Cell cycle regulation of redoxyendonuclease activity in human neuroblastoma cells.

Redoxyendonuclease activity was detected in extracts of human neuroblastoma cells using a base-release assay specific for thymine glycol in DNA. The level of redoxyendonuclease activity was more than 2-fold higher in dividing cells compared to quiescent cells, suggesting that quiescent cells may have a reduced capacity to repair oxidative DNA base damages. Cells were synchronized by serum deprivation and then stimulated to enter the cell cycle by the addition of serum to determine enzyme activity at different stages of the cell cycle. The redoxyendonuclease activity was regulated in a biphasic manner with a peak in early G1 and a peak in S phase. This suggests that at specific times during the cell cycle actively growing cells may be more resistant to oxidative DNA damage due to increased repair capacity. The repair capacity of neuroblastoma cells was quantified as the decrease in enzyme-sensitive sites determined by alkaline sucrose density gradient centrifugation following treatment with the oxidant osmium tetroxide. Actively dividing cells repaired the oxidative damage in approximately 24 hours, while the quiescent cells failed to excise the damaged sites and subsequently died. These results indicate that non-dividing cells do not effectively repair oxidative DNA damage, as compared to the dividing cells. Similarly, quiescent cells, treated with osmium tetroxide and fed a serum-enriched media, failed to re-enter the cell cycle and did not repair the oxidative damage. The data indicate that non-dividing cells, such as neurons, do not have the capacity to repair excess oxidative damage and may suffer the biological consequences of DNA damage accumulation, including cellular death, mutagenesis or carcinogenesis. When synchronized cells were damaged with osmium tetroxide, there were differential DNA repair rates, depending on the stage of the cell cycle. These DNA repair rates coordinated with the redoxyendonuclease activity profile. The results of the studies described contribute to a further understanding of the DNA repair pathways which are interlinked with complex processes of cell cycle regulation

Turmeric and Ginger as Health Protective Food Sources - An Integrative Review

Most of the medicinal plants utilized in traditional medicine are spices. Majority of those spices are widely used for aroma, flavour and colour in cuisine though they behave as appetizers, digestives, preventives and aphrodisiacs. Their antimicrobial properties are in a broad spectrum that provides a considerable immunity development within the human body. This review summarizes the beneficial characteristics of major active constituents in turmeric and ginger and their presumed pharmacological potential to safeguard human health.Keywords: Turmeric, Ginger, Curcumin, Human health, Active Ingredients, Nanotechnolog

Distribution Of Hydrological Losses For Varying Rainfall And Antecedent Wetness Conditions

Hydrological loss is a vital component in many hydrological models, which are usedin forecasting floods and evaluating water resources for both surface and subsurface flows. Due to the complex and random nature of the rainfall runoff process, hydrological losses are not yet fully understood. Consequently, practitioners often use representative values of the losses for design applications such as rainfall-runoff modelling which has led to inaccurate quantification of water quantities in the resulting applications. The existing hydrological loss models must be revisited and modellers should be encouraged to utilise other available data sets. This study is based on three unregulated catchments situated in Mt. Lofty Ranges of South Australia (SA). The paper focuses on conceptual models for: initial loss (IL), continuing loss (CL) and proportional loss (PL) with rainfall characteristics (total rainfall (TR) and storm duration (D)), and antecedent wetness (AW) conditions. The paper introduces two methods that can be implemented to estimate IL as a function of TR, D and AW. The IL distribution patterns and parameters for the study catchments are determined using multivariate analysis and descriptive statistics. The possibility of generalising the methods and the limitations of this are also discussed. This study will yield improvements to existing loss models and will encourage practitioners to utilise multiple data sets to estimate losses, instead of using hypothetical or representative values to generalise real situations

Mechanistic Study Of The Photochemical Hydroxide Ion Release From 9-hydroxy-10-methyl-9-phenyl-9,10-dihydroacridine

The excited-state behavior of 9-hydroxy-10-methyl-9-phenyl-9,10-dihydroacridine and its derivative, 9-methoxy-10-methyl-9-phenyl-9,10-dihydroacridine (AcrOR, R = H, Me), was studied via femtosecond and nanosecond UV-vis transient absorption spectroscopy. The solvent effects on C-O bond cleavage were clearly identified: a fast heterolytic cleavage (tau = 108 ps) was observed in protic solvents, while intersystem crossing was observed in aprotic solvents. Fast heterolysis generates 10methyl-9-phenylacridinium (Acr(+)) and -OH, which have a long recombination lifetime (no signal decay was observed within 100 mu s). AcrOH exhibits the characteristic behavior needed for its utilization as a chromophore in the pOH jump experiment

Maternal thyroid hormones are essential for neural development in Zebrafish

Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and early in zebrafish embryonic development, all the genes necessary for TH signaling are expressed. Nonetheless the function of THs in embryonic development remains elusive. To test the hypothesis that THs are fundamental for zebrafish embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy was deployed to prevent maternal TH uptake. Absence of maternal THs did not affect early specification of the neural epithelia but profoundly modified later dorsal specification of the brain and spinal cord as well as specific neuron differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord interneurons and increased motoneurons in the mct8 morphants is consistent with their stiff axial body and impaired mobility. The mct8 mutations are associated with X-linked mental retardation in humans, and the cellular and molecular consequences of MCT8 knockdown during embryonic development in zebrafish provides new insight into the potential role of THs in this condition.Portuguese Science Foundation (FCT) [PTDC/MAR/115005/2009]; FCT [SFRH/BPD/66808/2009, SFRH/BPD/67008/2009, Pest-OE/EQB/LA0023/2013]info:eu-repo/semantics/publishedVersio

Multiplex Cytological Profiling Assay to Measure Diverse Cellular States

Computational methods for image-based profiling are under active development, but their success hinges on assays that can capture a wide range of phenotypes. We have developed a multiplex cytological profiling assay that “paints the cell” with as many fluorescent markers as possible without compromising our ability to extract rich, quantitative profiles in high throughput. The assay detects seven major cellular components. In a pilot screen of bioactive compounds, the assay detected a range of cellular phenotypes and it clustered compounds with similar annotated protein targets or chemical structure based on cytological profiles. The results demonstrate that the assay captures subtle patterns in the combination of morphological labels, thereby detecting the effects of chemical compounds even though their targets are not stained directly. This image-based assay provides an unbiased approach to characterize compound- and disease-associated cell states to support future probe discovery