Evaluation of biological activities of Physalis peruviana ethanol extracts and expression of Bcl-2 genes in HeLa cells

Physalis species are used in folk medicine for phytotherapeutic properties. The extracts of medicinal plants are known to possess cytotoxic and chemopreventative compounds. In this study we investigated antibacterial, antioxidant, DNA damage preventative properties of Physalis peruviana (golden berry) on leaf and shoot ethanol extracts and their effects on cytotoxicity of HeLa cells and expression of apoptotic pathway genes. Among the tested bacteria for antibacterial activity, maximum inhibition zone was determined in Lactococcus lactis. The phenolic content was found higher in leaf extracts than shoot extracts. The antioxidant activity showed the highest TEAC values of the leaf (2 mg/mL) and the shoot (0.5 mg/mL) extracts as 0.291±0.04 and 0.192±0.015, respectively. In DNA damage prevention assay both leaf and shoot extracts, especially 30 and 20 µg/mL concentrations, exhibited significant protection against DNA damage-induced by hydroxyl radical generated by Fenton reaction. Our results suggest that leaf and shoot extracts possess cytotoxic effect on HeLa cells when applied as 100 µg/mL concentration. Also mRNA expression analysis showed the alteration of antiapoptotic genes, so the results suggest that P. peruviana ethanol extracts induce apoptotic cell death and should be investigated for identification of active compounds and their mechanisms of action.

Herbert A. Simon and the concept of rationality: boundaries and procedures

This paper discusses Herbert A. Simon's conception of rationality in two of its principal general definitions: bounded rationality and procedural rationality. It argues that the latter is the one that better synthesizes the author's view about rational behavior and that the former fills mainly a critical function. They are complementarily used by Simon in this sense. In spite of that, it is argued that it is the low degree of specificity of the concept of bounded rationality one of the reasons for its relatively greater success.

The concept of emerging power in international politics and economy

ABSTRACT This paper aims to analyze the concept of emerging power established to the understanding of international affairs. The work observes that the use of the lexicon emerging - regarding to markets, countries or powers - as qualifier for a range of international relations phenomena became a constituent part of the matter. In spite of that, the empirical denotation of the predicate is ahead of the amount of efforts on its theoretical contextualization. Our methodological hypothesis is that the rational denial of the concepts prevailing connotative spectrum by acknowledging the embedded wisdom about cognate phenomena synthesizes a theoretical framework on its accurate use.

Marginal/minority popular music : the concept of the "third space" and the case for "hybridities" of cultures/identities /

