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β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis
Jing Liu1,
Ye Zhang1,
Jinglei Qu1,
Ling Xu1,
Kezuo Hou1,
Jingdong Zhang1,
Xiujuan Qu1 &
Yunpeng Liu1
β-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which β-elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of β-elemene on human gastric cancer cells and the molecular mechanism involved.
β-Elemene inhibited the viability of human gastric cancer MGC803 and SGC7901 cells in a dose-dependent manner. The suppression of cell viability was due to the induction of apoptosis. A robust autophagy was observed in the cells treated with β-elemene; it was characterized by the increase of punctate LC3 dots, the cellular morphology, and the increased levels of LC3-II protein. Further study showed that β-elemene treatment up-regulated Atg5-Atg12 conjugated protein but had little effect on other autophagy-related proteins. PI3K/Akt/mTOR/p70S6K1 activity was inhibited by β-elemene. Knockdown of Beclin 1 with small interfering RNA, or co-treatment with the autophagy inhibitor, 3-methyladenine or chlorochine enhanced significantly the antitumor effects of β-elemene.
Our data provides the first evidence that β-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis. A combination of β-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer.
Gastric cancer is one of the top three leading causes of cancer death in China. Most patients present with advanced disease which limits their surgical options. Chemotherapy is thus the major treatment for advanced gastric cancer, but the outcome is still very poor, with a median overall survival time of less than 1 year [1]. Combined chemotherapy with cytotoxic drugs usually leads to severe toxicity which lowers the quality of life of patients. Thus, new agents with high anti-tumor activity but low side effects are urgently needed.
Elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane) is a novel lipid-soluble anticancer drug extracted from the traditional Chinese medicinal herb Rhizoma zedoariae [2]. β-Elemene, the active component of elemene, has been shown to be effective against various tumors such as lung cancer, colorectal cancer and glioblastoma [3–5]. In China, β-elemene has been used to effectively treat certain types of tumors in the clinic, and it presents fewer side effects than other cytotoxic agents [6, 7]. However, the mechanisms by which β-elemene kills cancer cells are still not clear. Recent studies showed that β-elemene inhibited cell proliferation by inducing apoptosis as well as cell cycle arrest [3, 8]. Others reported that the apoptosis triggered by β-elemene was through the mitochondrial-mediated pathway, as it was accompanied by a reduction of Bcl-2, Bcl-X(L) and XIAP [4, 9]. Yet the exact mechanisms still need to be further elucidated.
Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome [10]. Under normal conditions, autophagy is a mechanism for the turnover of proteins and elimination of damaged organelles to maintain cell homeostasis [11]. It starts with the formation of double membrane vesicles (autophagosomes) which engulf organelles or long-lived proteins. The autophagosomes then fuse with lysosomes, forming the autophagolysosome, in which the contents are degraded [10, 11]. It has been suggested that autophagy induced under pathological conditions functions as an adaptive cell response, allowing the cell to survive bioenergetic stress [12]. However, extensive or persistent autophagy also results in cell death [13]. Thus, autophagy is an important and decisive factor in the balance between cell death and survival.
Recent studies have shown that some chemotherapeutics known to activate apoptosis also induce autophagy [14]. Inhibition of autophagy by pharmacological inhibitors can enhance the anti-tumor activity of cytotoxic agents [15, 16]. In these cases, autophagy serves as a protector - it prevents cells from undergoing apoptosis. However, autophagy can also do the opposite; it can kill cells by inducing autophagic cell death [17, 18]. The molecular mechanisms by which autophagy regulates survival and death need to be further studied.
In the present study, we report that β-elemene induces apoptosis as well as protective autophagy in human gastric cancer cells. Induction of autophagy was associated with inhibition of the PI3K/Akt/mTOR signaling pathway, and inhibition of autophagy could enhance β-elemene-induced apoptosis.
Cell cultures
The human gastric cancer cells MGC803 and SGC7901 were obtained from the Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China). The cells were cultured in RPMI-1640 medium (Gibco) containing 10% heat-inactivated fetal bovine serum (FBS), penicillin (100 U/mL) and streptomycin (100 mg/mL) at 37°C under an atmosphere of 95% air and 5% CO2. The cells were routinely subcultured every 2-3 days, and were all from the logarithmic phase of growth.
Reagents and antibodies
β-Elemene was obtained from Yuanda Pharmaceuticals (Dalian, China). 3-Methyladenine (3-MA) and chlorochine (CQ) were purchased from Sigma-Aldrich (St. Louis, Mo. USA). LysoTracker and Hoechst33342 were from Invitrogen (USA). Anti-Bcl-2, anti-Bax, anti-Survivin, anti-actin and anti-Akt antibodies were purchased from Santa Cruz Biotechnology (USA). Anti-LC3, anti-Beclin 1, anti-Atg5, anti-Atg9 and anti-Atg16L antibodies were from Novus Biological (Littleton, CO, USA). Anti-caspase 3, anti-poly(ADP-ribose) polymerase (PARP), anti-phospho-Akt (Ser-473), anti-phospho-mTOR, anti-mTOR, anti-phospho-p70S6K1, and anti-p70S6K1 antibodies were purchased from Cell Signaling Technology (USA).
Cell viability assay
Cell viability was measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The cells were seeded at 5 × 104 cells/well in 96-well plates, incubated overnight and then exposed to the indicated concentrations of β-elemene for the indicated times. Thereafter, 20 μl of MTT solution (5 mg/mL) was added to each well, and the cells were incubated for another 4 h at 37°C. After removal of the culture medium, the cells were lysed in 200 μl of dimethylsulfoxide (DMSO), and the optical density (OD) was measured at 570 nm with a microplate reader (Model 550; Bio-Rad Laboratories, USA). The following formula was used: cell viability = (OD of the experimental sample/OD of the control group) × 100%.
Analysis of apoptosis
Cells were seeded at 3 × 105 cells/well in 6-well plates, incubated overnight and then exposed to the indicated concentrations of β-elemene for the indicated times. Cells were collected and incubated with 1 μg/mL Annexin V for 20 min in the dark. Finally, the samples were evaluated by flow cytometry and the data were analyzed using WinMDI software.
For the analysis of green fluorescent protein-fused LC3 (GFP -LC3) localization, MGC 803 cells were transfected with a plasmid encoding GFP-LC3 (kindly provided by Høyer-Hansen M, Danish Cancer Society) and stably expressing cells were selected with changes of media containing 200 μg/mL of G418. Transfection was performed using Lipofectamine 2000 reagent (Invitrogen, USA), according to the manufacturer's instructions. After treatment of 10 or 50 μg/mL β-elemene for 24 h, cells were incubated with 50 nmol/L LysoTracker for 30 min at room temperature, and the nucleus was stained with Hoechst33342. The images were obtained with a fluorescence microscope (Olympus, Japan). The detection of punctated GFP-LC3 co-locolized with LysoTracker indicated the formation of autophagosomes.
Transmission electron microscopy
Cells were treated and collected by trypsinization, then fixed with 2.5% phosphate-buffered gluteraldehyde, postfixed in 1% phosphate-buffered osmium tetroxide. Cells were then embedded, sectioned, double stained with uranyl acetate and lead citrate, and analyzed using a JEM-1200EX transmission electron microscope (JEOL, Japan).
Cells were washed twice with ice-cold PBS and solubilized in 1% Triton lysis buffer [1% Triton X-100, 50 mmol/L Tris-Cl (pH 7.4), 150 mmol/L NaCl, 10 mmol/L EDTA, 100 mmol/L NaF, 1 mmol/L Na3VO4, 1 mmol/L PMSF and 2 μg/mL aprotinin] on ice, then quantified using the Lowry method. Cell lysate proteins (50 μg) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoretically transferred to nitrocellulose membranes (Immoblin-P; Millipore, USA). The membranes were blocked with 5% skim milk in TBST buffer [10 mmol/L Tris (pH 7.4), 150 mmol/L NaCl and 0.1% Tween-20] at room temperature for 1 h and incubated overnight at 4°C with the indicated primary antibodies. After the membranes were washed with TBST buffer, they were reacted with the appropriate horseradish peroxidase-conjugated secondary antibodies for 30 min at room temperature. After extensive washing with TBST buffer, the proteins were visualized with enhanced chemiluminescence reagent (SuperSignal Western Pico Chemiluminescent Substrate; Pierce, Rockford, IL, USA). The images were analyzed using NIH Image J software.
Clonogenic assay
Cells were seeded at 5 × 104cells/well in 12-well plates and treated with either 50 μg/mL β-elemene or 20 μmol/L CQ, or co-treatment with β-elemene and CQ for 6 h. Cells were then plated (in triplicate) at 200 cells per well into 12-well plates with fresh drug-free medium. Cells were incubated for an additional 14 days, and the clones in each well were stained, counted and photographed.
Small interfering RNA corresponding to the human Beclin 1 cDNA sequence (5'-CAGTTTGGCACAATCAATAtt-3') [19] and a control siRNA (5'-UUCUCCGAACGUGUCACGUtt-3') were from Genechem Co. (Shanghai, China). Cells were transfected with either Beclin 1 siRNA or control siRNA at 100 nmol/L using DharmaFECT transfection agent (Dharmacon Research, CO, USA) according to the manufacturer's guidelines. Forty-eight hours after transfection, the cells were subcultured for further use. The expression of Beclin 1 was verified by western blotting.
The experiments were repeated at least three times. Data are expressed as the means ± SD. Differences in the results for two groups were evaluated by the Student's t-test. P < 0.05 was considered to be statistically significant.
β-Elemene inhibited cell viability and induced apoptosis
Human gastric cancer MGC803 cells were treated with β-elemene at concentrations ranging from 10 μg/mL to 200 μg/mL for 24, 48 or 72 h. Cell viability assays showed that β-elemene inhibited cell growth in a dose-dependent manner (Figure 1A). The IC50 values of β-elemene at 24, 48 and 72 h were 80.03 μg/mL, 56.03 μg/mL and 45.05 μg/mL, respectively. Flow cytometry assays showed a significant increase in the apoptotic population among the cells treated with β-elemene at 24 h (Figure 1B). To further confirm that apoptosis was induced by β-elemene, western blotting was performed to detect the cleavage of caspase 3 as well as PARP. As shown in Figure 1C β-elemene clearly cleaved pro-caspase 3 and PARP to their active forms. The effects of β-elemene on the expression of apoptosis associated proteins were further investigated. Western blotting showed that β-elemene had little effect on the expression of Bax or Bcl-2, but significantly down-regulated the level of Survivin (Figure 1D and 1E). These data indicated that β-elemene inhibits cell viability through inducing apoptosis in human gastric cancer cells.
