Inhibition of MACC1-induced metastasis in esophageal and gastric adenocarcinomas

Esophageal and Gastric Adenocarcinomas (AGE/S) are characterized by early metastasis and poor survival. MACC1 (Metastasis Associated in Colon Cancer 1) acts in colon cancer as a metastasis inducer and is linked to reduced survival. This project illuminates the role and potential for the inhibition of MACC1 in AGE/S. Using 266 of 360 TMAs and survival data of AGE/S patients, we confirm the value of MACC1 as an independent negative prognostic marker in AGE/S patients. MACC1 gene expression is correlated with survival and morphological characteristics. In vitro analysis of lentivirally MACC1-manipulated subclones of FLO-1 and OE33 showed enhanced migration induced by MACC1 in both cell line models, which could be inhibited by the MEK1 inhibitor selumetinib. In vivo, the efficacy of selumetinib on tumor growths and metastases of MACC1-overexpressing FLO-1 cells xenografted intrasplenically in NOG mice was tested. Mice with high-MACC1-expressing cells developed faster and larger distant metastases. Treatment with selumetinib led to a significant reduction in metastasis exclusively in the MACC1-positive xenografts. MACC1 is an enhancer of tumor aggressiveness and a predictor of poor survival in AGE/S. This effect can be inhibited by selumetinib

Fertilizing Nature: A Tragedy of Excess in the Commons

Why has nitrogen fertilizer use declined in some countries while increasing in others, despite significant environmental harm? Proper crop management strategies offer environmental and economic benefits without sacrificing yields

Synoptic transects on the distribution of trace elements (Hg, Pb, Cd, Cu, Ni, Zn, Co, Mn, Fe, and Al) in surface waters of the Northern- and Southern East Atlantic

Surface seawater samples were taken in the framework of the GEOTRACES program on “POLARSTERN” expedition ANT XXIII/1 in the Eastern Atlantic in 2005 to study the distribution of the trace elements Hg (mercury), Pb (lead), Cd (cadmium), Cu (copper), Ni (nickel), Zn (zinc), Co (cobalt), Mn (manganese), Fe (iron), and Al (aluminium). With the exception of Hg, results were compared to earlier datasets from 1989 to 1990. The particulate fraction averaged over the transect was calculated to be 49% for Cd, 23% for Mn and 50% for Fe indicating a release of these TEI's (trace elements and their isotopes) from a leachable SPM fraction in the stored and acidified samples. Total Pb concentrations ranged between 5 and 20 pmol kg− 1 in 2005 with highest values in the ITCZ (intertropical convergence zone). In 1989 Pb concentrations were twice as high in the region of the ITCZ, while by a factor of 10–15 higher values were obtained in the North Atlantic. Total Cd and Co are dominated, by different seasonal upwelling regimes (Equatorial upwelling, Guinea Dome, Angola Dome). Total Cu, Ni, Fe, Mn and Al show nearly identical concentrations in 1990 and 2005. For total manganese and aluminium strong maxima (3–4 nmol kg− 1 and 55 nmol kg− 1 respectively) are observed between 23°N and 0°, while the Fe maximum (6–9 nmol kg− 1) is located at 7°N. Total Hg concentrations ranged between 0.5 and 4.5 pmol kg− 1

Forest adjacent households’ voices on their perceptions and adaptation strategies to climate change in Kilombero District, Tanzania

Climate change is a global and local challenge to both sustainable livelihoods and economic development. Tanzania as other countries of the world has been affected. Several studies have been conducted on farmers’ perceptions and adaptation to climate change in the country, but little attention has been devoted to forest adjacent households in humid areas. This study assessed this gap through assessing forest adjacent households’ voices on perceptions and adaptation strategies to climate change in Kilombero District, Tanzania. Data collection involved key informant interviews, focus group discussions and household questionnaires. Results showed that the majority of households perceived changed climate in terms of temperature increase, unpredictable rainfall, frequent occurrence of floods, increased dry spells during rainy season coupled with decreased water sources and emergence of new pests and diseases. The perceived change in climate has impacted agriculture productivity as the main livelihood source. Different coping and adaptation strategies are employed. These are; crop diversification, changing cropping calendar, adopting modern farming technologies, and increasing reliance on non-timber forest products. These strategies were positively and significantly influenced by socio-economic factors including household size, residence period, land ownership and household income. The study concludes that, there are changes in climatic conditions; and to respond to these climatic changes, forest adjacent households have developed numerous coping and adaptation strategies, which were positively and significantly influenced by some socio-economic factors. The study calls for actual implementation of local climate change policies and strategies in order to enhance adaptive capacity at household level