O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions

Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance. Recently isolated, glioma stem-like cells (GSCs) are thought to represent the population of tumorigenic cells responsible for GBM resistance and recurrence following surgery and chemotherapy. In addition, MGMT (O6-methylguanine-methyltransferase) methylation is considered as one of the principal mechanisms contributing to TMZ sensitivity of GBM. In this study we have isolated GSCs from 10 adult GBM patients and investigated the relationship between MGMT methylation status and Temozolomide (TMZ) sensitivity of these lines grown either in stem-like or differentiation promoting conditions. Sensitivity to TMZ was significantly associated with MGMT methylation status in cells committed to differentiation but not in stem-like cells. In addition, patients harboring highly methylated MGMT promoters had a longer overall survival. These results reveal the importance of the differentiation process when considering the predictive value of MGMT status in GSCs for clinical response to TMZ.     

Ionic nanocomposite networks in poly(styrene‐co‐methacrylic acid) copolymers with calcium carbonate

To create reversible supramolecular ionic networks, ionic cross‐links were formed from acid pendant functions in poly(styrene‐co‐methacrylic acid) copolymers by the addition of calcium carbonate. The random dispersion of acid functions in the polystyrene chain is ensured by NMR analysis. The partial reaction of the calcium carbonate with the carboxylic acids is highlighted by a limewater test. The influence of methacrylic acid and calcium‐carbonate contents on the formation of an ionic network has been studied through solubility tests. Two main effects were obtained: the exfoliation of the unreacted calcium carbonate characterized by TEM is due to ionic interactions at the surface of nanometric particles that form the first level of organization of the calcium carbonate. Another part of the calcium carbonate reacts with carboxylic acid and is detached from particles to form clusters as shown by x‐ray analysis. Finally, by analyzing the dynamic rheological spectrum, the conclusion that the strength of the ionic bonds arises with the calcium content is made. The interest of such an approach with a wide range of observed phenomena in the material is a one‐batch process to make thermoreversible nanocomposite networks. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Key Resources and Internationalization Modes of Creative Knowledge‐Intensive Business Services: The Case of Design Consultancies

In the ‘knowledge economy’, knowledge‐intensive business services (KIBS) are a key driver for innovation and competitiveness. The internationalization of these businesses raises challenges given their specificities such as knowledge intensity, the importance of customer interaction and intimacy in service delivery. This paper focuses on design consultancies as a specific type of creative KIBS for which these characteristics are emphasized. The objective of this research is to analyse the resources leveraged by the firms to compete internationally. It is based on 11 case studies of design consultancies located in five different countries (France, Italy, Portugal, Spain and the UK) that were selected for their capacity to perform at the international level for several years. The paper advances three internationalization modes depending on contingent variables and focusing on specific resources that enable international competitiveness: star‐based, process‐based and glocality‐based. In star‐based creative KIBS, the individual designer has developed a reputation that attracts customers internationally, operating as a brand. In process‐based creative KIBS, the reputation of a collective creative process attracts clients from other countries. In glocality‐based creative KIBS, the geographical proximity obtained by opening international offices helps to develop a close understanding of the client through frequent interactions, and also to know the client's market well and to better understand local codes and signs. These modes complement those presented in the existing internationalization literature which takes the peculiarities of creative KIBS into consideration.     

Changes in nutritional and sensory properties of orange juice packed in PET bottles: An experimental and modelling approach

Sensitivity to oxidation of an orange juice was investigated through packaging in standard PET or active PET with oxygen scavenger bottles. The evolution of dissolved oxygen was found to be similar in all bottles, whereas ascorbic acid degradation was related to the oxygen transfer with higher losses in standard PET (53%) against active PET (31%). Moreover, when juice was exposed to high intensity light, a fold faster degradation of ascorbic acid was observed compared to total darkness. Depending also on the light intensity and regardless of the package permeability, changes in the aromatic profile of the juice were observed due to the degradation of limonene and the formation of α-terpineol, an off-flavour. A mechanistic model was developed to predict the shelf life of orange juice. This model, coupling O₂ transfer and ascorbic acid oxidation reaction in the bottled juice, confirmed that oxygen permeation through packaging material could not be neglected.     

