Cytotoxicity, cell cycle arrest, and apoptosis in breast cancer cell lines exposed to an extract of the seed kernel of Mangifera pajang (bambangan).

An extract of Mangifera pajang kernel has been previously found to contain a high content of antioxidant phytochemicals. The present research was conducted to investigate the anticancer potential of this kernel extract. The results showed that the kernel crude extract induced cytotoxicity in MCF-7 (hormone-dependent breast cancer) cells and MDA-MB-231 (non-hormone dependent breast cancer) cells with IC50 values of 23 and 30.5μg/ml, respectively. The kernel extract induced cell cycle arrest in MCF-7 cells at the sub-G1 (apoptosis) phase of the cell cycle in a time-dependent manner. For MDA-MB-231 cells, the kernel extract induced strong G2-M arrest in cell cycle progression at 24. h, resulting in substantial sub-G1 (apoptosis) arrest after 48 and 72. h of incubation. Staining with Annexin V-FITC and propidium iodide revealed that this apoptosis occurred early in both cell types, 36. h for MCF-7 cells and 24. h for MDA-MB-231cells, with 14.0% and 16.5% of the cells respectively undergoing apoptosis at these times. This apoptosis appeared to be dependent on caspase-2 and -3 in MCF-7 cells, and on caspase-2, -3 and -9 in MDA-MB-231 cells. These findings suggest that M. pajang kernel extract has potential as a potent cytotoxic agent against breast cancer cell lines

Cytotoxicity and polyphenol diversity in selected parts of Mangifera pajang and Artocarpus odoratissimus fruits.

Purpose Research on cancer chemopreventive properties of fruits has increased in recent years. Polyphenols have been suggested to exert such effects. The purpose of this paper is to determine the cytotoxic activity of Mangifera pajang (bambangan) and Artocarpus odoratissimus (tarap) crude extracts against selected cancer cell lines (i.e. ovarian, liver and colon cancer) and to compare the amount of selected polyphenols (phenolic acids, flavanones, flavonols and flavones) in the kernel, peel and flesh of M. pajang; and the seed and flesh of A. odoratissimus. Design/methodology/approach Cytotoxicity activity of the extracts are investigated using MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay while polyphenols are determined using high performance liquid chromatography. Findings The results show that only the kernel and peel extracts from M. pajang display cytotoxic activity in liver and ovarian cancer cell lines with IC50 values ranging from 34.5 to 92.0  μg/ml. The proliferation of colon cancer cell line is inhibited only by the kernel of M. pajang with IC50 value of 63.0  μg/ml. The kernel and peel from M. pajang contains a broad range of polyphenol phytochemicals which might be responsible for the cytotoxicity activity against selected cancer cell lines. Originality/value Previous reports have indicated that both M. pajang and A. odoratissimus contain high antioxidant properties. This study further determines the phytochemicals profiling in both fruits, which might contribute to the antioxidant activity. Besides that, the result from this study shows that the waste of the fruits (i.e. kernel and peel) contain superior phenolic phytochemicals and display better anticancer potential compared to the flesh; suggests the use of them in health‐industry application. Utilization of all parts of the fruits (i.e. flesh, seed, kernel and peel) for the development of nutraceutical and functional food application is suggested

The aerodynamics of hovering flight in Drosophila

Using 3D infrared high-speed video, we captured the continuous wing and body kinematics of free-flying fruit flies, Drosophila melanogaster, during hovering and slow forward flight. We then `replayed' the wing kinematics on a dynamically scaled robotic model to measure the aerodynamic forces produced by the wings. Hovering animals generate a U-shaped wing trajectory, in which large drag forces during a downward plunge at the start of each stroke create peak vertical forces. Quasi-steady mechanisms could account for nearly all of the mean measured force required to hover, although temporal discrepancies between instantaneous measured forces and model predictions indicate that unsteady mechanisms also play a significant role. We analyzed the requirements for hovering from an analysis of the time history of forces and moments in all six degrees of freedom. The wing kinematics necessary to generate sufficient lift are highly constrained by the requirement to balance thrust and pitch torque over the stroke cycle. We also compare the wing motion and aerodynamic forces of free and tethered flies. Tethering causes a strong distortion of the stroke pattern that results in a reduction of translational forces and a prominent nose-down pitch moment. The stereotyped distortion under tethered conditions is most likely due to a disruption of sensory feedback. Finally, we calculated flight power based directly on the measurements of wing motion and aerodynamic forces, which yielded a higher estimate of muscle power during free hovering flight than prior estimates based on time-averaged parameters. This discrepancy is mostly due to a two- to threefold underestimate of the mean profile drag coefficient in prior studies. We also compared our values with the predictions of the same time-averaged models using more accurate kinematic and aerodynamic input parameters based on our high-speed videography measurements. In this case, the time-averaged models tended to overestimate flight costs

HETDEX pilot survey for emission-line galaxies - I. Survey design, performance, and catalog

