Araguspongine C Induces Autophagic Death in Breast Cancer Cells through Suppression of c-Met and HER2 Receptor Tyrosine Kinase Signaling

Receptor tyrosine kinases are key regulators of cellular growth and proliferation. Dysregulations of receptor tyrosine kinases in cancer cells may promote tumorigenesis by multiple mechanisms including enhanced cell survival and inhibition of cell death. Araguspongines represent a group of macrocyclic oxaquinolizidine alkaloids isolated from the marine sponge Xestospongia species. This study evaluated the anticancer activity of the known oxaquinolizidine alkaloids araguspongines A, C, K and L, and xestospongin B against breast cancer cells. Araguspongine C inhibited the proliferation of multiple breast cancer cell lines in vitro in a dose-dependent manner. Interestingly, araguspongine C-induced autophagic cell death in HER2-overexpressing BT-474 breast cancer cells was characterized by vacuole formation and upregulation of autophagy markers including LC3A/B, Atg3, Atg7, and Atg16L. Araguspongine C-induced autophagy was associated with suppression of c-Met and HER2 receptor tyrosine kinase activation. Further in-silico docking studies and cell-free Z-LYTE assays indicated the potential of direct interaction between araguspongine C and the receptor tyrosine kinases c-Met and HER2 at their kinase domains. Remarkably, araguspongine C treatment resulted in the suppression of PI3K/Akt/mTOR signaling cascade in breast cancer cells undergoing autophagy. Induction of autophagic death in BT-474 cells was also associated with decreased levels of inositol 1,4,5-trisphosphate receptor upon treatment with effective concentration of araguspongine C. In conclusion, results of this study are the first to reveal the potential of araguspongine C as an inhibitor to receptor tyrosine kinases resulting in the induction of autophagic cell death in breast cancer cells.     

Performance of three endophytic actinomycetes in relation to plant growth promotion and biological control of <Emphasis Type="Italic">Pythium aphanidermatum</Emphasis>, a pathogen of cucumber under commercial field production conditions in the United Arab Emirates

In the current study, the performance of three endophytic actinomycetes identified as Actinoplanes campanulatus, Micromonospora chalcea and Streptomyces spiralis previously shown to reduce seedling damping-off, and root and crown rots of mature cucumber (Cucumis sativus) caused by Pythium aphanidermatum in pots under greenhouse conditions were further evaluated to determine their potential as biological control agents and as plant growth promoters in the field under the conditions of commercial production of cucumbers in the United Arab Emirates (UAE). When applied individually or in combination to cucumber seedlings, the three isolates significantly promoted plant growth and yield and reduced seedling damping-off and root and crown rots of mature cucumber plants. Individually the performance level of S. spiralis was relatively the best followed by A. campanulatus and then by M. chalcea. The three isolates (which were not inhibitory to each other) performed better, both as biological control agents as well as plant growth promoters, when applied together than when they were inoculated individually. The ability of these three isolates to colonize the internal tissues of roots, stems and leaves under field conditions, and to persist up to 8 weeks after seedling inoculation, showed that they can easily adapt to an endophytic habit systemically within healthy cucumber plants. As the three endophytic actinomycete isolates also colonized the rhizosphere and showed outstanding rhizosphere competency it is clear that they are facultative and not obligate endophytes. The success with the three inoculants indicated that they could well be used in place of the fungicide metalaxyl which is currently recommended for the management of Pythium diseases in the UAE. This is the first successful field use of endophytic actinomycetes as promising plant growth promoters and biological control agents against Pythium diseases of cucumber.     