Effects of β-elemene on cell viability and apoptosis of MGC803 cells. (A) MGC803 cells were treated with β-elemene at the indicated concentrations for 24, 48 or 72 h, and the cell viability was analyzed by MTT assay. Dots: mean of three independent experiments; bars: SD. (B) MGC803 cells were treated with 10, 50 and 200 μg/mL β-elemene for 24 h, and apoptosis was determined by flow cytometry followed by Annexin V staining. (C) Cells were treated with either 10 or 50 μg/mL β-elemene for 24 h, and the cleavage of caspase 3 and PARP was detected by western blotting. (D) Cells were treated as described above, and the expression of Bcl-2, Bax and Survivin was detected by western blotting. The results were representatives of three independent experiments. Actin was used as loading control. (E) The levels of Bcl-2, Bax and Survivin were measured by NIH Image J software and corrected for actin. Columns: mean of three independent experiments; bars: SD. * P<0.05 vs. untreated control.
β-Elemene induced autophagosome formation
It has been reported that some lipid-soluble anti-tumor agents such as oleandrin could simultaneously induce apoptosis and autophagy [20], so we asked if there was any autophagy in the cells treated with β-elemene. MGC803 cells stably expressing GFP-LC3 were treated with 10 or 50 μg/mL β-elemene for 24 h, and the localization of GFP-LC3 was evaluated under fluorescent microscopy. As shown in Figure 2A, only a few LC3-positive puncta were observed in untreated control cells. However, in the cells treated with 10 μg/mL β-elemene, over 30% of cells were observed with LC3-positive puncta, and in the cells treated with 50 μg/mL β-elemene, more than 90% of cells showed LC3-positive puncta. GFP-LC3 co-localized with LysoTracker after treatment with β-elemene, which suggests the accumulation of autophagosomes. The formation of autophagosomes was further confirmed by transmission electron microscopy. Upon treatment of 50 μg/mL β-elemene many autophagic vesicles, double membrane enclosed vesicle containing engulfed organelles, were observed in the cytoplasm (Figure 2B). Meanwhile, β-elemene treatment also significantly increased LC3-II levels as demonstrated by western blotting (Figure 2C). These data indicate that β-elemene treatment not only results in apoptosis, but also induces autophagy.
β-Elemene induced autophagy in MGC803 cells. (A) MGC803 cells stably expressing GFP-LC3 were treated with either 10 or 50 μg/mL β-elemene for 24 h, stained and observed under a fluorescence microscope as described in Materials and Methods. The percentage of cells with punctuate dots was represented with a histogram. Columns; mean of three independent experiments, bars: SD. (B) Cells were treated with 50 μg/mL β-elemene for 24 h, then harvested and subjected to transmission electron microscopy as described in Materials and Methods. (C) After the cells were exposed to 10 or 50 μg/mL β-elemene for 24 h, cell lysates were subjected to western blotting with an anti-LC3 antibody. The results were representatives of three independent experiments. Actin was used as loading control.
Effects of β-elemene on autophagy-associated proteins
Autophagy is regulated by a group of proteins called Atg (autophagy-related) proteins [10]. Some stimuli can modulate autophagy simply by changing the expression of certain Atg protein [21]. To determine if β-elemene could affect the expression of Atg proteins, MGC803 cells were treated with 50 μg/mL β-elemene for 24 h and the levels of some Atg proteins were detected by western blotting. After treatment with β-elemene, the level of Atg5-Atg12 conjugated protein was up-regulated, whereas the expression of Beclin1, Atg5, Atg9 and Atg16L was not affected significantly (Figure 3A and 3B). These data suggest that the up-regulation of Atg5-Atg12 conjugated protein might contribute to the induction of autophagy by β-elemene.
Effect of β-elemene on the expression of autophagy-related proteins. (A) After the cells were exposed to 10 or 50 μg/mL β-elemene for 24 h, cell lysates were subjected to western blotting with specific antibodies. The results were representatives of three independent experiments. Actin was used as loading control. (B) The levels of Atg proteins were measured by NIH Image J software and corrected for actin. Columns; mean of three independent experiments, bars: SD. * P<0.05 vs. untreated control.
β-elemene inhibited PI3K/Akt/mTOR signalling pathway
It has been well documented that the PI3K/Akt/mTOR/p70S6K1 signalling pathway plays a key role in regulating both apoptosis and autophagy, so the effects of β-elemene on the activity of this pathway were studied next. Cells were treated with 10 or 50 μg/mL β-elemene for 24 h, and the levels of phospho-Akt, phospho-mTOR and phospho-p70S6K1 were detected by western blotting. After treatment with 50 μg/mL β-elemene, the level of phospho-Akt was obviously down-regulated, leading to the down-regulation of downstream phospho-mTOR as well as phospho-p70S6K1 (Figure 4A). A low dose (10 μg/mL) of β-elemene had little effect on PI3K/Akt/mTOR/p70S6K1 activity. Interestingly, a transient activation of PI3K/Akt/mTOR/p70S6K1 was observed after the cells were exposed to β-elemene for short times. As shown in Figure 4B, the level of phospho-Akt increased after 4 h, stayed active until 8 h, and went down after 16 h. Similar changes were observed on the phosphorylation of mTOR and p70S6K1. The cleavage of PARP and conversion of LC3 I to LC3 II was also seen following treatment with 50 μg/mL β-elemene at 16 h and 24 h, consistent with the change of PI3K/Akt/mTOR/p70S6K1 activity (Figure 4C). These data indicated that β-elemene induced apoptosis and autophagy might be due to its inhibition of the PI3K/Akt/mTOR/p70S6K1 signalling pathway.
Effect of β-elemene on the PI3K/Akt/mTOR/p70S6K1 signalling pathway. (A) MGC803 cells were exposed to 10 or 50 μg/mL β-elemene for 24 h, and the expression of phospho-Akt, phospho-mTOR and phospho-p70S6K1 was detected by western blotting. (B) and (C) Cells were treated with 50 μg/mL β-elemene for the indicated times, and cell lysates were subjected to western blotting with specific antibodies. The results were representatives of three independent experiments. Actin was used as loading control.
β-Elemene-induced autophagy protected MGC803 cells from undergoing apoptosis
Since autophagy can result in both survival and cell death, we then asked whether β-elemene-induced autophagy is protective or pro-apoptotic. MGC803 cells were treated with either 50 μg/mL β-elemene or 20 μmol/L CQ (an inhibitor of autophagy which blocks the fusion of autophagosomes with lysosomes, stopping autophagy at the late phase), or co-treated with β-elemene and CQ for 24 h. Cell viability assays showed that co-treatment with β-elemene and CQ significantly decreased cell viability, compared with the cells treated with β-elemene alone (48.50 ± 5.07% vs. 78.27 ± 1.57%, P<0.05) (Figure 5A). Co-treatment with β-elemene and CQ also significantly reduced the clone formation ability of the cells and increased the apoptotic population compared with the cells treated with β-elemene alone (Figure 5B and 5C). To confirm the effect of autophagy inhibition by the pharmacologic agent CQ on β-elemene-induced apoptosis, an RNA interference approach was used to knock down the expression of Beclin 1. Figure 5D shows that the level of Beclin 1 was significantly decreased in Beclin 1 siRNA-treated cells. Compared with the results in siRNA controls, knockdown of Beclin 1 decreased significantly the cell viability, and enhanced β-elemene-induced apoptosis (Figure 5 E and 5F). These data indicate that blockage of autophagy enhanced the antitumor effect of β-elemene in MGC803 cells.
Inhibition of autophagy enhanced the anti-tumor effect of β-elemene on MGC803 cells. (A) MGC803 cells were exposed to either 50 μg/mL β-elemene or 20 μmol/L CQ, or a combined treatment of β-elemene and CQ for 24 h, and cell viability was measured by MTT assay. (B) Cells were treated with 50 μg/mL β-elemene or 20 μmol/L CQ, or a combined treatment of β-elemene and CQ for 6 h, and the clone formation ability was analyzed. Columns: mean of three independent experiments; bars: SD. * P<0.05 vs. cells treated with β-elemene alone. (C) Cells were treated as described in A and apoptosis was analyzed by flow cytometry following Annexin V staning. (D) Cells were transfected with either Beclin1 siRNA or a non-target control siRNA for 48 h, and the expression of Beclin 1 was verified by western blotting. (E) and (F) Forty-eight hours after transfection, the cells were treated with 50 μg/mL β-elemene for another 24 h, and cell viability (E) and apoptosis (F) were analyzed. * P<0.05 vs. cells transfected with control siRNA.
β-Elemene induced protective autophagy in SGC7901 gastric cancer cells
To prove that the apoptosis and autophagy induced by β-elemene is not cell-specific, we examined the antitumor effect of β-elemene on another human gastric cancer cell line, SGC7901. We found that β-elemene inhibited the viability of SGC7901 cells in a dose-dependent manner, and the IC50 values at 24, 48 and 72 h were 89.68 μg/mL, 75.88 μg/mL and 67.13 μg/mL, respectively (Figure 6A). β-Elemene inhibited mTOR activity and induced apoptosis and autophagy, which were evidenced by the cleavage of PARP and the conversion of LC3-I to LC3-II (Figure 6B). The contribution of autophagy to β-elemene-induced apoptosis in SGC7901 cells was evaluated further by co-treating the cells with β-elemene and the autophagy inhibitor, 3-MA or CQ. Compared with the cells treated with β-elemene alone, co-treatment with β-elemene and 3-MA or CQ reduced significantly the viability and clone formation ability of the cells, and increased the apoptotic population (Figure 6C, D and 6E). Similar results from these two human gastric cancer lines indicate that autophagy induced by β-elemene served in a protective manner, and blockage of autophagy enhanced the anti-tumor effect of β-elemene in human gastric cancer cells.
