WAVE3-NFκB Interplay Is Essential for the Survival and Invasion of Cancer Cells

The WAVE3 cytoskeletal protein promotes cancer invasion and metastasis. We have shown that the WAVE3-mediated activation of cancer cell invasion is due, in part, to its regulation of expression and activity of key metalloproteinases (MMPs), including MMP9, which is centrally involved in invadopodia-mediated degradation of the extracellular matrix (ECM). MMP9 is also a major NFκB target gene, suggesting a potential linkage of WAVE3 to this pathway, which we sought to investigate. Mechanistically, we found that loss of WAVE3 in cancer cells leads to inhibition of NFκB signaling as a result of a decrease in the nuclear translocation of NFκB and therefore loss of activation of NFκB target genes. Conversely, overexpression of WAVE3 was sufficient to enhance NFκB activity. Both pharmacologic and genetic manipulations of NFκB effector molecules show that the biological consequence of loss of WAVE3 function in the NFκB pathway result the inhibition of invadopodia formation and ECM degradation by cancer cells, and these changes are a consequence of decreased MMP9 expression and activity. Loss of WAVE3 also sensitized cancer cells to apoptosis and cell death driven by TNFα, through the inhibition of the AKT pro-survival pathway. Our results identify a novel function of WAVE3 in NFκB signaling, where its activity is essential for the regulation of invadopodia and ECM degradation. Therefore, targeted therapeutic inhibition of WAVE3 will sensitize cancer cells to apoptosis and cell death, and suppress cancer invasion and metastasis.     

Effect of post-mating GnRH analogue (buserelin) treatment on PGF2alpha release in ewes and ewe lambs

The objectives of this study were to determine the effects of buserelin or saline treatment on ovarian function (Experiment 1), plasma PGFM concentrations and oxytocin stimulated prostaglandin F(2alpha) (PGF(2alpha)) release (Experiment 2) in ewe lambs and ewes. Welsh Halfbred ewes (n=26) and ewe lambs (n=24) were mated to vasectomised rams at synchronised oestrus and on Day 12 post-mating each animal was injected intramuscularly either normal saline or 4 microg buserelin. In Experiment 1, plasma progesterone and oestradiol concentrations were determined in samples collected by jugular venepuncture 1h before and at 0, 2, 4, 6, 8, 24, 48 and 72 h after treatment (n=7 per treatment group). Progesterone concentrations increased (P<0.05) from 2 to 8h after buserelin treatment and returned to basal levels after 72 h, whereas oestradiol concentrations were maximal at 2h post-treatment and returned to basal levels after 24h (P<0.05). Oestradiol concentrations were lower (P<0.05) in buserelin-treated animals than controls at 72 h post-treatment. Basal and post-treatment progesterone concentrations were greater (P<0.05) in ewes than in ewe lambs but oestradiol levels were similar for both age groups. Ovulation rate, determined by laparoscopy on Day 14, was similar for both age groups (ewes 1.1; ewe lambs 1.0). Buserelin treatment induced accessory corpora lutea in ewes (4/7; 57%) but not in ewe lambs (0/7; 0%). In the Experiment 2, plasma PGFM concentrations were determined in samples collected at 20-min intervals for 6h on Day 14 and at 20-min intervals for 1h before and at 10-min intervals for 1h and then at 20-min intervals for a further 3h period after an intravenous injection of oxytocin (1IU/kg body weight) on Day 15 post-oestrus. In this experiment there were five ewe lambs and six ewes per treatment group. There was no effect of buserelin treatment or age on basal PGFM concentrations on either Day 14 or 15. Although peak PGFM concentrations tended to be lower in buserelin-treated animals, the difference was not significant (P>0.05). However, peak duration following oxytocin challenge on Day 15 post-mating was shorter (P<0.05) in control ewes compared with control ewe lambs. In conclusion, buserelin treatment given on Day 12 post-oestrus enhances luteal function more in ewes than ewe lambs and after a transitory increase, reduces oestradiol concentrations in both ewes and ewe lambs. However, buserelin treatment does not significantly attenuate the luteolytic signal.     

Antibacterial cobalt (II), copper (II), nickel (II) and zinc (II) complexes of mercaptothiadiazole--derived furanyl, thienyl, pyrrolyl, salicylyl and pyridinyl Schiff bases

A series of Co (II), Cu (II), Ni (II) and Zn (II) complexes of mercaptothiadiazole-derived furanyl, thienyl, pyrrorlyl, salicylyl and pyridinyl Schiff bases were synthesized, characterized and screened for their in vitro antibacterial activity against four Gram-negative, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Shigella fexneri, and two Gram-positive; Bacillus subtilis and Staphylococcus aureous bacterial strains. The results of these studies show the metal complexes to be more antibacterial as compared to the prepared un-complexed Schiff bases.     

