Pramanicin-a induces apoptosis in hct116 colon carcinoma cells: activation of jnk, p38, erk1/2 and induction of oxidative stress

Pramanicin (PMC) is a novel anti-fungal agent. In this study, among eight analogues screened by MTT cell proliferation assay for their potential cytotoxic effect on HCT116 colon cancer cells, Pramanicin-A and Pramanicin-F were found to be the most effective candidates at the concentration of 25uM and 75uM respectively. Flow-cytometric analyses with Annexin-V staining and M30 apoptosense eliza assay confirmed that PMC-A is a more effective apoptotic agent compared to PMC-F, thus PMC-A was selected for further studies. Moreover, no difference in cytotoxicity was observerved in puma and bax defficient cell lines, therefore further studies were conducted with HCT116 wild type cells. In order to get insight into the mechanism of apoptotic response by PMC-A, we followed MAP kinase pathways with using specific MAPK antibodies and inhibitors. Our immunoblotting data reveals that PMC-A induced the activation/phosphorilation of c-jun terminal kinase (JNK), p38 and extracellular signal-regulated kinases (ERK1/2) in different time kinetics. Inhibition of caspase-3, and caspase-9 with their specific inhibitors prevent apoptosis. Interestingly inhibition of JNK and p38 activations/phosphorilations potentiated the apoptotic response. These data indicate that PMC-A induced apoptosis is mediated by caspase dependent pathways, activation of JNK and p38 but not ERK 1/2 may have a pro-survival role.Finally our data from flow-cytometric and flourometric analyses with D2CDF-DA staining revealed induction of reactive oxygen species (ROS) acting as second messengers which may activate MAPK signaling pathways as well as other signaling pathways in apoptotic response of cells to PMC-A at early (1h, 2h) and late (24h) time points

Oxidative stress is a mediator for increased lipid accumulation in a newly isolated Dunaliella salina strain

Green algae offer sustainable, clean and eco-friendly energy resource. However, production efficiency needs to be improved. Increasing cellular lipid levels by nitrogen depletion is one of the most studied strategies. Despite this, the underlying physiological and biochemical mechanisms of this response have not been well defined. Algae species adapted to hypersaline conditions can be cultivated in salty waters which are not useful for agriculture or consumption. Due to their inherent extreme cultivation conditions, use of hypersaline algae species is better suited for avoiding culture contamination issues. In this study, we identified a new halophilic Dunaliella salina strain by using 18S ribosomal RNA gene sequencing. We found that growth and biomass productivities of this strain were directly related to nitrogen levels, as the highest biomass concentration under 0.05 mM or 5 mM nitrogen regimes were 495 mg/l and 1409 mg/l, respectively. We also confirmed that nitrogen limitation increased cellular lipid content up to 35% under 0.05 mM nitrogen concentration. In order to gain insight into the mechanisms of this phenomenon, we applied fluorometric, flow cytometric and spectrophotometric methods to measure oxidative stress and enzymatic defence mechanisms. Under nitrogen depleted cultivation conditions, we observed increased lipid peroxidation by measuring an important oxidative stress marker, malondialdehyde and enhanced activation of catalase, ascorbate peroxidase and superoxide dismutase antioxidant enzymes. These observations indicated that oxidative stress is accompanied by increased lipid content in the green alga. In addition, we also showed that at optimum cultivation conditions, inducing oxidative stress by application of exogenous H2O2 leads to increased cellular lipid content up to 44% when compared with non-treated control groups. Our results support that oxidative stress and lipid overproduction are linked. Importantly, these results also suggest that oxidative stress mediates lipid accumulation. Understanding such relationships may provide guidance for efficient production of algal biodiesels

Nitrogen source, an important determinant of fatty acid accumulation and profile in scenedesmus obliquus

The potential of algae-based fuel technologies for manufacturing renewable biofuels has been attracting interest from the scientific community. Biomass productivity and cellular lipid content are important parameters affecting the feasibility of using algae oil for biodiesel production. This study compares utilization of NaNO3, NH4Cland urea as different nitrogen sources in terms of their effects on biomass productivity, fatty acid profile and accumulation in Scenedesmus obliquus. Cellular lipid accumulation was analyzed by gravimetric, fluorometric, and flow-cytometric methods, besides collecting spectrophotometric data for biomass productivity analysis. In addition, fatty acid profiles were compared by using gas chromatography–mass spectrometry. The alga can utilize all tested nitrogen sources successfully however growth rates demonstrate differences. Gravimetric lipid content analysisshowed approximately a 1.5-fold increase in total lipid accumulation under NH4Cl regime when compared tothat of NaNO3 and a 2-fold increase when compared to that of urea at the end of ten days cultivation course. Fatty acid profiles under different nitrogen regimes present variations especially under NH4Cl regime. Moreover,all lipid extracts mostly consist of saturated, straight- and branched-chain hydrocarbons of different chain lengths ranging from C16–C20 which grant a suitable profile for biodiesel production. Scenedesmus obliquus is a suitable species for biodiesel production. The results obtained from this study provide a better understanding of cultivation characteristics of this important species and support potential, future biodiesel production

The influence of photoperiod and light intensity on the growth and photosynthesis of Dunaliella salina (chlorophyta) CCAP 19/30

