The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

A bacterial chloroform reductive dehalogenase: purification and biochemical characterization

© 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology. We report herein the purification of a chloroform (CF)-reducing enzyme, TmrA, from the membrane fraction of a strict anaerobe Dehalobacter sp. strain UNSWDHB to apparent homogeneity with an approximate 23-fold increase in relative purity compared to crude lysate. The membrane fraction obtained by ultracentrifugation was solubilized in Triton X-100 in the presence of glycerol, followed by purification by anion exchange chromatography. The molecular mass of the purified TmrA was determined to be 44.5 kDa by SDS-PAGE and MALDI-TOF/TOF. The purified dehalogenase reductively dechlorinated CF to dichloromethane in vitro with reduced methyl viologen as the electron donor at a specific activity of (1.27 ± 0.04) × 103units mg protein−1. The optimum temperature and pH for the activity were 45°C and 7.2, respectively. The UV-visible spectrometric analysis indicated the presence of a corrinoid and two [4Fe-4S] clusters, predicted from the amino acid sequence. This is the first report of the production, purification and biochemical characterization of a CF reductive dehalogenase

A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic

Sewage, a complex mixture of organic and inorganic chemicals, is considered to be a major source of environmental pollution. A random screen of 20 organic man-made chemicals present in liquid effluents revealed that half appeared able to interact with the estradiol receptor. This was demonstrated by their ability to inhibit binding of 17 beta-estradiol to the fish estrogen receptor. Further studies, using mammalian estrogen screens in vitro, revealed that the two phthalate esters butylbenzyl phthalate (BBP) and di-n-butylphthalate (DBP) and a food antioxidant, butylated hydroxyanisole (BHA) were estrogenic; however, they were all less estrogenic than the environmental estrogen octylphenol. Phthalate esters, used in the production of various plastics (including PVC), are among the most common industrial chemicals. Their ubiquity in the environment and tendency to bioconcentrate in animal fat are well known. Neither BBP nor DBP were able to act as antagonists, indicating that, in the presence of endogenous estrogens, their overall effect would be cumulative. Recently, it has been suggested that environmental estrogens may be etiological agents in several human diseases, including disorders of the male reproductive tract and breast and testicular cancers. The current finding that some phthalate compounds and some food additives are weakly estrogenic in vitro, needs to be supported by further studies on their effects in vivo before any conclusions can be made regarding their possible role in the development of these condition

Solar Wind and its Evolution

By using our previous results of magnetohydrodynamical simulations for the solar wind from open flux tubes, I discuss how the solar wind in the past is different from the current solar wind. The simulations are performed in fixed one-dimensional super-radially open magnetic flux tubes by inputing various types of fluctuations from the photosphere, which automatically determines solar wind properties in a forward manner. The three important parameters which determine physical properties of the solar wind are surface fluctuation, magnetic field strengths, and the configuration of magnetic flux tubes. Adjusting these parameters to the sun at earlier times in a qualitative sense, I infer that the quasi-steady-state component of the solar wind in the past was denser and slightly slower if the effect of the magneto-centrifugal force is not significant. I also discuss effects of magneto-centrifugal force and roles of coronal mass ejections.Comment: 6 pages, 1 figure, Earth, Planets, & Space in press (based on 5th Alfven Conference) correction of discussion on a related pape

Green Function on the q-Symmetric Space SU_q(2)/U(1)

Following the introduction of the invariant distance on the non-commutative C-algebra of the quantum group SU_q(2), the Green function and the Kernel on the q-homogeneous space M=SU(2)_q/U(1) are derived. A path integration is formulated. Green function for the free massive scalar field on the non-commutative Einstein space R^1xM is presented.Comment: Plain Latex, 19

Convergence and stability theorems for the Picard-Mann hybrid iterative scheme for a general class of contractive-like operators