The topic of this thesis is marginaVminority popular music and the question of identity; the term "marginaVminority" specifically refers to members of racial and cultural minorities who are socially and politically marginalized. The thesis argument is that popular music produced by members of cultural and racial minorities establishes cultural identity and resists racist discourse. Three marginaVminority popular music artists and their songs have been chosen for analysis in support of the argument: Gil Scott-Heron's "Gun," Tracy Chapman's "Fast Car" and Robbie Robertson's "Sacrifice." The thesis will draw from two fields of study; popular music and postcolonialism. Within the area of popular music, Theodor Adorno's "Standardization" theory is the focus. Within the area of postcolonialism, this thesis concentrates on two specific topics; 1) Stuart Hall's and Homi Bhabha's overlapping perspectives that identity is a process of cultural signification, and 2) Homi Bhabha's concept of the "Third Space." For Bhabha (1995a), the Third Space defines cultures in the moment of their use, at the moment of their exchange. The idea of identities arising out of cultural struggle suggests that identity is a process as opposed to a fixed center, an enclosed totality. Cultures arise from historical memory and memory has no center. Historical memory is de-centered and thus cultures are also de-centered, they are not enclosed totalities. This is what Bhabha means by "hybridity" of culture - that cultures are not unitary totalities, they are ways of knowing and speaking about a reality that is in constant flux. In this regard, the language of "Otherness" depends on suppressing or marginalizing the productive capacity of culture in the act of enunciation. The Third Space represents a strategy of enunciation that disrupts, interrupts and dislocates the dominant discursive construction of US and THEM, (a construction explained by Hall's concept of binary oppositions, detailed in Chapter 2). Bhabha uses the term "enunciation" as a linguistic metaphor for how cultural differences are articulated through discourse and thus how differences are discursively produced. Like Hall, Bhabha views culture as a process of understanding and of signification because Bhabha sees traditional cultures' struggle against colonizing cultures as transforming them. Adorno's theory of Standardization will be understood as a theoretical position of Western authority. The thesis will argue that Adorno's theory rests on the assumption that there is an "essence" to music, an essence that Adorno rationalizes as structure/form. The thesis will demonstrate that constructing music as possessing an essence is connected to ideology and power and in this regard, Adorno's Standardization theory is a discourse of White Western power. It will be argued that "essentialism" is at the root of Western "rationalization" of music, and that the definition of what constitutes music is an extension of Western racist "discourses" of the Other. The methodological framework of the thesis entails a) applying semiotics to each of the three songs examined and b) also applying Bhabha's model of the Third Space to each of the songs. In this thesis, semiotics specifically refers to Stuart Hall's retheorized semiotics, which recognizes the dual function of semiotics in the analysis of marginal racial/cultural identities, i.e., simultaneously represent embedded racial/cultural stereotypes, and the marginal raciaVcultural first person voice that disavows and thus reinscribes stereotyped identities. (Here, and throughout this thesis, "first person voice" is used not to denote the voice of the songwriter, but rather the collective voice of a marginal racial/cultural group). This dual function fits with Hall's and Bhabha's idea that cultural identity emerges out of cultural antagonism, cultural struggle. Bhabha's Third Space is also applied to each of the songs to show that cultural "struggle" between colonizers and colonized produces cultural hybridities, musically expressed as fusions of styles/sounds. The purpose of combining semiotics and postcolonialism in the three songs to be analyzed is to show that marginal popular music, produced by members of cultural and racial minorities, establishes cultural identity and resists racist discourse by overwriting identities of racial/cultural stereotypes with identities shaped by the first person voice enunciated in the Third Space, to produce identities of cultural hybridities. Semiotic codes of embedded "Black" and "Indian" stereotypes in each song's musical and lyrical text will be read and shown to be overwritten by the semiotic codes of the first person voice, which are decoded with the aid of postcolonial concepts such as "ambivalence," "hybridity" and "enunciation."

Experiential learning instruments : an examination of the concept of the instrumental approach in experiential learning

Experiential Learning Instruments (ELls) are employed to modify the leamer's apprehension and / or comprehension in experiential learning situations, thereby improving the efficiency and effectiveness of those modalities in the learning process. They involve the learner in reciprocally interactive and determining transactions with his/her environment. Experiential Learning Instruments are used to keep experiential learning a process rather than an object. Their use is aimed at the continual refinement of the learner's knowledge and skill. Learning happens as the leamer's awareness, directed by the use of Ells, comes to experience, monitor and then use experiential feedback from living situations in a way that facilitates knmvledge/skill acquisition, self-correction and refinement. The thesis examined the literature relevant to the establishing of a theoretical experiential learning framework within which ELls can be understood. This framework included the concept that some learnings have intrinsic value-knowledge of necessary information-while others have instrumental value-knowledge of how to learn. The Kolb Learning Cycle and Kolb's six characteristics of experiential learning were used in analyzing three ELls from different fields of learning-saxophone tone production, body building and interpersonal communications. The ELls were examined to determine their learning objectives and how they work using experiential learning situations. It was noted that ELls do not transmit information but assist the learner in attending to and comprehending aspects of personal experience. Their function is to telescope the experiential learning process.

The effect of literacy training on the self-concept of moderately mentally handicapped adults

In this single group, pretest/posttest design study the literacy level and self-concept of nine moderately mentally handicapped adults was assessed. The participants in the study were involved in reading lessons using the Ball-Stick-Bird reading system, a brainbased program. No significant differences were found in either literacy level or reading level after intervention. However, there were changes in reading behaviour. These changes occurred in the subskills ofdirectionality, letter-sound correspondence, wordreading, and use of reading materials.