Anti-tumor effect of β-elemene on SGC7901 gastric cancer cells. (A) SGC7901 cells were treated with β-elemene at the indicated concentrations for 24, 48 or 72 h, and the cell viability was analyzed by the MTT assay. Dots: mean of three independent experiments; bars: SD. (B) Cells were treated with 20 or 100 μg/mL β-elemene for 24 h, and cell lysates were subjected to western blotting with specific antibodies. (C) Cells were exposed to either 100 μg/mL β-elemene, 10 mmol/L 3-MA, 20 μmol/L CQ, or a combined treatment of β-elemene and 3-MA or CQ for 24 h, and cell viability was measured by the MTT assay. (D) Cells were treated with 100 μg/mL β-elemene, 10 mmol/L 3-MA, 20 μmol/L CQ, or a combined treatment of β-elemene and 3-MA or CQ for 6 h, and the clone formation ability was analyzed. Columns: mean of three independent experiments; bars: SD. * P<0.05 vs. cells treated with β-elemene alone. (E) Cells were treated as described in A and apoptosis was analyzed by flow cytometry following Annexin V staning.
Recently, some traditional Chinese medicines have exhibited promising anti-tumor activity. β-Elemene as a novel anti-cancer herbal medicine has shown broad anti-tumor effects in vitro and in vivo [2–5]. It has been approved by the State Food and Drug Administration of China for the treatment of malignant effusion and some solid tumors. However, the effects of β-elemene on gastric cancer cells have not been documented. In the present study, we provide the first evidence that β-elemene could inhibit the proliferation of human gastric cancer cells.
Previous study showed that β-elemene induced both G2/M phase arrest and apoptotic cell death in non-small cell lung cancer cells [3]; whereas in ovarian carcinoma cells it only induced cell cycle arrest at G2/M phase [8]. In the present study β-elemene induced obvious apoptosis in gastric cancer cells, but had little effect on cell cycle distribution. This may be due to the different regulating mechanism of cell cycle progress in different types of tumor cells.
Meanwhile, in our study a robust autophagy was observed among the cells treated with β-elemene, which was shown by the increase of punctate LC3 and the morphologic changes. Western blotting also showed a conversion of LC3-I to LC3-II. These specific changes of LC3 have been characterized as an autophagosomal marker in mammalian autophagy. This is the first demonstration that β-elemene could induce autophagy. It has been demonstrated that autophagy is activated by some anti-tumor drugs while they induce apoptosis [14–16]. The autophagy induced by these agents leads to either survival or autophagic cell death. Whether β-elemene-induced autophagy is a protective or a deadly response was confirmed later.
Although the detailed mechanisms regulating autophagy have not been well documented, just like for apoptosis, the process of autophagy is controlled under a group of evolutionarily conserved proteins, the Atg proteins [10]. Accumulated evidence suggest that the induction of autophagy is associated with the up-regulation of certain Atg proteins [21–23]. Thyagarajan et al. reported that triterpenes-induced autophagy is accompanied by the up-regulation of Beclin 1 [21]. Others reported that increased transcription of Atg5 can lead to autophagy [23]. In the present study β-elemene induced autophagy without alternating significantly the levels of Beclin 1, Atg5, Atg9 or Atg16L, while the expression of the Atg5-Atg12 conjugated protein was up-regulated significantly. This is similar to the results reported by Kim et al that irradiation up-regulated Atg5-Atg12 and activated autophagy [24]. Along with the conversion of LC3, the changes of these molecular markers finally lead to autophagy.
The PI3K/Akt pathway has been reported to play an important role in the inhibition of apoptosis [25–28]. Once activated, Akt phosphorylates downstream mTOR, leading to the phospharylation of its target p70S6K1, which promotes cell growth and inhibits apoptosis [29]. Moreover, recent studies have suggested that Survivin is positively regulated by the PI3K/Akt/p70S6K1 pathway [30]. In our study β-elemene inhibited the phospharylation of Akt, mTOR, and p70S6K1, and down-regulated the expression of Survivin but not other apoptotic proteins. This indicated that inhibition of PI3K/Akt/mTOR/p70S6K1 and Survivin by β-elemene might lead to the induction of apoptosis. Meanwhile, mTOR is also a key regulator of autophagy, and inhibition of mTOR activity by some agents has been reported to activate autophagy [31–33]. This may explain the phenomenon of autophagy among the cells treated with β-elemene in the present study.
Since autophagy can result in both survival and cell death, we then investigated whether the autophagy induced by β-elemene was a protective response or a process leading to death. We found that inhibition of autophagy by the autophagy inhibitor, or by genetic knockdown of Beclin 1, the Atg protein essential for autophagy initiation, enhanced significantly the antitumor effect of β-elemene. This phenomenon was also seen in another gastric cancer cell line, SGC7901. These data suggest that the inhibition of PI3K/Akt/mTOR activity by β-elemene resulted in two opposite consequences: on the one hand, it inhibited cell viability and induced apoptosis, which led to death; on the other hand, it activated a protective autophagy to adapt to the stressful conditions and protect cells from death. Inhibition of protective autophagy might be a good way to enhance the anti-tumor effect of β-elemene.
Taken together, our study provides the first evidence that β-elemene can inhibit the proliferation of human gastric cancer cells by inducing apoptosis. The anti-cancer effect of β-elemene was associated with inhibition of the PI3K/Akt/mTOR/p70S6K1 signaling pathway, which also led to the activation of a protective autophagy. Inhibition of autophagy significantly enhanced the apoptosis-inducing ability, which suggests that the combination of β-elemene with an autophagy inhibitor might be useful for the treatment of advanced gastric cancer.
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Kennedy SG, Wagner AJ, Conzen SD, Jordán J, Bellacosa A, Tsichlis PN, Hay N: The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev. 1997, 11: 701-713. 10.1101/gad.11.6.701.
Qu X, Zhang Y, Li Y, Hu X, Xu Y, Xu L, Hou K, Sada K, Liu Y: Ubiquitin ligase Cbl-b sensitizes leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial pathway and modulating Akt and ERK survival signals. FEBS Lett. 2009, 583: 2255-2262. 10.1016/j.febslet.2009.05.054.
Qu JL, Qu XJ, Zhao MF, Teng YE, Zhang Y, Hou KZ, Jiang YH, Yang XH, Liu YP: Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig Liver Dis. 2009, 41: 875-880. 10.1016/j.dld.2009.04.006.
Qu X, Li Y, Liu J, Xu L, Zhang Y, Hu X, Hou K, Liu Y: Cbl-b promotes chemotherapy-induced apoptosis in rat basophilic leukemia cells by suppressing PI3K/Akt activation and enhancing MEK/ERK activation. Mol Cell Biochem. 2010, 340: 107-114. 10.1007/s11010-010-0407-8.
Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C: PI3K/Akt and apoptosis: size matters. Oncogene. 2003, 22: 8983-8998. 10.1038/sj.onc.1207115.
Zhao P, Meng Q, Liu LZ, You YP, Liu N, Jiang BH: Regulation of survivin by PI3K/Akt/p70S6K1 pathway. Biochem Biophys Res Commun. 2010, 395: 219-224. 10.1016/j.bbrc.2010.03.165.
Jung CH, Ro SH, Cao J, Otto NM, Kim DH: mTOR regulation of autophagy. FEBS Lett. 2010, 584: 1287-1295. 10.1016/j.febslet.2010.01.017.
Nakatsu Y, Kotake Y, Takai N, Ohta S: Involvement of autophagy via mammalian target of rapamycin (mTOR) inhibition in tributyltin-induced neuronal cell death. J Toxicol Sci. 2010, 35: 245-251. 10.2131/jts.35.245.
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We thank Dr. Høyer-Hansen M (Danish Cancer Society, Denmark) for providing the GFP-LC3 plasmid.
Financial support: YL (Chinese National Foundation of National Sciences grants 30770993); XQ (China Postdoctor Foundation of Science grants 20070411081); JL (Fund for Scientific Research of The First Hospital of China Medical University, fsfh1002); YZ (The Doctor Startup Fund Program Funded by CSCO-King Kong Elemene).
Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, P.R. China
Jing Liu, Ye Zhang, Jinglei Qu, Ling Xu, Kezuo Hou, Jingdong Zhang, Xiujuan Qu & Yunpeng Liu
Ye Zhang
Jinglei Qu
Ling Xu
Kezuo Hou
Jingdong Zhang
Xiujuan Qu
Yunpeng Liu
Correspondence to Xiujuan Qu or Yunpeng Liu.
JL carried out the cellular and biochemistry study, participated in the transfection and drafted the manuscript. YZ and LX carried out the transfection and participated in fluorescence microscopy assays. JQ and KH carried out the transmission electron microscopy assays. JZ participated in the biochemistry study. XQ and YL conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
Liu, J., Zhang, Y., Qu, J. et al. β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis. BMC Cancer 11, 183 (2011). https://doi.org/10.1186/1471-2407-11-183
Gastric Cancer Cell
Advanced Gastric Cancer
Human Gastric Cancer
SGC7901 Cell


Board-certified orthodontists are uniquely qualified to provide top-quality orthodontic care. Orthodontists complete additional training in a dental college after graduating from dental school with a general dentistry degree. Another name for an Orthodontist is a Dentofacial Orthodontic. They really are some of the reasons why you should see an orthodontist.
With the advanced technology today, there are many effective treatments that can be done to get rid of any dental problem within a short period. For people who need braces but hate the idea of ugly, uncomfortable metal braces, Invisalign offers a superb solution. Invisalign aligners are almost invisible and easily removable. In Invisalign treatment 3D, set of aligners are produced accordingly when the imaging technology is used where virtual image is generated to the teeth.
Patients can become transfer cases if they neglect to get needed orthodontic care. There has been a lot of competition for patients between orthodontists and general dentists in recent years. However, patients receive markedly different treatment from orthodontists and general dentists, according to studies. It is important to research how much braces cost in Grove City.
