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

The Link Between Health Insurance Coverage and Citizenship Among Immigrants: Bayesian Unit-Level Regression Modeling of Categorical Survey Data Observed with Measurement Error

Social scientists are interested in studying the impact that citizenship status has on health insurance coverage among immigrants in the United States. This can be done using data from the Survey of Income and Program Participation (SIPP); however, two primary challenges emerge. First, statistical models must account for the survey design in some fashion to reduce the risk of bias due to informative sampling. Second, it has been observed that survey respondents misreport citizenship status at nontrivial rates. This too can induce bias within a statistical model. Thus, we propose the use of a weighted pseudo-likelihood mixture of categorical distributions, where the mixture component is determined by the latent true response variable, in order to model the misreported data. We illustrate through an empirical simulation study that this approach can mitigate the two sources of bias attributable to the sample design and misreporting. Importantly, our misreporting model can be further used as a component in a deeper hierarchical model. With this in mind, we conduct an analysis of the relationship between health insurance coverage and citizenship status using data from the SIPP

Biodisponibilidad de fósforo en un suelo del sur de Santa Fe (Argentina). Efectos de dos fuentes fosfatadas y sus mezclas con urea

Los objetivos de este trabajo fueron: i) determinar en qué medida las fuentes fosfatadas y sus mezclas con urea afectan la biodisponibilidad de P, ii) analizar los efectos de interacción urea/fuente fosfatada, y iii) analizar el efecto de la ureas obre el P nativo del suelo.El experimento se condujo en un Hapludol típico Serie Santa Isabel (pH 6,1; 29 g kg-1 de materia orgánica; 12,4 mg kg-1 de P extractable;P total, 446 mg kg-1; MBC 35,8 L kg-1). Se hicieron ensayos de fertilización de trigo con dos fuentes fosfatadas: fosfato monoamónico y fosfato diamónico endosis de 0, 9 y 17 kg P/ha, en mezclas físicas con urea en dosis de 0, 19 y 37 kgN/ha. Se concluyó que la aplicación de urea no causa efectos sobre los tenores de fósforo nativo en la zona de aplicación. Además, la disponibilidad del fósforo aplicado varía con la dosis y fuente fosfatada utilizada: la aplicación de fosfato monoamónico aumenta significativamente la biodisponibilidad del nutriente en este suelo, con respecto al fosfato diamónico. La utilización de mezclas de fertilizantes fosfatados, con bajas dosis de urea, aumenta la biodisponibilidad del nutriente para el trigo, con relación a las aplicaciones fosfatadas puras

Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival

Characterization of the chemical signatures of air masses observed during the PEM experiments over the western Pacific

Extensive observations of tropospheric trace species during the second NASA Global Tropospheric Experiment Western Pacific Exploratory Mission (PEM-West B) in February-March 1994 showed significant seasonal variability in comparison with the first mission (PEM-West A), conducted in September-October 1991. In this study we adopt a previously established analytical method, i.e., the ratio C2H2/CO as a measure of the relative degree of atmospheric processing, to elucidate the key similarities and variations between the two missions. In addition, the C2H2/CO ratio scheme is combined with the back-trajectory-based and the LIDAR-based air mass classification schemes, respectively, to make in-depth analysis of the seasonal variation between PEM-West A and PEM-West B (hereinafter referred to as PEM-WA and PEM-WB). A large number of compounds, including long-lived NMHCs, CH4, and CO2, are, as expected, well correlated with the ratio C2H2/CO. In comparison with PEM-WA, a significantly larger range of observed C2H2/CO values at the high end for the PEM-WB period indicates that the western Pacific was more impacted by "fresher" source emissions, i.e., faster or more efficient continental outflow. As in the case of PEM-WA, the C2H2/CO scheme complements the back-trajectory air mass classification scheme very well. By combining the two schemes, we found that the atmospheric processing in the region is dominated by atmospheric mixing for the trace species analyzed. This PEM-WB wintertime result is similar to that found in PEM-WA for the autumn. In both cases, photochemical reactions are found to play a significant role in determining the background mixing ratios of trace gases, and in this way the two processes are directly related and dependent upon each other. This analysis also indicates that many of the upper tropospheric air masses encountered over the western Pacific during PEM-WB may have had little impact from eastern Asia's continental surface sources. NOx mixing ratios were significantly enhanced during PEM-WB when compared with PEM-WA, in the upper troposphere's more atmospherically processed air masses. These high levels of NOx resulted in a substantial amount of photochemical production of O3. A lack of corresponding enhancements in surface emission tracers strongly implies that in situ atmospheric sources such as lightning are responsible for the enhanced upper tropospheric NOx. The similarity in NOx values between the northern (higher air traffic) and southern continental air masses together with the indications of a large seasonal shift suggests that aircraft emissions are not the dominant source. However, photochemical recycling cannot be ruled out as this in situ source of NOx. Copyright 1999 by the American Geophysical Union

Assessment of ozone photochemistry in the western North Pacific as inferred from PEM-West A observations during the fall 1991