Outline of the evolution of the Falls of Niagara, contrast with the Falls of Zambesi /

At head of title: For the International Geological Congress.

Role of the protein tyrosine phosphatase DEP-1 in Src activation and the mediation of biological cell functions of endothelial and breast cancer cells

L’implication des protéines tyrosines phosphatases (PTPs) dans la régulation de la signalisation et la médiation des fonctions cellulaires a été bien établie dans les dernières années. Cependant, les mécanismes moléculaires par lesquels les PTPs régulent les processus fondamentaux tels que l’angiogenèse demeurent méconnus. Il a été rapporté que l’expression de la PTP DEP-1 (Density-enhanced phosphatase 1) augmente avec la densité cellulaire et corrèle avec la déphosphorylation du récepteur VEGFR2. Cette déphosphorylation contribue à l’inhibition de contact dans les cellules endothéliales à confluence et diminue l’activité du VEGFR2 en déphosphorylant spécifiquement ses résidus catalytiques Y1054/1059. De plus, la plupart des voies de signalisation en aval du VEGFR2 sont diminuées sauf la voie Src-Gab1-AKT. DEP-1 déphosphoryle la Y529 de Src et contribue à la promotion de la survie dans les cellules endothéliales. L’objectif de cette thèse est de mieux définir le rôle de DEP-1 dans la régulation de l’activité de Src et les réponses biologiques dans les cellules endothéliales. Nous avons identifié les résidus Y1311 et Y1320 dans la queue C-terminale de DEP-1 comme sites majeurs de phosphorylation en réponse au VEGF. La phosphorylation de ces résidus est requise pour l’activation de Src et médie le remodelage des jonctions cellules-cellules dépendantes de Src. Ce remodelage induit la perméabilité, l’invasion et la formation de capillaires en réponse au VEGF. Nos résultats démontrent que la phosphorylation de DEP-1 sur résidu tyrosine est requise pour diriger la spécificité de DEP-1 vers son substrat Src. Les travaux révèlent pour la première fois un rôle positif de DEP-1 sur l’induction du programme angiogénique des cellules endothéliales. En plus de la phosphorylation sur tyrosine, DEP-1 est constitutivement phosphorylé sur la thréonine 1318 situé à proximité de la Y1320 en C-terminal. Cette localisation de la T1318 suggère que ce résidu pourrait être impliqué dans la régulation de la Y1320. En effet, nous avons observé que la T1318 de DEP-1 est phosphorylée potentiellement par CK2, et que cette phosphorylation régule la phosphorylation de DEP-1 sur tyrosine et sa capacité de lier et d’activer Src. En accord avec ces résultats, nos travaux révèlent que la surexpression du mutant DEP-1 T1318A diminue le remodelage des jonctions cellules-cellules et par conséquent la perméabilité. Nos résultats suggèrent donc que la T1318 de DEP-1 constitue un nouveau mécanisme de contrôle de la phosphorylation sur tyrosine et que ceci résulte en l’activation de Src et l’induction des fonctions biologiques des cellules endothéliales en réponse au VEGF. Suite à ces travaux dans les cellules endothéliales qui démontrent un rôle positif de DEP-1 dans la médiation des réponses angiogéniques, nous avons voulu approfondir nos connaissances sur l’implication potentielle de DEP-1 dans les cellules cancéreuses où l’activité de Src est requise pour la progression tumorale. Malgré le rôle connu de DEP-1 comme suppresseur tumoral dans différents types de cancer, nous avons émis l’hypothèse que DEP-1 pourrait promouvoir les fonctions biologiques dépendantes de Src telles que la migration et l’invasion dans les cellules cancéreuses. Ainsi, nous avons observé que l’expression de DEP-1 est plus élevée dans les lignées basales de cancer du sein qui sont plus invasives comparativement aux lignées luminales peu invasives. Dans les lignées basales, DEP-1 active Src, médie la motilité cellulaire dépendante de Src et régule la localisation des protéines impliquées dans l’organisation du cytosquelette. L’analyse d’un micro-étalage de tissu a révélé que l’expression de DEP-1 est associée avec une réduction tendencielle de survie des patients. Nos résultats proposent donc, un rôle de promoteur tumoral pour DEP-1 dans la progression du cancer du sein. Les travaux présentés dans cette thèse démontrent pour la première fois que DEP-1 peut agir comme promoteur des réponses angiogéniques et du phénotype pro-invasif des lignées basales du cancer du sein probablement du à sa capacité d’activer Src. Nos résultats suggèrent ainsi que l’expression de DEP-1 pourrait contribuer à la progression tumorale et la formation de métastases. Ces découvertes laissent donc entrevoir que DEP-1 représente une nouvelle cible thérapeutique potentielle pour contrer l’angiogenèse et le développement du cancer.