<Emphasis Type="Italic">Vicia faba</Emphasis> plants respond to oviposition by invasive <Emphasis Type="Italic">Halyomorpha halys</Emphasis> activating direct defences against offspring

The invasive stink bug Halyomorpha halys is established in many European and American agro-ecosystems, where it causes severe crop losses. Potential control measures might include enhancement of plant defences. When attacked by herbivorous insects that oviposit on it, the plant may respond by priming direct defences, which might affect the development of future brood. Halyomorpha halys attacks numerous plant species in the invaded areas. Here, we investigated whether Vicia faba plants challenged by H. halys females can impair the development of its offspring through the activation of induced direct defences. We measured the weight and dimension of nymphs that developed on oviposition-experienced plants after 7 and 17 days from hatching. Nymphs that developed on oviposition-experienced plants weighed less compared to those that developed either on control plants or on plants solely subjected to H. halys feeding, and third instars showed shorter dimensions (tibia length). In addition, when oviposition-experienced plants were attacked by nymphs, higher and more rapid expression of two jasmonic acid-dependent genes (cysteine proteinase inhibitor gene and NAI1) was detected, possibly due to a mechanism of priming. Increased expression of the salicylic acid-responsive PR1 gene was also detected in egg-experienced plants, although the response was delayed compared to JA-dependent genes. Our results suggest that V. faba plants recognize H. halys oviposition as a warning signal and pre-activate defences against future nymphal herbivory.     

Reduction of virgin olive oil bitterness by fruit cold storage

Green mature olives (Olea europaea L. cv. 'Manzanilla', 'Picual', and 'Verdial') were stored at 5 degrees C, and the oil extracted from them showed a middle intensity level of sensory-evaluated bitterness. The storage times necessary for this reduction were different for the three varieties tested, requiring 4, 6, and 8 weeks, respectively, for 'Manzanilla', 'Picual', and 'Verdial' olives. The level of commercial quality of the extracted oil did not deteriorate as a consequence of previous fruit storage. Olives matured during refrigeration at 5 degrees C, as the increase of maturation index and the decrease of color index and fruit firmness indicated. Similarly, as the fruit storage period progressed, the total phenolic compound content of the extracted oils decreased. Although the use of green mature olives may require a more prolonged storage time, it allows for a better postharvest handling of the fruits, which are more resistant to physical damage or fungal infections than the riper ones.     

Structure of the 4-O-[1-Carboxyethyl]-d-Mannose-Containing O-Specific Polysaccharide of a Halophilic Bacterium Salinivibrio sp. EG9S8QL

The moderately halophilic strain Salinivibrio sp. EG9S8QL was isolated among 11 halophilic strains from saline mud (Emisal Salt Company, Lake Qarun, Fayoum, Egypt). The lipopolysaccharide was extracted from dried cells of Salinivibrio sp. EG9S8QL by the phenol–water procedure. The OPS was obtained by mild acid hydrolysis of the lipopolysaccharide and was studied by sugar analysis along with ¹H and ¹³C NMR spectroscopy, including ¹H,¹H COSY, TOCSY, ROESY, ¹H,¹³C HSQC, and HMBC experiments. The OPS was found to be composed of linear tetrasaccharide repeating units of the following structure: →2)-β-Manp4Lac-(1→3)-α-ManpNAc-(1→3)-β-Rhap-(1→4)-α-GlcpNAc-(1→, where Manp4Lac is 4-O-[1-carboxyethyl]mannose.     

Characterizing and predicting plant phenology in species‐rich grasslands

The use of plant phenology for determining the timing of management practices is poorly understood in species‐rich grasslands. The objectives were to assess the effect of management practices on the dates at which phenological stages occur and to compare different methods of calculating the growing degree‐days in order to predict them. Dates at which phenological stages of plant species occurred were recorded and plant strategy for resource capture and use was assessed through measurements of the dry matter content of leaves in two experiments in regions with contrasting climatic conditions. In Experiment 1, conducted near Toulouse, France, a set of 31 species was sown in pure stands at two levels of N availability. In Experiment 2, a network of 18 permanent grasslands, located in the French Pyrenees, was studied. In both experiments, the dry matter content of leaves, and flowering and ripening times, were measured. In Experiment 1, the dates on which a given phenological stage occurred were correlated with one another, and the grass species showed a significant ranking of dry weight of leaves for these dates. In Experiment 2, the difference between average flowering times of plant communities was shown to be around 40 d and resulted more from the species composition of the plant community than from their sensitivity to management practices. Plant communities were significantly ranked by dry weight of leaves for their flowering time. The minimum and maximum base temperatures which minimized the growing degree‐days between the two locations were 0 and 25°C, respectively, and the most appropriate date from which to start to accumulate temperatures was found to be 1 February.     