The responses of Apis mellifera jemenitica to different artificial queen rearing techniques

In the current study, we investigated if any variations exist in acceptance rate of grafted larvae and quality of queens reared in different queen cell cup sizes, between wet and dry grafting and between queen right and queen less conditions of A. m. jemenitica colonies. The acceptance rate of grafted larvae in different queen cell cup sizes (7.0 mm, 7.5 mm, 8.0 mm, 8.5 mm) were varying from 69 to 71% and the variations were not significant among the different queen cups sizes but averagely lower than the acceptances recorded for other races. Out of the 172 dry grafted larvae, only 56.4% of them were accepted while in wet grafting out of 174 grafted larvae 77.01% were accepted. Regarding the rate of sealing, 48.84% and 71.84% of them sealed for dry and wet grafts, respectively. The observed variation in the rate of acceptance and sealing were significant (N = 346, df = 1, P < 0.0001) between the two techniques. However, there was no significant difference in fresh weight of emerged queens between the two grafting methods. Out of the 324 grafted larvae given to queen right and queen less starter colonies each; 106 (32.72%) and 252 (73.68%) were accepted in queen right and queen less starter colonies, respectively and the variation was highly significant at P < 0.0001. The total number of sealed pupae were 82 (25.31%) and 216 (63.16%) for queen right and queen less colonies, respectively and the variations was significant at P < 0.0001. From the study it can be concluded that A. m. jemenitica colonies can rear significantly more queens under wet grafting and in queen less colonies conditions than dry grafting and queen right conditions     

Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis

Objective To determine the accuracy of using systolic and diastolic blood pressure, mean arterial pressure, and increase of blood pressure to predict pre-eclampsia.Design Systematic review with meta-analysis of data on test accuracy.Data sources Medline, Embase, Cochrane Library, Medion, checking reference lists of included articles and reviews, contact with authors.Review methods Without language restrictions, two reviewers independently selected the articles in which the accuracy of blood pressure measurement during pregnancy was evaluated to predict pre-eclampsia. Data were extracted on study characteristics, quality, and results to construct 2×2 tables. Summary receiver operating characteristic curves and likelihood ratios were generated for the various levels and their thresholds.Results 34 studies, testing 60 599 women (3341 cases of pre-eclampsia), were included. In women at low risk for pre-eclampsia, the areas under the summary receiver operating characteristic curves for blood pressure measurement in the second trimester were 0.68 (95% confidence interval 0.64 to 0.72) for systolic blood pressure, 0.66 (0.59 to 0.72) for diastolic blood pressure, and 0.76 (0.70 to 0.82) for mean arterial pressure. Findings for the first trimester showed a similar pattern. Second trimester mean arterial pressure of 90 mm Hg or more showed a positive likelihood ratio of 3.5 (95% confidence interval 2.0 to 5.0) and a negative likelihood ratio of 0.46 (0.16 to 0.75). In women deemed to be at high risk, a diastolic blood pressure of 75 mm Hg or more at 13 to 20 weeks’ gestation best predicted pre-eclampsia: positive likelihood ratio 2.8 (1.8 to 3.6), negative likelihood ratio 0.39 (0.18 to 0.71). Additional subgroup analyses did not show improved predictive accuracy.Conclusion When blood pressure is measured in the first or second trimester of pregnancy, the mean arterial pressure is a better predictor for pre-eclampsia than systolic blood pressure, diastolic blood pressure, or an increase of blood pressure.     

Concentration dependent growth/non-growth linked kinetics of endosulfan biodegradation by <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>

The rates of biodegradation of endosulfan by P. aeruginosa were determined with different initial endosulfan concentrations (10, 50, 100, 150, 200 and 250 mg l⁻¹) and different growth linked kinetic models were fitted at these concentrations. At 10 mg endosulfan l⁻¹, Monod no growth model was well fitted. Monod with growth model described the biodegradation pattern at an initial concentration of 50, 100 and 150 mg endosulfan l⁻¹. Significant increases of P. aeruginosa MN2B14 density in broth culture during incubation further support this result. Conversely, zero order kinetic model was well fitted into the biodegradation data if initial endosulfan concentration was ≥200 mg endosulfan l⁻¹. The kinetics of endosulfan biodegradation by P. aeruginosa MN2B14 in liquid broth was highly dependent upon its initial concentration. The results of this study could be employed for predicting the persistence of endosulfan in water environment containing P. aeruginosa as an endosulfan degrading bacterium.