Anyone who wishes to become an orthodontist must first get a dental degree and afterwards serve a 2-3 year residency at an American Dental Association-approved university medical facility. While a resident, a prospective orthodontist must pass clinical and written examinations to receive his or her American Board of Orthodontics certification. The American Dental Association only approves of that path for the orthodontic specialty.
You should see the orthodontist once or twice, because their strategies are dependent on checkups. Diagnoses of alignment problems can be made either by X-ray scans or through bitable molds. Braces, Invisalign retainers, and head gear are just a few of the devices used by orthodontists. If the problem is persistent, cracking or wiring the jaw could be necessary.
Another important thing to think about in having the latest technology in clinics. The very best orthodontists will have the most modern equipment and updated facilities because they invest in quality. Reliable orthodontists use the latest technology for braces and wires, technology that can accelerate the treatment process.
Other techniques which are complex can be used by dentists to give help as an alternative to metal braces. People with poorly aligned teeth are currently in a position to get them straightened without the discomfort and unsightliness of metal braces. Only orthodontists have the specialized training to apply and make regular adjustment to metal braces. Treatments like Invisalign can only be performed by certified orthodontists.


text:
Biosynthetic® Technologies Commercializes Its First in Class High-Performing Biobased Synthetic Motor Oil Using High-Oleic Soybean Oil from Soybeans Grown by U.S. Farmers.
Biosynthetic Technologies
INDIANAPOLIS, Oct. 25, 2019 /PRNewswire/ -- Biosynthetic® Technologies today announced the commercial availability of a high-performing biobased synthetic motor oil using high-oleic soybean oil from soybeans grown by U.S. farmers. The Department of Defense and Washington, D.C. area fleet demonstrations found the product meets or exceeds their performance requirements. Biosynthetic® Technologies' motor oil is also recognized as a United States Department of Agriculture (USDA) Certified Biobased Product meeting the federally mandated purchasing initiative known as the "BioPreferred Program."
As of today Biosynthetic® fully synthetic motor oil, 5W20 and 5W30 is available for purchase on www.biosynthetic.com and www.amazon.com.
The United Soybean Board (USB) and U.S. Department of Agriculture (USDA) have supported the soy-based, drop-in, synthetic alternative to petroleum-based motor oil. The biobased alternative is well suited for high-temperature automotive and industrial applications. USB introduced the product to multiple Washington, D.C. region fleets, including DC Water that field tested the motor oil. DC Water concluded the test to be successful with the biobased motor oil, demonstrating strong performance, improved fuel efficiency, and cleaner engines when compared to the petroleum-based oil they had previously used. The Smithsonian Institution, Arlington County, Va., and Prince George's County, Md. also reported success with the biobased motor oil after participating in a trial.
"At DC Water, we are always looking for innovative options that can help improve the sustainability of our fleet without sacrificing performance or increasing costs," said Tim Fitzgerald, director of fleet management for DC Water. "This biobased motor oil exceeded our expectations in terms of performance and engine cleanliness. The oil samples have shown increased longevity and stability over time, while the equipment appears to be cleaner, which is a definite plus for us. The oil is less harmful to the environment and I see real potential for greater use of this biobased alternative in the future."
The Defense Logistics Agency (DLA) Aviation in coordination with the Air Force and the Office of the Assistant Secretary of Defense for Sustainment conducted an 18-month limited field demonstration project to evaluate synthetic biobased motor oil in non-tactical Department of Defense and federal agency vehicles with gasoline-powered engines. The effort included analysis of oil samples. It concluded: "The demonstrated biobased full synthetic motor oils were found to meet or exceed the DoD and federal agencies performance requirements."
Participants In the demonstration Included:
Air Force Bases: Fairchild; Luke; Malstrom, and Seymour Johnson
Army: Fort Irwin
Navy: Naval Air Station Lemoore
Department of Homeland Security: Federal Law Enforcement Training Center
National Aeronautics and Space Administration: Kennedy Space Center; Langley Research Center; Armstrong Flight Research Center, and White Sands Test Facility
The USAF 441st Vehicle Support Chain Operations Squadron provided access to Air Force Vehicles in various climates.
"Through the soybean checkoff, U.S. soybean growers have supported the innovation of both high-oleic soybeans as well as this motor oil made with them," said USB Director Greg Fujan, a soybean grower from Weston, Neb. "USB investments contributed to these results that increase demand for U.S. soybeans while offering a new high-performing American-made motor oil for millions of vehicles."
"We are extremely proud to launch our new line of high-performance motor oils manufactured with high-oleic soybean oil from soybeans grown by U.S. farmers. Our motor oils are certified by the American Petroleum Institute (API) and not only do they reduce sludge and varnish, they improve fuel economy and provide environmental benefits for renewability and biodegradability as well," says Mark Miller, CEO at Biosynthetic® Technologies. "Our revolutionary new class of biodegradable synthetic base oils have enabled us to commercialize an automotive engine oil that is sustainable while delivering the highest levels of performance, giving creed to our vision of DELIVERING INNOVATIONS FOR A SUSTAINABLE FUTURE!"
About Biosynthetic® Technologies:
Biosynthetic® Technologies manufactures a revolutionary new class of biobased synthetic compounds called Estolides that are made from organic fatty acids found in various bio-derived oils. These highly functional biosynthetic oils have numerous uses in lubricant, automotive, marine, pharma and personal care applications and can be used as the primary base oil of a formulation, a component of a base oil co-blend, or even as an additive. In addition to their high-performance properties, these renewable oils are biodegradable and nontoxic. Biosynthetic® Technologies strives to make their mark on the world by delivering innovations for a sustainable future. For more information about Biosynthetic® Technologies, please visit www.biosynthetic.com and follow us on LinkedIn and Twitter.
About USB:
Because of the potential for biobased products to create new markets for soybeans, U.S. soybean farmers have invested millions of dollars to research, test and promote biobased products. Much of this work was done through the United Soybean Board, which is composed of 73 U.S. soybean farmers appointed by the U.S. Secretary of Agriculture to invest soybean checkoff funds. As stipulated in the Soybean Promotion, Research and Consumer Information Act, USDA's Agricultural Marketing Services has oversight responsibilities for the soybean checkoff.
SOURCE Biosynthetic Technologies
BIOSYNTHETIC® TECHNOLOGIES WINS THE COSMETICS & TOILETRIES (C&T) ALLĒ AWARDS FOR THE BIOESTOLIDE 250 IN THE BASE INGREDIENT CATEGORY.

redpajama_set_name: RedPajamaCommonCrawl


The beginning of another school year can be very exciting because there are many things that are "new." We may experience a new teacher, new students, new friends, new clothes, new school supplies, new bulletin boards, and more. As we launch ourselves into a new school year at the DMA, we also launch a new blog series called Teaching for Creativity. The inspiration for this new series comes from various sources, including the DMA's Center for Creative Connections; our collaborative work with UT Dallas professor and creativity specialist, Dr. Magdalena Grohman; and the 2011 Summer Seminar: Teaching for Creativity, a professional development experience for K-12 educators.
highlight creative beings from the past and present who may offer us new ways to look at the world.
For this inaugural post, I am excited to introduce you to Shadan Price. Shadan teaches art to students ages 3-5 at El Dorado Montessori in Frisco, Texas and joined us in June for the 2011 Summer Seminar. Shadan shares with us the lesson plan that she developed during the Seminar and the results of trying it out in her classroom.
During the Teaching for Creativity seminar I attended, our goal was to create a lesson plan that focused on creative thinking. The lesson I came up with did that but was also simple enough for the young children that I teach to understand. In summary, my lesson had them discussing how certain shapes (we focused on circles, squares, triangles, and rectangles) and how they are used in artwork and the real world. We looked at a few art images (ex: Van Gogh's "Starry Night", Klimt's "The Kiss") and the students pointed out those shapes in the images. We then looked at images of everyday objects (ex: buttons, tables, pizzas, etc.) and the students talked about what shapes those were. The next step was brainstorming. For each shape the class thought of objects that those particular shapes could be. This was really fun for them! I didn't want them to brainstorm for too long though because I wanted them to still have a few more ideas for the next part of the lesson which was to draw each shape on a piece of paper and then create an object (real or imaginary) out of that shape. I didn't put any restrictions on what they could draw. I just told them no matter what it was, even if it wasn't a real thing, they had to explain to me what the drawing was. For the most part the students really enjoyed this but I could immediately tell which students were not really comfortable making something completely out of their imaginations as opposed to something a little more guided. This was a good project to see who I need to work with more on their creative-thinking skills. Overall this was a good project. The students loved brainstorming and drawing their own creations!
TRIANGLE – almost all the students chose a slice of pizza….if I did this project over again I might tell them not to do that so I could see what else they came up with. A few others were roofs, mountains, cat ears, and noses.
SQUARE – iron man, robot, mirror, window, bubble machine, cage, bookshelf, frame, butterflies, purses, books, and dinosaurs.
CIRCLE – vacuum, wheels, monkey, balls, DVDs, cookies, lollipops, a "purse maker", pancakes, rings, and buttons.
RECTANGLE – monster, table, frame, door, fluorescent lights, microwave, baskets, rocketships, and sharks.
I want to express great thanks to Shadan for sharing her lesson with us. Follow this link to download the lesson: SHADAN_CREATIVE_LESSON.
What creative experiences are happening in your learning environment? Share them here and look forward to the next Teaching for Creativity post in September.
I'm excited about this new feature you are starting! Great idea!
Thanks Christine! Send us any ideas you have for nurturing creativity. Maybe we can come visit your classroom too and feature it in an upcoming blog! I hope the year is off to a pleasant start.


Classic Escapes brings travelers to Tanzania to witness the migration of nearly two million animals.
Classic Escapes' 10-day Tanzania itinerary has travelers witnessing The Great Migration of nearly two million zebras and wildebeests.