Genetic parameters of survival in four generations of Indian white shrimp (Fenneropeneaus indicus)

This study evaluated the genetic variance for survival at harvest of Indian white shrimp (Fenneropenaeus indicus) using a pedigreed synthetic population generated upon collecting broodstock from different fishery grounds in Egypt. The estimated heritabilities (h² ± SE) of survival from generations G₀ to G₃ ranged from 0.144 ± 0.026 to 0.008 ± 0.030 using a model that included the common environmental effect (c²). Low heritability (0.014 ± 0.015) was estimated across generations with the inclusion of common environmental effect (c²). However, the h² of survival from G₀ to G₁ ranged from 0.569 ± 0.071 to 0.410 ± 0.011 when c² was not included. The genetic correlation for survival between different ponds from G₀ to G₃ was moderate to high (0.79 ± 0.042 to 0.83 ± 0.012) but significantly different (P < 0.05). There were low correlation coefficients (?0.237 ± 0.089 to 0.316 ± 0.073) between body weight estimated breeding value (EBV) and survival EBV of families in four generations.     

Influence of high temperature on cadmium-induced skeletal deformities in juvenile mosquitofish (<Emphasis Type="Italic">Gambusia affinis</Emphasis>)

The aim of this study was to assess the effect of high temperature on cadmium (Cd)-induced skeletal deformities in juvenile Mosquitofish, Gambusia affinis. For this purpose, 188 juveniles (1 day old) were equally divided into the control group, which was maintained in Cd-free water at 24°C, and three treated groups exposed either to Cd (0.4 mg/l as Cd Cl₂) at 24°C, to high temperature (32°C), or to Cd at 32°C for 30 days. The results showed that Cd exposure at 24°C significantly increased the Cd accumulation (P < 0.0001) in the whole tissues of juveniles as well as the incidence of skeletal deformities (P < 0.01) compared with control animals. Exposure to high temperature also led to a significant increase in the incidence of skeletal deformities (P < 0.01) with respect to the control group. Interestingly, our results showed that the combined exposure to Cd and high temperature led to a more significant increase in Cd accumulation and in the frequency of spinal deformities than exposure to Cd or high temperature alone. These results confirm that temperature increases Cd toxicity and needs to be taken into account for the accurate prediction and assessment of Cd-induced spinal deformities in fish.     

Utilization of some organic wastes as growing media for lettuce (Lactuca sativa L.) plants

Abstract

The environmental impact of crop wastes and the high cost of peat moss (PM) force scientists to find alternative growing media. In a pot experiment, peanut shell (PS) and corn wastes (CWs) were evaluated as growing media in comparison with PM in three different mixing ratios with washed sand. The mixing ratio were M₁?=?1:1 raw material to sand, M₂?=?1:2 raw material to sand, and M₃?=?1:3 raw material to sand. The tested plant was lettuce (Lactuca sativa L.). The obtained results showed that PS medium contained available nitrogen (N) and phosphorus (P) higher by 121% and 38% above the PM medium. Availability of potassium (K) in CW medium was higher by 167% than PM. The EC, pH, OC, and C/N ratio of PM were higher by 227%, 4%, 128%, and 99% above the CW and by 1,473%, 9%, 74%, and193% above the PS, respectively. The highest significant values of growth parameters were recorded in PM medium. The highest total cost and lowest net profit were recorded with the use of PMM₁, whereas the lowest cost and the highest net profit were obtained with PSM₂. Physiochemical characteristics of peanut shell suggested that it can be economical alternative growing media for PM.