We present a catalog of emission-line galaxies selected solely by their emission-line fluxes using a wide-field integral field spectrograph. This work is partially motivated as a pilot survey for the upcoming Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). We describe the observations, reductions, detections, redshift classifications, line fluxes, and counterpart information for 397 emission-line galaxies detected over 169 sq.arcmin with a 3500-5800 Ang. bandpass under 5 Ang. full-width-half-maximum (FWHM) spectral resolution. The survey's best sensitivity for unresolved objects under photometric conditions is between 4-20 E-17 erg/s/sq.cm depending on the wavelength, and Ly-alpha luminosities between 3-6 E42 erg/s are detectable. This survey method complements narrowband and color-selection techniques in the search for high redshift galaxies with its different selection properties and large volume probed. The four survey fields within the COSMOS, GOODS-N, MUNICS, and XMM-LSS areas are rich with existing, complementary data. We find 104 galaxies via their high redshift Ly-alpha emission at 1.9<z<3.8, and the majority of the remainder objects are low redshift [OII]3727 emitters at z<0.56. The classification between low and high redshift objects depends on rest frame equivalent width, as well as other indicators, where available. Based on matches to X-ray catalogs, the active galactic nuclei (AGN) fraction amongst the Ly-alpha emitters (LAEs) is 6%. We also analyze the survey's completeness and contamination properties through simulations. We find five high-z, highly-significant, resolved objects with full-width-half-maximum sizes >44 sq.arcsec which appear to be extended Ly-alpha nebulae. We also find three high-z objects with rest frame Ly-alpha equivalent widths above the level believed to be achievable with normal star formation, EW(rest)>240 Ang.Comment: 45 pages, 36 figures, 5 tables, submitted to ApJ

The lifetime of nitrogen oxides in an isoprene-dominated forest

The lifetime of nitrogen oxides (NO_x) affects the concentration and distribution of NO_x and the spatial patterns of nitrogen deposition. Despite its importance, the lifetime of NO_x is poorly constrained in rural and remote continental regions. We use measurements from a site in central Alabama during the Southern Oxidant and Aerosol Study (SOAS) in summer 2013 to provide new insights into the chemistry of NO_x and NO_x reservoirs. We find that the lifetime of NO_x during the daytime is controlled primarily by the production and loss of alkyl and multifunctional nitrates (ΣANs). During SOAS, ΣAN production was rapid, averaging 90 ppt h^(−1) during the day, and occurred predominantly during isoprene oxidation. Analysis of the ΣAN and HNO_3 budgets indicate that ΣANs have an average lifetime of under 2 h, and that approximately 45 % of the ΣANs produced at this site are rapidly hydrolyzed to produce nitric acid. We find that ΣAN hydrolysis is the largest source of HNO_3 and the primary pathway to permanent removal of NO_x from the boundary layer in this location. Using these new constraints on the fate of ΣANs, we find that the NO_x lifetime is 11 ± 5 h under typical midday conditions. The lifetime is extended by storage of NO_x in temporary reservoirs, including acyl peroxy nitrates and ΣANs

Complex I-Associated Hydrogen Peroxide Production Is Decreased and Electron Transport Chain Enzyme Activities Are Altered in n-3 Enriched fat-1 Mice

The polyunsaturated nature of n-3 fatty acids makes them prone to oxidative damage. However, it is not clear if n-3 fatty acids are simply a passive site for oxidative attack or if they also modulate mitochondrial reactive oxygen species (ROS) production. The present study used fat-1 transgenic mice, that are capable of synthesizing n-3 fatty acids, to investigate the influence of increases in n-3 fatty acids and resultant decreases in the n-6∶n-3 ratio on liver mitochondrial H2O2 production and electron transport chain (ETC) activity. There was an increase in n-3 fatty acids and a decrease in the n-6∶n-3 ratio in liver mitochondria from the fat-1 compared to control mice. This change was largely due to alterations in the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine, with only a small percentage of fatty acids in cardiolipin being altered in the fat-1 animals. The lipid changes in the fat-1 mice were associated with a decrease (p<0.05) in the activity of ETC complex I and increases (p<0.05) in the activities of complexes III and IV. Mitochondrial H2O2 production with either succinate or succinate/glutamate/malate substrates was also decreased (p<0.05) in the fat-1 mice. This change in H2O2 production was due to a decrease in ROS production from ETC complex I in the fat-1 animals. These results indicate that the fatty acid changes in fat-1 liver mitochondria may at least partially oppose oxidative stress by limiting ROS production from ETC complex I

System Dynamics to Model the Unintended Consequences of Denying Payment for Venous Thromboembolism after Total Knee Arthroplasty

Background: The Hospital Acquired Condition Strategy (HACS) denies payment for venous thromboembolism (VTE) after total knee arthroplasty (TKA). The intention is to reduce complications and associated costs, while improving the quality of care by mandating VTE prophylaxis. We applied a system dynamics model to estimate the impact of HACS on VTE rates, and potential unintended consequences such as increased rates of bleeding and infection and decreased access for patients who might benefit from TKA. Methods and Findings: The system dynamics model uses a series of patient stocks including the number needing TKA, deemed ineligible, receiving TKA, and harmed due to surgical complication. The flow of patients between stocks is determined by a series of causal elements such as rates of exclusion, surgery and complications. The number of patients harmed due to VTE, bleeding or exclusion were modeled by year by comparing patient stocks that results in scenarios with and without HACS. The percentage of TKA patients experiencing VTE decreased approximately 3-fold with HACS. This decrease in VTE was offset by an increased rate of bleeding and infection. Moreover, results from the model suggest HACS could exclude 1.5% or half a million patients who might benefit from knee replacement through 2020. Conclusion: System dynamics modeling indicates HACS will have the intended consequence of reducing VTE rates. However, an unintended consequence of the policy might be increased potential harm resulting from over administration of prophylaxis, as well as exclusion of a large population of patients who might benefit from TKA

Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal Streptococcus pneumoniae: A Cluster-Randomized Clinical Trial

Jeremy Keenan and colleagues report that during a cluster-randomized clinical trial in Ethiopia, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to receive azithromycin compared with untreated control communities