The 10-Day Tanzania: Treasures of the Land of Kilimanjaro takes travelers to visit Arusha, Lake Manyara National Park, Serengeti National Park, Oldupai Gorge and the Ngorongoro Conservation Area. Highlights include game drives in Lake Manyara National Park, where travelers can spot over 350 diverse bird species and tree-climbing lions; a visit to Serengeti National Park to watch The Great Migration; a day of exploring the floor of the Ngorongoro Crater, an extinct volcano turned World Heritage site; and much more.
The guaranteed departure date of this tour is Nov. 4, 2018, although additional departure dates can be added upon request. Pricing for this itinerary begins at $3,995 pp dbl, including superior accommodations, all meals on safari in Tanzania, all wildlife viewing by land cruiser, gratuities, park entry fees and emergency evacuation insurance. Optional post-extension to Zanzibar and a hot air balloon safari excursion in Tanzania may be added for an additional price.
For more information, visit classicescapes.com.


Since its release the iPad has garnered arguments regarding whether it is primarily a device for consumption or creation. I have always believed that it is a device capable of creation. One simply needs to consider apps such as Avid Studio, DemiBooks Composer, Pages, Keynote, Minecraft Pocket Edition, Art Rage, SketchBook Pro, Comic Life and many others. These and many other apps all allow the user to tap into their talents and produce output of which they can be proud.
Of course the iPad is also a worthy consumption device. Think of FlipBoard, Reeder, Safari, Guardian Eyewitness, The Elements, Solar Walk, and any other app that allows anyone to easily explore information, imagery and data on the web or embedded within the app.
Yet, the iPad has one challenging aspect at this time… particularly for a teacher working with a class of students, each with their own iPad. Consider a teacher that simply wants to facilitate teaching and learning and does not wish to devote hours to dealing with an interface that can at times be clunky, inconsistent and simply involves too many steps to get it to work.
Which interface!? The conventional task of collecting, assessing and returning student works that were created on an iPad.
Imagine that the students have created an elegant report in Pages, a short movie in Avid Studio or a sketch in Art Rage. As a teacher you would like to assess the students' output. Ideally the teacher would like to receive all of the students' works in a setting that allows the teacher to verify all of the submissions in a single directory or folder and then to assess each item. In addition to that you require a facility that allows the students to submit their works in such a manner that one student cannot access the work of another. Some teachers are concerned that students may simply copy or mimic the work of others. Fair point.
Why? The iPad's proprietary iOS operating system does not possess a file system like the directory and file structure of Windows or the folder and file system found in the Finder of the Mac OS.
So, what are some of the stumbling blocks?
One cannot upload a file to a LMS or CMS via a conventional browser upload.
You cannot drag & drop files so as to save them to other computers, external hard drives or portable flash drives.
You are not able to export files via a simple drag & drop or automatically sync to networked servers and non-Apple cloud based file storage systems such as DropBox.
This is due to the fact that each app on the iPad manages its own files independently of all the other apps. Files are saved with the app. They are not saved to a system wide directory or folder structure. Transferring files is challenging.
Educators and other iPad users have written about this dilemma. Check out these posts and consider the steps or variety of apps that some of the authors have set out in order to establish a workflow.
The Mac Observer: File Sharing with an iPad: Ugh!
Developing Education: Dropbox & DropDav as an iPad Filesystem…Finally!
This is madness. Some of the processes described in these posts are not workflows. They are obstacle courses. There is not an elegant solution to this dilemma. The iPad does not afford a consistent approach for the transfer of files from one device to any other device whether it be an iPad, PC, Mac or server.
Let's consider some methods for transferring files from an iPad to another device. This list is not exclusive. These solutions are designed for a single user of course. The iPad does not allow for multiple users and multiple accounts.
You can transfer files via the File Sharing window within the Apps tab of this desktop application. One device at a time. That is impractical with a class of 30 or more students. The File sharing is not consistent. Some apps only allow single files, others allow you to drag folders. Some apps only allow you to transfer files created on the iPad.
This app allows for file transfer and sharing across a wireless network. One device at a time. The teacher would need to connect to each iPad wirelessly. Locate the file and copy it to their own device. There are many other apps similar to this.
A good app no doubt. One of my favourites. Yet GoodReader has a strangely complex user interface. You can link GoodReader to a Drop Box account that is shared by the students and the teacher. Students can download and upload files to DropBox via GoodReader. That works well for PDFs that are annotated within Good Reader itself or images that have been saved to the Photos app and are then accessible within Good Reader. Limited possibilities. Complex to set up. Read this post to review the steps outlined by this educator.
One possibility is DropBox however it has limitations. After a DropBox account has been established folders can be shared with others.
One can access the same files on an iPad via the DropBox app on the iPad. The user can also access those files on the iPad using applications such as QuickOffice, GoodReader, MindNode, Photogene, WhiteBoard HD and OneEdit. A number of these apps also allow you to export to DropBox as well. GoodReader allows you to establish a two-way sync with DropBox. The problem is that although students can exchange files wirelessly with their teacher all the students have access to the works of the other students.
Many apps allow you to email files to another person. Have you ever received 30 assignments from a class of students? How about 180 assignments from an entire cohort? Ridiculous. Sure, you could set up a smart mailbox that directs all of the incoming student emails to a particular folder within an email client. You could even create a shortcut to the attachments folder on your PC or Mac. This method requires discipline on the part of the students. Each submitted file needs to be logically titled so the teacher can easily identify the identity of the owner. In addition to this there are issues regarding file size limitations and the allowed server space for each email account. It is not an elegant solution.
Some apps, such as GoodReader and MindNode, allow users to transfer files wirelessly. The app allows the user to set up the iPad as a wireless server. The IP address can be shared with others and users can drag and drop files between a computer and that app on the iPad. It is not a simple or elegant solution.
There are a number of third party desktop applications that allow you to browse the apps and files on an iPad, iPhone or iPod.
Each of these applications perform a similar function. They allow you to explore the apps and their contents. Your iPad can also perform like a thumb or flash drive. In addition to accessing the contents of apps on the iPad you can also access music files, podcasts, video, playlists, contacts, notes and images. You can transfer the contents from the iPad to a computer and vice versa via a simple drag and drop. You can drag and drop folders as well.
These third party desktop applications are not perfect. Not their fault however. Dedicated Apple apps such as Pages and Keynote do not play well with these desktop solutions. They are useful solutions for an individual that wishes to gain greater access to their iPad yet the same issue applies… one device at a time. Not an entire class.
You are required to ensure that the iPad is connected to the computer using the USB Dock Connector with all but the final two of those eight methods. Each method is different. Each require mastery of a varying set of skills. Most of them are designed for a single user simply transferring files. A teacher confident with information technology would probably find it an interesting challenge however a teacher who has been handed an iPad and told to teach will be frustrated and I do not blame them. You can explore these possibilities in detail in this document.
In essence there is not a simple and seamless solution that teachers can tap into to easily collect and assess students works created on an iPad.
A school could set up a dedicated WebDAV server such as that established by Redlands College in Queensland. Shared folders on a WebDAV server may enable students to easily share files with their teachers. Not all apps on the iPad, however, allow access to a WebDAV server. The shared folder would need to ensure that is permissions settings do not allow students to access the works of other students.
Private companies are providing possible solutions. eBackpack iPad Module is one example. It is not free of course.
One can only hope that the operating system on the iPad evolves and allows this neglected aspect of its design to simply improve. Sure, one can conduct research and be quite creative on an iPad. Yet, if you have a class of students all creating projects and media I would like to take this opportunity to wish you good luck when it is time to collect, assess and return the projects.
Please share your solutions and workflows via a comment.
In the meantime you can read this iPad File Sharing document which I recently put together. It outlines in more detail some of the ideas referred to above.
You think you've got problems. Try it when the class has a communal class set of iPads and they don't retain or allow *any* personal settings such as email because they are shared around the other classes! We set up a WebDav and the kids had to enter the server address everytime I wanted something submitted. Then they had to delete the details so the kids in the next class couldn't access their files on the WebDav settings. Sheesh!
I realize it's a little idealistic but perhaps we are asking the wrong question. If we want our students to complete authentic activities for real audiences then it's doubtful the appropriate publishing forum is a private folder that only the teacher can access.
When we do need to transfer files from our iPads to the school network we use send to Dropbox to email the files to a shared folder on one of the network drives. The contents of the emails are filed according to the subject of the email. We use either the students' usernames or the activity name depending on how we want the work filed. Almost all of the creative apps have the option to email.
Thanks for writing this informative article. I appreciate the many resources you have linked to.
I agree that there is not one simple way to share iPad creations. I wrote my own blog post about one way to do it (http://edtechbaier.blogspot.com/2012/02/workflow-how-do-students-submit-ipad.html). I think your quote, "Some of the processes described in these posts are not workflows. They are obstacle courses" is very appropriate. My solution should probably called an obstacle course as well.
However, I wanted to point out one structural difference that I have been trying to focus on in solving this problem. Rather than have students send their files directly to me, I want them to post it (put it in "the cloud") somewhere and send me a link to it.
Myself and some colleagues experienced students having access to a shared Dropbox folder and messing up each others' work. If students have their own Dropbox and share a link with me, then it can still be private and protected by the student.
Here's another example: A lot of my colleagues have been using iMovie on the iPad. It is extremely difficult to get an iMovie off of an iPad in a simple way that can be submitted to a teacher. Our approach changed and we had students upload their iMovies to a shared class youtube channel. This caused problems because the teacher would forget to change the youtube password and a student who later go in and delete everyone's' work.
Our solution was to have each student create their own Youtube channel, upload videos to that, and share the link to the video. We have student submit these links using Google Forms that we create. This makes it easy to organize the links by class period, assignment, etc.
Thanks for letting me add my two cents and thanks again for sharing these resources.
We have also had trouble with iMovie.
I think your solution with individual YouTube channels and then links in a shared Google Doc is great.
The publishing process is genuine but the teacher still ends up with an easily accessible collated document.
a possible solution to all of this is Do.com ! If integrated to studentforce then files, tasks, other faculty > student and student > faculty submissions can be accomplished (including document and graphics transfers) and then associated to classes, assignments, etc.
Fantastic article. We are suffering the same fate but with one more issue, just to make it more fun.