A novel chemometric classification for FTIR spectra of mycotoxin-contaminated maize and peanuts at regulatory limits

The rapid identification of mycotoxins such as deoxynivalenol and aflatoxin B₁ in agricultural commodities is an ongoing concern for food importers and processors. While sophisticated chromatography-based methods are well established for regulatory testing by food safety authorities, few techniques exist to provide a rapid assessment for traders. This study advances the development of a mid-infrared spectroscopic method, recording spectra with little sample preparation. Spectral data were classified using a bootstrap-aggregated (bagged) decision tree method, evaluating the protein and carbohydrate absorption regions of the spectrum. The method was able to classify 79% of 110 maize samples at the European Union regulatory limit for deoxynivalenol of 1750 µg kg^–1 and, for the first time, 77% of 92 peanut samples at 8 µg kg^–1 of aflatoxin B₁. A subset model revealed a dependency on variety and type of fungal infection. The employed CRC and SBL maize varieties could be pooled in the model with a reduction of classification accuracy from 90% to 79%. Samples infected with Fusarium verticillioides were removed, leaving samples infected with F. graminearum and F. culmorum in the dataset improving classification accuracy from 73% to 79%. A 500 µg kg^–1 classification threshold for deoxynivalenol in maize performed even better with 85% accuracy. This is assumed to be due to a larger number of samples around the threshold increasing representativity. Comparison with established principal component analysis classification, which consistently showed overlapping clusters, confirmed the superior performance of bagged decision tree classification.     

Selective Antimicrobial Therapies for Periodontitis: Win the “Battle and the War”

Traditional antimicrobial therapies for periodontitis (PD) have long focused on non-selective and direct approaches. Professional cleaning of the subgingival biofilm by instrumentation of dental root surfaces, known as scaling and root planning (SRP), is the mainstay of periodontal therapy and is indisputably effective. Non-physical approaches used as adjuncts to SRP, such as chemical and biological agents, will be the focus of this review. In this regard, traditional agents such as oral antiseptics and antibiotics, delivered either locally or systemically, were briefly reviewed as a backdrop. While generally effective in winning the “battle” against PD in the short term, by reducing its signs and symptoms, patients receiving such therapies are more susceptible to recurrence of PD. Moreover, the long-term consequences of such therapies are still in question. In particular, concern about chronic use of systemic antibiotics and their influence on the oral and gut microbiota is warranted, considering antibiotic resistance plasmids, and potential transfer between oral and non-oral microbes. In the interest of winning the “battle and the war”, new more selective and targeted antimicrobials and biologics for PD are being studied. These are principally indirect, blocking pathways involved in bacterial colonization, nutrient acquisition, inflammation or cellular invasion without directly killing the pathogens. This review will focus on current and prospective antimicrobial therapies for PD, emphasizing therapies that act indirectly on the microbiota, with clearly defined cellular and molecular targets.     

Convergences among psychoanalytic and cognitive-behavioral theories of depression.

Discusses 2 types of depression based on disruptions of (1) interpersonal relatedness or (2) self-esteem, and considers the nature, etiology, and treatment of depression based on the phenomenology of the issues that cause individuals to become depressed. The interpersonal perspective of S. Arieti and J. Bemporad (1980), the object relations perspective of J. Bowlby (see record 1988-16459-001), and the psychoanalytic ego psychology and cognitive developmental theory perspective of S. J. Blatt (1992) are compared and contrasted with each other and with the cognitive-behavioral perspective of A. T. Beck (1983). Areas of agreement and differences among these 4 theoretical positions are discussed in terms of their implications for treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Platelet-Activating Factor Quantification Using Reversed Phase Liquid Chromatography and Selected Reaction Monitoring in Negative Ion Mode

Platelet‐activating factor (PAF) is a potent biologically active phospholipid that mediates human physiological and pathophysiologic responses. PAF levels increase transiently and are typically assessed by techniques with limitations related to expense, sensitivity, pre‐analysis derivatization and interference with isobaric molecules. This study elucidates a facile, accurate liquid chromatography–mass spectrometry analytical method for PAF. In negative ion mode using electrospray ionization, collisionally‐activated dissociation analysis showed a unique product ion for acetate adducts of PAF molecular species representing the loss of methyl acetate from the polar head group and loss of a part of the acetate group from the sn‐2 position. This product ion was exploited for selected reaction monitoring of PAF molecular species following separation by reversed‐phase liquid chromatography. Standard calibration responses were determined, and this method was able to detect as low as 100 fmol of PAF. Finally, PAF molecular species were quantified in human neutrophils and monocytes.