The green microalga Dunaliella salina survives in a wide range of salinities via mechanisms involving glycerol synthesis and degradation and is exploited for large amounts of nutraceutical carotenoids produced under stressed conditions. In this study, D. salina CCAP 19/30 was cultured in varying photoperiods and light intensities to study the relationship of light with different growth measurement parameters, with cellular contents of glycerol, starch and carotenoids, and with photosynthesis and respiration. Results show CCAP 19/30 regulated cell volume when growing under light/dark cycles: cell volume increased in the light and decreased in the dark, and these changes corresponded to changes in cellular glycerol content. The decrease in cell volume in the dark was independent of cell division and biological clock and was regulated by the photoperiod of the light/dark cycle. When the light intensity was increased to above 1000 μmol photons m−2 s−1, cells displayed evidence of photodamage. However, these cells also maintained the maximum level of photosynthesis efficiency and respiration possible, and the growth rate increased as light intensity increased. Significantly, the intracellular glycerol content also increased, >2-fold compared to the content in light intensity of 500 μmol photons m−2 s−1, but there was no commensurate increase in the pool size of carotenoids. These data suggest that in CCAP 19/30 glycerol stabilized the photosynthetic apparatus for maximum performance in high light intensities, a role normally attributed to carotenoids

Antimicrobial Drug Interactions: Systematic Evaluation of Protein and Nucleic Acid Synthesis Inhibitors

Antimicrobial multidrug resistance and its transmission among strains are serious problems. Success rate is decreased and treatment options are narrowed due to increasing bacterial multidrug resistance. On the other hand, the need for long-term efforts to discover new antibiotics and difficulties finding new treatment protocols make this problem more complex. Combination therapy, especially with synergistic use of antimicrobials is a rational treatment option with huge benefits. Thus, screening antibiotic interactions is crucial for finding better treatment options. Clinicians currently use combinatorial antibiotic treatment as an effective treatment option. However, antibiotics can show synergistic or antagonistic interactions when used together. In our study, we aimed to investigate interactions of antibiotics with different mechanisms of action. Antibiotics, which act as protein synthesis inhibitors (P) and nucleic acid synthesis inhibitors (N) were used in our study. We tested 66 (PN), 15 (NN), and 55 (PP) drug pairs on the Escherichia coli strain. The Loewe additivity model was used and alpha scores were calculated for analysis of interactions of drug combinations. Drug interactions were categorized as synergistic or antagonistic. Accordingly, pairwise combinations of protein synthesis inhibitors (PP) showed stronger synergistic interactions than those of nucleic acid synthesis inhibitors (NN) and nucleic acid synthesis–protein synthesis inhibitors (PN). As a result, the importance of mechanisms of action of drugs is emphasized in the selection of synergistic drug combinations

Une relation triangulaire : «mère/fille et femme» chez Leyla Erbil et Annie Ernaux

Cette étude comparative sur le thème de la relation mère/ fille est développée autour de deux auteurs : Annie Ernaux et Leyla Erbil, écrivaine contemporaine turque. Ce travail comparatif nous permet de souligner le rôle et la condition de la femme dans deux sociétés différentes : la France et la Turquie.Yilancioglu Seza. Une relation triangulaire : «mère/fille et femme» chez Leyla Erbil et Annie Ernaux. In: Horizons Maghrébins - Le droit à la mémoire, N°60, 2009. Littératures féminines avec et autour de Maïssa Bey. pp. 56-65

ŞİZOFRENİ HASTALARININ GENOMİK VERİ KULLANARAK KLASİFİYE EDİLMESİ; VERİ MADENCİĞİ YAKLAŞIMI

Genomic information obtained from robust analysis methods such as microarray and next generation sequencing reveals underlying disease mediating factors and potential diagnostic biomarkers. Data mining methods have been widely chosen for classification and regression studies of health sciences as well as other disciplines since the beginning. In the present study, public Gene Expression Omnibus (GEO) genome wide expression dataset (ID: GSE12679) consisting of mRNA transcripts of post-mortem brain tissues in schizophrenic and normal patients were analyzed by using Multilayer Perceptron Neural Network (MLP NN) algorithm. A set of most differentially expressed genetic features (p<0.001) were used for creating the classifier which can predict disease states in test set with ~82% accuracy. Differentially expressed genes used as classifying biomarkers gain utmost importance for revealing hidden underlying genetic factors associated with important psychiatric diseases. We could also suggest that such data mining tools might be applicable for developing genome-based diagnostic tool

Genetic, physiological and biotechnological assessment of microorganisms for renewable and sustainable energy resource production

The term "algae" defines variety of photosynthetic organisms found throughout the world in various environmental conditions. Algae species are estimated to number in the tens of thousands. Because algae are photosynthetic, naturally able to replicate rapidly and produce high amount of oils, alcohols, and biomass, they have attracted the attention of researchers and industrial producers seeking alternatives to currently used fossil fuels. Algae thrive on organic carbon or CO2, nutrients such as nitrogen, phosphorus and other inorganic substances which enables algae to be used in bioremediation. Growth conditions, nutrients such as carbon and nitrogen, and many other factors affect the algal cell metabolism. Thus, manipulation of different cultivation conditions have been shown successful in increasing algal biomass and lipid productivity in order to substitute petroleum use. Algae biotechnology research goals especially include finding ways to increase the reproductive rate, improve metabolism of inputs, and enhance the production of desired oils, fuel-grade alcohols in useful species. In this thesis, newly isolated halophilic unicellular green algae species are assessed for potential renewable energy resource. Novel strategies for increasing cellular lipid production were established. Exogenous application of oxidative stress by hydrogen peroxide treatment was shown as a novel lipid accumulation inducer. Moreover, increased lipid accumulation response was also observed in heavy metal induced oxidative stress which makes combination of heavy metal bioremediation and oil production possible as a novel algae cultivation strategy. Directed evolution and natural selection strategies were applied to model organism Saccharomyces cerevisiae and Dunaliella salina for revealing underlying biochemical, genetic factors of increased cellular lipid production in order to provide useful strategies for future biofuel production