We exist behind an authenticated and filtered firewall. The powers that be have filtered anything that is cloud based. So dropbox, sugarsync and even google docs are unavailable to our students..
Fortunately we can use the official Moodle app that allows students to upload images and videos to our Moodle. better than nothing I spose.
I have been teaching digital design (photography and Graphics for about 10 years now, each year it changes slightly and it seems we are always pushing the kids comfort level. I may get to a point where I host a blog, but for now I prefer to free solutions that exist. Last year each student maintained a blogger page those were okay, this generation was only 50% ready to undertake maintaining a blog-like portfolio, they are still new to the digital creation realm. Haven't tried blogger with an iPad… This year, and it has worked really well, we are using Tumblr, again not completely tested, but it seems like it might work. I am entertaining thoughts of hosting the entire class on an iPad. We are posting products mostly our designs and students are reflecting on their work. It is hard to begin a network of critiques, but that is next.
Another neat solution for saving files, as well as placing them on the iPad, is SugarSync. It has a great web-based interface and a teacher can easily setup a place for students to drop content there. Using multiple SugarSync accounts–one per class period–would make it possible to have a share area for each group of students.
John, thanks so much for sharing these points! I had been wondering what kind of workshop to do at an upcoming iPad session, and this would be a fun topic to explore!
Look into using SendToDropBox along with a DropBox account. It allocates an email address to a DropBox allowing users to email to a DropBox account – works pretty seamlessly. Students can then submit to your DropBox account without ever getting access to it.
The Edmodo iPad app was just updated to allow uploading of images and videos from an iPad's Photo Library to a student's Edmodo Library. Now if only Edmodo could accept other file types from iPad, it would be one of the easiest ways for students to get work to the teacher and classmates.
Thanks so much for the information shared in this post. These "workflow"issues with any new technology need to be sorted…they can make or break a teacher's willingness to have a go. Can I change the ideas around and suggest that students take responsibility for the storage and distribution of their files? If each student has their own online space..whether it be a blog, wiki, digital portfolio or evernote account etc…they can publish/store/file all their work in their "space" which can be fed back to the teachers RSS reader for viewing/assessment etc. Information can be kept private until assessed if there is a concern re authentication. Being a secondary maths/sci teacher (disclosure: not classroom teaching at the moment) I'll choose a yr 9 student to illustrate. She has her iPad and is taking a video of the chemistry experiment (app) she and her partner are doing. Notes are taken by hand in her exercise book which she scans (app) and sends to her Evernote account (app) with a few tags for easy retrieval later. When time permits she puts her report together (app), uploads it to her "online space" and I ( teacher) can have a look in my RSS reader (app). I can leave feedback and download a copy for my own files if needed. I've used the generic "app" here because we all have our own preferances, but Evernote is a must have as a student "locker" to throw everything in. Most of the apps I've been playing with save to Evernote and Dropbox. Thanks for reading my 2 cents worth…I'm keen to know what others think.
We have run into our own similar problems over the last year and a half using iPads in the elementary classroom. I think the main issue that Apple has changed in the game and that we are having difficult accepting is that the end user should be in control and not the system as a whole. As educators, we are used to a level of control with everything. The world has changed so quickly over the past few years and the control now lies in the end user's hands.
Think about it, the flipped classroom is the control of the end user. The Bring Your Own Device movement is in the hands of the end user. Apple made the iOS devices personal devices and teaching is becoming more and more personal as well. We need to focus less on the issues of how we are going to gather the information and give the students creative freedom to figure out how they are going to get it to us. We want them to learn self sufficiency, but have such a difficult time giving them the opportunity to practice what they learn. Where there's a will there's a way.
I am not preaching, because I too am guilty of these same things. However, I did see a pattern as I read this article and the feedback and wanted to make sure I pointed it out. I have plenty of experience over the last 18 months learning things the hard way, since few examples existed with iPads. I hope that we can continue to learn from each other. The end results will benefit every one of us. It's all about the kids after all.
We as teachers are using the iPad in ways it was not intended – it is a personal device and does well for what it is designed for – a personal device – not the education market – but is is great that learners have taken to it.
I agree with Lee Anne – maybe we need change in what we do – not wait for the device to change. Maybe the iPad does not suit the traditional 'hand in assignment for marking' model. It is more suited to a social model – and easy to get creative output onto the web (e.g. youtube) and maybe 'marking' or 'assessing' could be different?
We have found emailing to a blog post useful for some output from the iPad.
What a great post! I think that much of the problem discussed regarding the iPad can be avoided if we start thinking about the internet more like our students. I am a high school teacher, so my students come to me with pretty heavy internet/technology exposure and this year I have really put a heavier emphasis on the exchange of knowledge. Students demonstrating their understanding not just to me but to our entire community of learners. This involves a lot of what has already been mentioned things like edmodo, Twitter, and DropItToMe. As teachers wanting and looking for more ways to incorporate new technology and Web 2.0 tools we need to really reevaluate how we have done things in the past. I will say this year has been one of the most exciting in my teaching career and I credit a lot of that to my student's excitement comfort using the tools available to them.
Like I said, great post with some great suggestions for tools and apps that could be helpful!
February 2012 — Did you read this one?
Thousands of Chinese child slave labor workers have literally been worked to death to meet the demands for this product in the West and you think *this* is the dark side of the iPad?
This post made me sick. I'm particularly appalled that no one commenting on this has given any thought to the conditions in which this product is produced. Do you not care about the world we inhabit? There are more important things to being a human being than owning this stupid little piece of gadgetry.
Through the use of My Big Campus and a WebDAV we have solved most if not all of the issues we were facing with the "Dark Side" of the iPad. Creating assignments and in MBC and then having students submit them to that same assignment in MBC creates a work flow is quite simple. We have found that showing the students how to do it once at the start of the year in Computer class is sufficient for training them on the workflow. We are very pleased!!
Interested in your MY BIG CAMPUS implementation, I'm assuming thats part of teh LIGHTSPEED gateway authentication device? How do you r users authenticate, to gain access to the net? is it via a dedicated browser or the standard safari app?
We have also started using Studywiz at our College. It provides us a way for students to upload their work straight from their iPad into our Learning Management System. Yes. We also use WebDAV and Google Docs and so far this year, transferring documents hasn't been too much of an issue. Other options have included email, the Apple Camera Connection kit, Dropbox and Wireless sync with the students computer using iTunes.
It's awesome to see how educators are having their students create work on the iPad! For teachers who are looking for a super easy to use service to facilitate assignment or project file workflow between themselves and students, we've created a service called Showbie. With Showbie, teachers setup a class and assignments. They invite students to the class by giving the students a class code that links the student with all the assignments in the class once the student joins Showbie. This gives students each and assignment drop folder where they can upload work from their laptop via our website, or through our provided WebDAV server. If you're a teacher or student using an iPad app like Pages or Keynote, you can easily save work into your Showbie assignment folder by putting in the Showbie server URL (https://w.showbie.com) and then entering your Showbie login and password. Going forward, you won't need to put in these credentials unless you log out of the WebDAV connection.
If you have any questions or want to check us out, head over to http://www.showbie.com!
SHOWBIE from my experience is the most effective app to use for a workflow in class. I can access my account with my iPad, iPhone, iMac, PC and Andriod. It's versatility gives me the opportunity to keep in order all the lessons for the classes I teach. What once took 1 to 2 hours photocopying, giving handouts to student, collect their written responses, mark their work and give them feed back is done in a fraction of the time. Used in conjunction with the Explain Everything app and the students are able to hand in not just written responses but extend their work as engaging multimedia presentations to me. I have used this form of workflow since 2013 with enthusiasm for the learning and teaching process. As long as I have Internet access I can log into SHOWBIE.
Hi, I teach in a school with over 1000 iPads. I also provide support to teachers and other schools.
– AirStash A02 wireless USB from Meyers or online.
– Free Pocket DAV service to save from Pages to Google Drive.
– Dlink DIR 505 to save images, etc to external hard drive.
– WebDAV server at school.
What about letting every student make there own Google account (or use Google Apps as school) and let each of them share a folder from Google Drive with you as a teacher?
Wouldn't that solve the problem, at least partly?
I really feel for you. As a student I have to transfer plenty of files every day, and this "dark side" was always driving me crazy. Recently I have come across an application that changes the way you use your iPad.
I hope this facilitates your workflow somehow. I wish you good luck with your creative projects! Keep it up!
Great post, and some interesting replies.
I am new to teaching (in the UK) and the problem you describe is hitting me hard in the face. Individual bits of the technology for given tasks are amazing, but I just can't piece it together to give an efficient system for setting, receiving, reviewing and giving feedback on work, whilst also respecting the privacy of individual pupils. It's a huge issue, and surely one with a $$$-generating solution (the market is surely massive).
It's been a while since the original post. Has anything moved on? I suspect Apple have to move on this one? I'd love to hear a coherent solution from someone.
In a nutshell sharing is still not that intuitive however there is one app that gives users excellent access to cloud services and also sharing on the same network via a feature that they call Wi-Fi Drive. It works well.
Stuart, we are just looking at Showbie http://www.showbie.com as a system for presenting assignments, students can download to their iPad and "Open In" an app, do the work then open back in Showbie, uploading to their folder. Teacher can mark it up (say in a PDF markup app like PDF Expert), then they save it back in the students folder. Showbie are working on incorporating their own markup capabilities within the app to take out one of those intermediate steps.
We are still looking for a way to present a unit of work for students to be able to work through, a la Moodle, but not as clunky as that is on the iPad.
The "problem" with Showbie is that it is a subscription service, which makes it difficult for some teachers to take up and trial.
At our school, we use the File Browser app. It is a little like Goodreader, though simpler to use, with its file management system. It also connects to any form of remote server.
So our students can use the OPEN IN ANOTHER APP feature (of pretty much every app that creates or stores content) to save their own work into File Browser, from where they can submit to folders on local servers, that teachers have set up.
Edmodo works reasonably well, but if you don't have great Internet speed (as we don't), having a local server is the best option. A 150MB video file will transfer wirelessly in a minute or so, which is great.
I do agree with the idea of using Cloud services – the iCloud Sharing link, which gives live access via a web browser on a PC or Mac, looks great!