In this paper we use the general class of contractive-like operators introduced by Bosede and Rhoades (J. Adv. Math. Stud. 3(2):1-3, 2010) to prove strong convergence and stability results for Picard-Mann hybrid iterative schemes considered in a real normed linear space. We establish the strong convergence and stability of the Picard iterative scheme as a corollary. Our results generalize and improve a multitude of results in the literature, including the recent results of Chidume (Fixed Point Theory Appl. 2014:233, 2014)

KamLAND Sensitivity to Neutrinos from Pre-Supernova Stars

In the late stages of nuclear burning for massive stars (M>8~M_{\sun}), the production of neutrino-antineutrino pairs through various processes becomes the dominant stellar cooling mechanism. As the star evolves, the energy of these neutrinos increases and in the days preceding the supernova a significant fraction of emitted electron anti-neutrinos exceeds the energy threshold for inverse beta decay on free hydrogen. This is the golden channel for liquid scintillator detectors because the coincidence signature allows for significant reductions in background signals. We find that the kiloton-scale liquid scintillator detector KamLAND can detect these pre-supernova neutrinos from a star with a mass of 25~M_{\sun} at a distance less than 690~pc with 3$\sigma$ significance before the supernova. This limit is dependent on the neutrino mass ordering and background levels. KamLAND takes data continuously and can provide a supernova alert to the community.Comment: 19 pages, 6 figures, 1 tabl

Integrated stratigraphy of the Waitakian-Otaian Stage boundary stratotype, Early Miocene, New Zealand

The base of the type section of the Otaian Stage at Bluecliffs, South Canterbury, is recognised as the stratotype for the boundary between the Waitakian and Otaian Stages. Principal problems with the boundary are the restriction of existing bioevent proxies to shelf and upper slope environments and its uncertain age. These topics are addressed by a multidisplinary study of a 125 m section about the boundary, which examines its lithostratigraphy, depositional setting, biostratigraphy, correlation, and geochronology. The lower siltstone lithofacies (0-38.5 m) was deposited at upper bathyal depths (200-600 m) in a marginal basin which was partially sheltered from fully oceanic circulation by a submarine high and islands. The site was covered by cool-temperate water and was probably adjacent to the Subtropical Convergence. This unit is succeeded by the banded lithofacies (38.5-106 m) and the upper siltstone lithofacies (basal 19 m studied). Paleodepth probably declined up-sequence, but deposition at shelf depths is not definitely indicated. A cyclic pattern of abundance spikes in benthic and planktonic foraminifera commences 9 m above base and extends to 73 m in the banded lithofacies. Oxygen isotope excursions (up to 2.08%) in Euuvigerina miozea and Cibicides novozelandicus are greatest within the interval containing the abundance spikes. The stage boundary occurs in the banded lithofacies at the highest abundance spike (73 m). Although condensed intervals might affect the completeness of the section, they are not associated with sedimentary discontinuities, and we consider that the section is suitable as a biostratigraphic reference. Spores, pollens, dinoflagellates, calcareous nannofossils, foraminifera, bryozoans, and ostracods are preserved near the boundary, but molluscs principally occur higher, in the shallower upper siltstone lithofacies. Siliceous microfossils are rare. There is considerable scope for further biostratigraphic research. The primary event marking the boundary at 73 m is the appearance of the benthic foraminifer Ehrenbergina marwicki. This is a distinctive and widely distributed event but is restricted to shelf and upper bathyal environments. Supplementary events in planktonic foraminifera and calcareous nannofossils were researched. Highest occurrences of Globigerina brazieri and G. euapertura are recorded at 47 and 58 m. There is a marked decline in relative abundance of Paragloborotalia spp. at 62 m. Helicosphaera carteri becomes more abundant than H. euphratis between 56 and 87 m. These events are not exact proxies for the boundary but they may usefully indicate proximity to it. They occur in the interval of prominent spikes in foraminiferal abundance. The Waitakian-Otaian boundary is dated at 21.7 Ma by strontium isotopes. Stable primary remanence could not be determined in a pilot paleomagnetic study of Bluecliffs specimens. However, specimens trended towards reversed polarity, and remagnetisation great circle analysis will allow directions to be calculated in future collections