Reconsidering the concept of ‘dual-use’ in the context of neuroscience research

Commentaire / Commentary

Drug-loaded nanocarriers : passive targeting and crossing of biological barriers

Poor bioavailability and poor pharmacokinetic characteristics are some of the leading causes of drug development failure. Therefore, poorly-soluble drugs, fragile proteins or nucleic acid products may benefit from their encapsulation in nanosized vehicles, providing enhanced solubilisation, protection against degradation, and increased access to pathological compartments. A key element for the success of drug-loaded nanocarriers (NC) is their ability to either cross biological barriers themselves or allow loaded drugs to traverse them to achieve optimal pharmacological action at pathological sites. Depending on the mode of administration, NC may have to cross different physiological barriers in their journey towards their target. In this review, the crossing of biological barriers by passive targeting strategies will be presented for intravenous delivery (vascular endothelial lining, particularly for tumour vasculature and blood-brain barrier targeting), oral administration (gastrointestinal lining) and upper airway administration (pulmonary epithelium). For each specific barrier, background information will be provided on the structure and biology of the tissues involved as well as available pathways for nano-objects or loaded drugs (diffusion and convection through fenestration, transcytosis, tight junction crossing, etc.). The determinants of passive targeting − size, shape, surface chemistry, surface patterning of nanovectors − will be discussed in light of current results. Perspectives on each mode of administration will be presented. The focus will be on polymeric nanoparticles and dendrimers although advances in liposome technology will be also reported as they represent the largest body in the drug delivery literature.

Biochemical Investigations on the Stability of Biological Membranes

In this project, an attempt has been made to study the stability of erythrocyte and lysosomal membranes biochemically. Erythrocytes were chosen for the study because of their ready availability and relative simplicity. Biological membranes forming closed boundaries between compartments of varying composition consist mainly of proteins and lipids. They are asymmetric, fluid structures that are thermodynamically stable and metabolically active. Normal cellular function begins with normal membrane structure and any variation in it may upset the normal functions. The degree of fluidity of a membrane depends on the chain length of its lipids and degree of unsaturation of constituent fatty acids. In response to environmental changes, many cells can regulate composition of their membranes to maintain the overall semi fluid environment necessary for many membrane associated functions. The assembly and Maintenance of membrane structures in cells is a dynamic process. The components are not only synthesized and inserted into a growing membrane but are also continuously degraded at a slower rate. This turnover process varies with each individual molecule.Lysosomes are important in the catabolic processes occurring in the cell. Lysosomes contain hydrolytic enzymes and are stable under normal conditions. In certain pathological conditions, the lysosomal membrane may rupture, releasing the hydrolytic enzymes into the cell and digestion of cell takes place as a whole. This is very dangerous. In normal life processes of multi cellular organisms, lysosomes rupture following the death of a cell and it may have some value as a built in mechanism for selfremoval of dead cells.An attempt has also been made in this project towards developing lysosome membrane stability as an index of fish spoilage during storage. Different membranes within the cell and between cells have different compositions as reflected in the ratio of protein to lipid. The difference is not surprising given the very different functions of membranes