I just found this article, and wan to let you know that our FREE WebDAV client OverTheAir is the app which the Redlands College in your article is using.


Introduced at the fall 2016 Fort Lauderdale International Boat show, I was able to jump aboard Pursuit's new DC 235 Dual Console and get to know her up close and personal.
The DC235 is the smallest, entry level member of Pursuit's Dual Console fleet, which includes the DC 265, DC 295, DC 325 and the all new DC 365, which is the impressive flagship of this sorority. But the standard features and amenities of the compact DC 235 dual console make her anything but an entry-level player. She is loaded with all the right things in all the right places, but also includes an options list that allows owners to totally personalize their ride and their experience out on the water.
The Pursuit DC 235 has her act together and is an impressive family entertainment center for any of your waterborne activities. The full height transom bulkhead will keep following seas on the outside of the cockpit and allows room for a compact 15-gallon recirculating livewell tucked in the port corner and a transom gate set in the opposite side. A fold-down double wide aft bench adds welcome crew seating that stows into the transom bulkhead when not in use. The port side lounge seat features a unique engineering design that provides both a cushioned forward-facing bench with footrest and handrail, in addition to an aft-facing convertible seat with a neat flip-out extension that expands it into a convenient sun lounge setup, with a roomy storage area down below and access to a dedicated battery panel. The captain's helm seat is adjustable fore-and-aft to accommodate operators of all shapes and sizes and features a swivel mount, with integrated armrests and a flip-up seat/back bolster. The entertainment center set into a fiberglass module positioned just abaft of the helm seat offers a freshwater sink with pull-out sprayer, a poly cutting board, plus an insulated cooler capped off with a sturdy fiberglass lid.
A convenient flush hatch built into the cockpit sole set between the helm seats opens to reveal ample storage for skis, boards, fishing rods or whatever else you might have in mind for a fun family day out on the water. The port console offers a wide hinged opening to allow for easy transit down to the enclosed head area, with integrated storage, a molded headliner, a porcelain freshwater sink and manual head with 13-gallon holding tank, plus a 12-volt interior light. Moving forward through the opening center windshield and hinged doorway, the bow area includes twin bench seats with insulated storage below for your catch of the day or to keep additional gear dry and out from underfoot. An integrated anchor locker includes an anchor chute, 14-lb plow style anchor, 150-feet of rode and dedicated eight-inch cleat. A six-pack of eight-inch stainless steel pop-up cleats in the bow, stern and amidships makes dockside tie-ups a breeze. The helm features a dedicated spot to flush-mount a 12-inch multifunction display, with a compass, hydraulic steering and a handy breaker panel for your accessories.
Standard power on the Pursuit DC 235 is a Yamaha F250 V-6 four stroke outboard. If you want to enhance her performance even more, you can opt for the F300, which represents the max number of sea ponies you can hitch to her transom. Spinning a 17-inch pitch SWSII three-blade stainless steel prop, the DC 235 will hit a top speed of over 47-mph with three crew onboard, achieving her most fuel efficient cruising speed at 4000rpm, where this Florida gal will hit 31.1-mph on the GPS Nav, drinking 12.5-gallons per hour, for a net of 2.49-mpg. If you need to get to a hot bite pronto or are late to a beachside rendezvous, advancing the electronic throttle up to 4500 revs will turn 36.6-mph at 15.6-gph, for a bottom line of 2.35-mpg, so there is a minimal fuel consumption penalty for traveling in the fast lane. I have been on the center console version of Pursuit's latest 23-foot/21-degree aft deadrise hull and it's a smooth operator, producing excellent top end and cruising speeds, with welcome stability at rest and is relatively dry when underway. Her 105-gallon poly fuel tank will allow you to cruise to your favorite family fishing or entertainment spots over the course of a long weekend, plus enjoy water sports from sunup to sundown without needing to refuel. The swim platform extensions port and starboard aft are a nice touch and will allow easy egress and reentry when hitting the breach or coming back onboard. The fit and finish on this dual console is typical Pursuit quality and she will definitely turn some heads down at the marina. Notable standard features include LED Nav lighting, a high-tech hull with vinylester resin, a 3-ply resin-infused composite transom, fiberglass structural grid system, basic foam floatation, trim tabs with LED indicators and auto-retract feature and much more.


Sometimes under FTP classification Account shows different report suite or but different variables for same report suite for different login users.
FTP Classification Account Name : Products Categorization. Both report suites have same variable name but different variables used.
User 2 doesn't find Internal 'Internal Campaigns' variable.
Root Cause: Using different evars is the cause for this behavior.
Here you are using the same name, but they really refer to 2 different relationships (or variables eVar 1 and eVar 4).
What is most likely happening here is that one user when choosing the Internal search value it pulls the first report suite it sees, which then pulls that one variable and says are there any other report suites with this variable classified with this name. This results in different report suite retrieval for different users.
Changing the name of the evars would help. Then there will be two drop down items and will remove any confusion of which report suites to look at.


Hop on over to Amazon to snag this Abody LED UV Nail Lamp for only $26.59 shipped when you use promo code 9IBJ7CO7 at checkout.
This UV Nail Drying Lamp has five settings, an LCD digital display and 33 lights so you have even drying and curing of your gel polish. The removable base is easy to clean and it has a sensor that turns on the lamp when it detects when your hand is in it.


Response: Periodontal disease is a chronic oral inflammatory disease caused by bacterial infection, which affects 20% to 50% of the adult population. Lacunar stroke, a type of cerebral small vessel disease, is responsible for almost 25% of the ischaemic strokes. It may be hypothesized that chronic periodontitis leads to a low-grade state of systemic inflammation altering endothelial function and blood vessels health, which could be related to the onset of atherosclerosis. Moreover, lacunar stroke could be linked with an inflammation process that can be associated with endothelial dysfunction.
In the last decade, several observational studies have suggested an association between periodontal disease and ischaemic stroke. However, none of them have studied the relationship between chronic periodontitis and lacunar stroke independently of known vascular risk factors that both diseases may share (e.g., ageing, hypertension, diabetes mellitus or hypercholesterolemia).
Response: In our study, we investigated whether chronic periodontitis was associated with the presence of lacunar stroke in an age- and gender- matched sample.
A total of 122 subjects (62 patients diagnosed with lacunar infarct and 60 controls) were included in a case-control study. After full-mouth periodontal examination was performed in all subjects, we observed that chronic periodontitis was associated with lacunar infarct with an odds ratio of 4.20 (95% CI 1.81-10.20), independently of vascular risk factors.
Response: Patients diagnosed with periodontal disease have about a 4-fold higher risk of developing lacunar stroke compared with those without periodontitis. Clinicians should be aware of this link and give adequate counsellng to their patients on the prognosis implication of periodontitis. Due to chronic periodontitis is a treatable disease; periodontal therapy could decrease systemic inflammation as well as improve endothelial function and, therefore, may play a preventive role on the onset of lacunar infarct.
Response: First of all, we need prospective cohort studies with a long-term follow-up as well as pathophysiological studies in order to confirm and understand our findings. When a cause-effect relation is established, interventional studies should be carried out to assess the potential benefit of periodontal therapy in patients with periodontitis and lacunar stroke.
Response: In this case-control study we demonstrated that chronic periodontitis was associated with a significantly higher risk of lacunar infarct in a Spanish population. Further longitudinal and molecular studies are warranted to confirm our findings.
This entry was posted in Author Interviews, Dental Research, Stroke and tagged dental health, sroke by Marie Benz MD FAAD. Bookmark the permalink.


text:
MWFM Organization
Learning From Success Stories
Monarchs and Milkweeds in Farmscapes
Monarchs and Milkweeds on Highway Rights-of-Way
Monarchs and Milkweeds: What College Students Can Do
Contact your State Legislatures
Download the new Make Way for Monarchs posters
Nectar Plants
Milkweed Plants
The Kids Zone
Nursery Management Course
Michelle Obama creates first-ever 'pollinator garden' at the White House
By Make Way for Monarchs April 30, 2014
New addition to the sixth-annual White House Kitchen Garden meant to support bees, butterflies, and other essential pollinators.
The sixth edition of Michelle Obama's White House Kitchen Garden, planted on the South Lawn earlier this month, is now a bit more friendly to the insects we rely upon to pollinate our crops.
The First Lady announced the addition of the first-ever "White House Pollinator Garden," a plot designed to not only assist the more than 70,000 bees that make up the White House honeybee hive, but also butterflies, moths, and other insects that contribute to pollination.
"We're going to plant all kinds of flowers that attract bees and butterflies – which is not really going to make the Obama girls happy, because they don't like bees – but bees are good," Mrs. Obama explained to local students and FoodCorps leaders.
Pollinator gardens are generally composed of a variety native plants that bloom from early spring into late fall. Plants such as aster, sunflower, lavender, yarrow, borage, and fennel are all great examples of attractive species. Keeping everything organic and free of pesticides is also key.
"Another suggestion is when selecting your plants, to remember that native bees tend to be attracted to flowers that are blue, purple, and yellow," shares Claire Cassel of the Fish and Wildlife Service. "Hummingbirds on the other hand, are attracted to red flowers. Butterflies are attracted to a wide range of colors. And plants that flower at night such as gourds and evening glories will attract a variety of moths with their white blooms and in some cases sweet fragrance."
Check out the First Lady working with kids and volunteers on the latest Kitchen Garden below.
ref: Mother Nature Network
Vermont New Farmer Project – Upcoming Webinar with John Hayden
Enhancing Native Pollinator Populations on Farms. We need these farming partners to pollinate our fruit and vegetable crops, yet our native pollinators and honey bees are struggling from multiple threats of pesticide exposure, habitat loss, parasites and diseases.
John Hayden from The Farm Between in Jeffersonville, VT will present on who the native pollinators are, why they are in trouble…
Billions More Milkweeds Needed to Restore Monarchs
Monarchs rely on milkweeds for food and for breeding habitat, but over 860 million stems were lost in the northern United States over the last decade. Scientists with the USGS and partners examined the density of Eastern migratory monarch butterflies overwintering in Mexico from 1979-2002 and the amount of milkweed plants available to them in North America.