This study examines the influence of photochemical processes on ozone distributions in the western North Pacific. The analysis is based on data generated during NASA's western Pacific Exploratory Mission (PEM-West A) during the fall of 1991. Ozone trends were best described in terms of two geographical domains: the western North Pacific rim (WNPR) and the western tropical North Pacific (WTNP). For both geographical regions, ozone photochemical destruction, D(O3), decreased more rapidly with altitude than did photochemical formation, F(O3). Thus the ozone tendency, P(O3), was typically found to be negative for z <6 km and positive for z > 6-8 km. For nearly all altitudes and latitudes, observed nonmethane hydrocarbon (NMHC) levels were shown to be of minor importance as ozone precursor species. Air parcel types producing the largest positive values of P(O3) included fresh continental boundary layer (BL) air and high-altitude (z > 7 km) parcels influenced by deep convection/lightning. Significant negative P(O3) values were found when encountering clean marine BL air or relatively clean lower free-tropospheric air. Photochemical destruction and formation fluxes for the Pacific rim region were found to exceed average values cited for marine dry deposition and stratospheric injection in the northern hemisphere by nearly a factor of 6. This region was also found to be in near balance with respect to column-integrated O3 photochemical production and destruction. By contrast, for the tropical regime column-integrated O3 showed photochemical destruction exceeding production by nearly 80%. Both transport of O3 rich midlatitude air into the tropics as well as very high-altitude (10-17 km) photochemical O3 production were proposed as possible additional sources that might explain this estimated deficit. Results from this study further suggest that during the fall time period, deep convection over Asia and Malaysia/Indonesia provided a significant source of high-altitude NOx to the western Pacific. Given that the high-altitude NOx lifetime is estimated at between 3 and 9 days, one would predict that this source added significantly to high altitude photochemical O3 formation over large areas of the western Pacific. When viewed in terms of strong seasonal westerly flow, its influence would potentially span a large part of the Pacific. Copyright 1996 by the American Geophysical Union

Development of Resistance towards Artesunate in MDA-MB-231 Human Breast Cancer Cells

Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate, clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of artesunate in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, artesunate induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abolishment of apoptosis and cytotoxicity in pre-treated MDA-MB-231 cells. In contrast, artesunate was more cytotoxic towards the less tumorigenic MDA-MB-468 cells without showing resistance. Unraveling the underlying molecular mechanisms, we found that resistance was induced due to activation of the tumor progression related transcription factors NFκB and AP-1. Thereby transcription, expression and activity of the matrix-degrading enzyme MMP-1, whose function is correlated with increased invasion and metastasis, was up-regulated upon acquisition of resistance. Additionally, activation of the apoptosis-related factor NFκB lead to increased expression of ant-apoptotic bcl2 and reduced expression of pro-apoptotic bax. Application of artesunate in vivo in a model of xenografted breast cancer showed, that tumors growth was not efficiently abolished as compared to the control drug doxorubicin. Taken together our in vitro and in vivo results correlate well showing for the first time that artesunate induces resistance in highly metastatic breast tumors

Atmospheric sampling of Supertyphoon Mireille with NASA DC-8 aircraft on September 27,1991, during PEM-West A

The DC-8 mission of September 27, 1991, was designed to sample air flowing into Typhoon Mireille in the boundary layer, air in the upper tropospheric eye region, and air emerging from the typhoon and ahead of the system, also in the upper troposphere. The objective was to find how a typhoon redistributes trace constituents in the West Pacific region and whether any such redistribution is important on the global scale. The boundary layer air (300 m), in a region to the SE of the eye, contained low mixing ratios of the tracer species O3, CO, C2H6, C2H2, C3H8, C6H6and CS2 but high values of dimethylsulfide (DMS). The eye region relative to the boundary layer, showed somewhat elevated levels of CO, substantially increased levels of O3, CS2 and all nonmethane hydrocarbons (NMHCs), and somewhat reduced levels of DMS. Ahead of the eye, CO and the NMHCs remained unchanged, O3 and CS2 showed a modest decrease, and DMS showed a substantial decrease. There was no evidence from lidar cross sections of ozone for the downward entrainment of stratospheric air into the eye region; these sections show that low ozone values were measured in the troposphere. The DMS data suggest substantial entrainment of boundary layer air into the system, particularly into the eye wall region. Estimates of the DMS sulphur flux between the boundary layer and the free troposphere, based on computations of velocity potential and divergent winds, gave values of about 69 μg S m−2 d−1 averaged over a 17.5° grid square encompassing the typhoon. A few hours after sampling with the DC-8, Mireille passed over Oki Island, just to the north of Japan, producing surface values of ozone of 5.5 ppbv. These O3 levels are consistent with the low tropospheric values found by lidar and are more typical of equatorial regions. We suggest that the central eye region may act like a Taylor column which has moved poleward from low latitudes. The high-altitude photochemical environment within Typhoon Mireille was found to be quite active as evidenced by significant levels of measured gas phase H2O2 and CH3OOH and model-computed levels of OH

Intrinsic regulation of hemangioma involution by platelet-derived growth factor

Infantile hemangioma is a vascular tumor that exhibits a unique natural cycle of rapid growth followed by involution. Previously, we have shown that hemangiomas arise from CD133+ stem cells that differentiate into endothelial cells when implanted in immunodeficient mice. The same clonally expanded stem cells also produced adipocytes, thus recapitulating the involuting phase of hemangioma. In the present study, we have elucidated the intrinsic mechanisms of adipocyte differentiation using hemangioma-derived stem cells (hemSCs). We found that platelet-derived growth factor (PDGF) is elevated during the proliferating phase and may inhibit adipocyte differentiation. hemSCs expressed high levels of PDGF-B and showed sustained tyrosine phosphorylation of PDGF receptors under basal (unstimulated) conditions. Inhibition of PDGF receptor signaling caused enhanced adipogenesis in hemSCs. Furthermore, exposure of hemSCs to exogenous PDGF-BB reduced the fat content and the expression of adipocyte-specific transcription factors. We also show that these autogenous inhibitory effects are mediated by PDGF receptor-β signaling. In summary, this study identifies PDGF signaling as an intrinsic negative regulator of hemangioma involution and highlights the therapeutic potential of disrupting PDGF signaling for the treatment of hemangiomas

Is the rotation of the femural head a potential initiation for cutting out? A theoretical and experimental approach

We conclude the center-center position in the head of femur of any kind of lag screw or blade is to be achieved to minimize rotation of the femoral head and to prevent further mechanical complications