinal chemistry thanks to the discovery of the highly useful and widely applicable 1,3‐dipolar cycloaddition reaction between azides and alkynes (click chemistry) catalyzed by copper salts and ruthenium complexes. After a decade of medicinal chemistry research on 1,2,3‐triazoles, we feel that the time is ripe to demonstrate the real ability of this heterocycle to participate in important and pivotal binding interactions with biological targets while maintaining a good pharmacokinetic profile. In this study, we retrieved and analyzed X‐ray crystal structures of complexes between 1,2,3‐triazoles and either proteins or DNA to understand the pharmacophoric role of the triazole. Furthermore, the metabolic stability, the capacity to inhibit cytochromes, and the contribution of 1,2,3‐triazoles to the overall aqueous solubility of compounds containing them have been analyzed. This information should furnish fresh insight for medicinal chemists in the design of novel bioactive molecules that contain the triazole nucleus.