The study found that 3.62 billion milkweed stems are needed to reestablish this monarch population, but only 1.34 billion stems remain in the U.S.
Birds, Bees And The Power Of Sex Appeal: The Ribald Lives Of Flowers
Flowers, bugs and bees: Stephen Buchmann wanted to study them all when he was a kid. "I never grew out of my bug-and-dinosaur phase," he tells NPR's Arun Rath. "You know, since about the third grade, I decided I wanted to chase insects, especially bees."
These days, he's living that dream. As a pollination ecologist, he's now taking a particular interest in how flowers attract insects. In his new book, The Reason for Flowers, he looks at more than just the biology of flowers — he dives into the ways they've laid down roots in human history and culture, too.
Are gardeners doing monarchs more harm than good by planting Mexican milkweed?
Monarchs have been in the news a lot lately, most of it grim. Numbers have dropped dramatically over recent years from various causes, including climate change, illegal logging at the insects' overwintering sites in Mexico and new practices in the agricultural industry.
A major factor is the widespread use of GMO crops that are Round-Up resistant, allowing U.S. farmers in the monarch's summer breeding grounds in the Corn Belt to spray the herbicide on their fields to kill weeds.
The vanishing monarch butterfly
Nearly every autumn, I head to the hills to band and release hawks, eagles and other powerful raptors as they ride the mountains' updraft on their southern migration. While there, I always used to marvel at another autumnal migrant, tiny but no less magnificent — monarch butterflies, flapping earnestly on their delicate wings, dappling the ridge top orange and black.
Although they weigh less than a tenth-of-an-ounce, the monarchs' 2,500-mile annual transcontinental journey to Mexico is longer than that of most raptors. They fly north from Mexico across the Midwest and up the eastern seaboard, to Canada — and back again, all in one summer. The yearly trek requires several generations.
Monarch Decline
The migratory monarch butterfly population has been decimated in recent years, with a total population decline of 90 percent over the past two decades.
But the dying butterflies are a bellweather for even bigger environmental damage.
Monarchs and Milkweeds in Farmscapes: Making Safe Havens through Planting Conservation Strips in Highly Diverse, Low Input Fields, Orchards and Pastures
It is likely that at least 170,000,000 acres of actively-sown annual field crops in American farmscapes are now depleted of their formerly-abundant milkweeds and monarch butterflies.
Monarch butterflies cross U.S., Mexico to unite culture and conservation
In Chicago, hundreds of Mexican-American families are growing monarch butterflies, watching a caterpillar ball up into a green chrysalis,…
Make Way for Monarchs
Did you know that one in every three bites of food you take required a pollinator visit? Pollination is essential for many of our favorite foods—from almonds to vanilla, and so many fruits and vegetables in between.
The decline of pollinators around the world is threatening not only our food supply but also the function of plant communities and ecosystems.
Imperiled Monarch Butterflies Get $3.2 Million From U.S. Government
Monarch butterflies have experienced a breathtaking decline in the past 20 years, going from a billion strong in 1996 to roughly 30 million today because of habitat destruction. On Monday, the U.S. government announced the first federal pot of money for rescuing monarchs, with the Fish and Wildlife Service earmarking $3.2 million for the effort.
About $2 million will go toward conservation programs…
Dear Obama, Trudeau and Peña Nieto: Act Now to Save the Monarch Butterfly
More than 200 scientists, writers and artists have signed a letter addressed to Mexican President Enrique Peña Nieto, U.S. President Barack Obama and Canadian Prime Minister Justin Trudeau, in advance of the North American Leaders' Summit in Ottawa later this month.
The signers urge that swift and energetic actions be taken to save the monarch butterfly from the threats that endanger its survival. All three countries must work together to mitigate the loss of the butterflies' breeding habitat and to terminate all logging and mining in the Monarch Butterfly Biosphere Reserve in Michoacan, Mexico.
Why You Should Worry About The Butterflies
We love butterflies, and monarch butterflies are called "monarch" for a reason. They are grand. All that fluttering orange and black display on a winged scale built to impress. To charm. But monarch butterflies are in trouble.
This year saw the smallest migration ever recorded to their winter retreat in the mountains of Mexico.
Number of Monarchs Overwintering in California Remains Low
A survey of monarch butterflies overwintering in California shows that the population has not rebounded. Although the total number of monarchs counted this year was greater than last, the difference is due to a large increase in volunteer effort. Counts at major sites were down when compared to recent years.
Volunteers with the Xerces Society's Western Monarch Thanksgiving Count visited 253 sites and tallied a total of 298,464 monarchs—a fraction of the 1.2 million monarchs recorded in the late 1990s.
Keep Calm and Plant Milkweed
Recently there have been a number of articles in the press about how people are planting the wrong kind of milkweed and that it's actually harming monarch butterflies. Inflammatory headlines have warned about how well intentioned people may actually be "destroying" monarchs and how "the plan to save monarchs" by planting milkweed has "backfired."
Well, I'm here to tell you that there is no need to freak out. And Please, KEEP PLANTING MILKWEED! Here's why.
Iconic monarch butterflies under threat from rising herbicide use
Monarch butterflies are known for their striking flame-orange and black appearance, and especially for their mass migration in their millions to spend winters in the mountain forests of Mexico. But despite growing problems with deforestation in Mexico, their struggle begins at home in the United States and Canada.
The butterflies that fly to Mexico are the great-great-great grandchildren of the monarchs that were in Mexico the previous winter. In 2013 the overwintering population in Mexico covered 0.67 hectares of fir forest (about 44 million butterflies) the lowest since counts began in 1994.
MWFM is aiming to safeguard the biodiversity in the "milkweed community" in the face of excessive or non-targeted use of herbicides, climate change and other threats in both farmscapes and roadside vegetation along the migratory corridors of monarchs.
'One tough little butterfly': Monarch Watch uses citizen science to track butterflies from Canada to Mexico
Long Island Woman Raises Thousands Of Majestic Monarch Butterflies, Prepares Them For An Epic Flight
New study on migration success reinforces need for monarch butterfly milkweed habitat
Search The Monarchs
MWFM © Copyrights 2014-2020


Major European forex broker FxPro has announced the launch of its "revolutionary" spread betting platform FxPro Edge.
It is available for clients of FxPro UK that are residents of the United Kingdom, starting from August 11. On FxPro Edge traders can spread bet on forex, spot indices, shares, spot metals and spot energies, with no commission and benefit from FxPro's order execution.
"We are committed to consistently providing our clients with new ways to invest in the financial markets. Spread Betting has risen in popularity in recent years, and with FxPro Edge, our clients can now experience the benefits of this new investment method, reinforced by our professional trading conditions and industry-leading No Dealing Desk Execution", said FxPro CEO, Charalambos Psimolophitis.
The FxPro Edge platform is launched to commemorate the beginning of the 2017/18 Premier League season and the first game of FxPro and Watford FC's 3-year sponsorship deal.
FxPro is regulated jointly by Cyprus' Securities and Exchange Commission (CySEC) and UK's FCA. The broker operates as a Hybrid Agency Model broker, offering Negative Balance Protection and enabling clients to access top-tier liquidity. It offers complete services for all retail forex market segments, as well as trading in futures, indices, metals, shares, and CFDs on a selection of trading platforms, including MetaTrader 4 and 5 and cTrader.


text:
Psalm 72 :: King James Version (KJV)
The Reign of the Righteous King. ©
Psa 72:1
Psa 72:1 - [[A Psalm for Solomon.]] Give the king thy judgments, O God, and thy righteousness unto the king's son.
Psa 72:2 - He shall judge thy people with righteousness, and thy poor with judgment.
Psa 72:3 - The mountains shall bring peace to the people, and the little hills, by righteousness.
Psa 72:4 - He shall judge the poor of the people, he shall save the children of the needy, and shall break in pieces the oppressor.
Psa 72:5 - They shall fear thee as long as the sun and moon endure, throughout all generations.
Psa 72:6 - He shall come down like rain upon the mown grass: as showers that water the earth.
Psa 72:7 - In his days shall the righteous flourish; and abundance of peace so long as the moon endureth.
Psa 72:8 - He shall have dominion also from sea to sea, and from the river unto the ends of the earth.
Psa 72:9 - They that dwell in the wilderness shall bow before him; and his enemies shall lick the dust.
Psa 72:10
Psa 72:10 - The kings of Tarshish and of the isles shall bring presents: the kings of Sheba and Seba shall offer gifts.
Psa 72:11 - Yea, all kings shall fall down before him: all nations shall serve him.
Psa 72:12 - For he shall deliver the needy when he crieth; the poor also, and him that hath no helper.
Psa 72:13 - He shall spare the poor and needy, and shall save the souls of the needy.
Psa 72:14 - He shall redeem their soul from deceit and violence: and precious shall their blood be in his sight.
Psa 72:15 - And he shall live, and to him shall be given of the gold of Sheba: prayer also shall be made for him continually; and daily shall he be praised.
Psa 72:16 - There shall be an handful of corn in the earth upon the top of the mountains; the fruit thereof shall shake like Lebanon: and they of the city shall flourish like grass of the earth.
Psa 72:17 - His name shall endure for ever: his name shall be continued as long as the sun: and men shall be blessed in him: all nations shall call him blessed.
Psa 72:18 - Blessed be the LORD God, the God of Israel, who only doeth wondrous things.
Psa 72:19 - And blessed be his glorious name for ever: and let the whole earth be filled with his glory; Amen, and Amen.
Psa 72:20 - The prayers of David the son of Jesse are ended.
The Authorized Version or King James Version (KJV), 1611, 1769.
Outside of the United Kingdom, the KJV is in the public domain. Within the United Kingdom, the rights to the KJV are vested in the Crown.
Pericope taken from the NASB95 and has been graciously provided by The Lockman Foundation, La Habra, Calif. All rights reserved.
Copyright © 1960, 1962, 1963, 1968, 1971, 1972, 1973, 1975, 1977, 1995
by The Lockman Foundation, La Habra, Calif.
WLC Westminster Leningrad Codex
LXX Septuagint