Oncolytic specificity of Newcastle disease virus is mediated by selectivity for apoptosis-resistant cells

Newcastle disease virus (NDV) is a negative-sense RNA virus that has been shown to possess oncolytic activity. NDV's selective replication in tumor cells has been previously suggested to be due to the lack of a proper antiviral response in these cells. Here we demonstrate that NDV possesses oncolytic activity in tumor cells capable of a robust type I interferon (IFN) response, suggesting that another mechanism underlies NDV's tumor specificity. We show that the oncolytic selectivity of NDV for tumor cells is dependent upon tumor cell resistance to apoptosis. Utilizing the human non-small-cell lung cancer cell line A549 overexpressing the antiapoptotic protein Bcl-xL, we show significant enhancement of oncolytic activity and NDV replication. Interestingly, while the Bcl-xL-overexpressing cells were resistant to apoptotic stimuli induced by chemotherapeutic agents and early viral replication, during the subsequent viral cycles, we observed a paradoxical increase in apoptosis in response to NDV. The increased oncolytic activity seen was secondary to enhanced viral replication and syncytium formation. The induction of a type I IFN response was enhanced in Bcl-xL cells. Overall, these findings propose a new mechanism for cancer cell specificity for NDV, making it an attractive anticancer agent for chemoresistant tumors with enhanced antiapoptotic activity.     

Convergent evolution of morphological and ecological traits in the open-habitat chat complex (Aves, Muscicapidae: Saxicolinae)

Snails in the closely related trochid genera Phorcus Risso, 1826 and Osilinus Philippi, 1847 are ecologically important algal grazers in the intertidal zone of the northeastern Atlantic Ocean and Mediterranean Sea. Here we present the first complete molecular phylogeny for these genera, based on the nuclear 28S rRNA gene and the mitochondrial 16S rRNA and COI genes, and show that the current classification is erroneous. We recognize nine species in a single genus, Phorcus: estimated by BEAST analysis, this arose 30 (±10) Ma; it consists of two subgenera, Phorcus and Osilinus, which we estimate diverged 14 (±4.5) Ma. Osilinus kotschyi, from the Arabian and Red Seas, is not closely related and is tentatively referred to Priotrochus Fischer, 1879. Our phylogeny allows us to address biogeographical questions concerning the origins of the Mediterranean and Macaronesian species of this group. The former appear to have evolved from Atlantic ancestors that invaded the Mediterranean on several occasions after the Zanclean Flood, which ended the Messinian Salinity Crisis 5.3 Ma; whereas the latter arose from several colonizations of mainland Atlantic ancestors within the last 3 (±1.5) Ma.     

Exploring the interaction of myricetin with human alpha-2-macroglobulin: biophysical and in-silico analysis

Myricetin (MYR) is a bioactive secondary metabolite found in plants that is recognized for its nutraceutical value and is an essential constituent of various foods and beverages. It is reported to exhibit a plethora of activities, including antioxidant, antimicrobial, antidiabetic, anticancer, and anti-inflammatory. Alpha-2-macroglobulin (α2M) is a major plasma anti-proteinase that can inhibit proteinases of both human and non-human origin, regardless of their specificity and catalytic mechanism. Here, we explored the interaction of MYR-α2M using various biochemical and biophysical techniques. It was found that the interaction of MYR brings subtle change in its anti-proteolytic potential and thereby alters its structure and function, as can be seen from absorbance and fluorescence spectroscopy. UV spectroscopy of α2M in presence of MYR indicated the occurrence of hyperchromism, suggesting complex formation. Fluorescence spectroscopy reveals that MYR reduces the fluorescence intensity of native α2M with a shift in the wavelength maxima. At 318.15 K, MYR binds to α2M with a binding constant of 2.4 × 10³ M⁻¹, which indicates significant binding. The ΔG value was found to be − 7.56 kcal mol⁻¹ at 298.15 K, suggesting the interaction to be spontaneous and thermodynamically favorable. The secondary structure of α2M does not involve any major change as was confirmed by CD analysis. The molecular docking indicates that Asp-146, Ser-172, Glu-174, and Tyr-180 were the key residues involved in α2M-MYR complex formation. This study contributes to our understanding of the function and mechanism of protein and flavonoid binding by providing a molecular basis of the interaction between MYR and α2M.     

Sublethal effects of essential oil of Cinnamomum zeylanicum Blume on life expectancy (ex) and age-specific fertility (mx) of two-spotted spider mite,Tetranychus urticae Koch (Acari: Tetranychidae)

Two-spotted spider mite, Tetranychus urticae Koch, is one of the most important pests of agricultural products that have a global distribution. Now, the control is dependent on the use of chemical pesticides. The effects of the sublethal concentrations (LC₁₀ and LC₂₅) of the essential oil of Cinnamomum zeylanicum were evaluated on some parameters of the life table of the pest, at the constant temperature of 30?°C, relative humidity of 40?±?5% and photoperiod of 16L: 8D. Our results showed that the essential oil of cinnamon is effective on female adult stage. Lethal concentration at which 50% mortality (LC₅₀) for the essential oils is from C. zeylanicum on female adult mite was 23.39?μl/L air. Sublethal concentrations of the essential oil of C. zeylanicum also impair the natural biology of the mite. Concentrations of sublethal of essential oil decreased age-specific fertility (m_x) of T. urticae compared with the control. Sublethal concentrations (LC₁₀ and LC₂₅) have reduced the life expectancy (e_x) in egg stage. Sublethal effects of the essential oil of C. zeylanicum and its impact on T. urticae management are discussed.     

The effect of inorganic and organic pollutants on sperm motility of some freshwater teleosts

Using four different sperm types from brown trout Salmo trutta fario (Salmonidae), chub Leuciscus cephalus (Cyprinidae), burbot Lota lota (Gadidae) and African catfish Clarias gariepinus (Clariidae) the effect of inorganic (cadmium, copper, mercury, lead, zinc and nitrite) and organic (cyclohexane and 2,4‐dichlorophenol) environmental pollutants on sperm motility was investigated. Spermatozoa were activated in double distilled water containing the different test substances and the motility was compared to controls of similar pH. From the investigated motility variables the sperm motility rate and swimming velocity reacted most to the environmental pollutants whereby the changes depended on the species and on the test substance. African catfish spermatozoa were the most resistant, chub and burbot spermatozoa showed medium resistance and brown trout spermatozoa were the most sensitive to the pollutants. With exception of 2,4‐dichlorophenol and zinc the effective concentrations of the tested pollutants exceeded the recommendation for surface waters 100–10·000‐fold and were in a range lethal for the fish themselves. Therefore, it was concluded that fish sperm motility is not a suitable marker for risk assessment of environmental pollutants.     

Preparation of pre-cut corneas from fresh donated whole globes for Descemet’s stripping automated keratoplasty: 3-year results at the Central Eye Bank of Iran

To describe the technique and the results of the preparation of pre-cut corneas for Descemet’s stripping automated endothelial keratoplasty (DSAEK) during a 3-year period at the Central Eye Bank of Iran (CEBI). The method of preparation of pre-cut corneas from donated whole globes at the CEBI is described and the frequency and percentage of pre-cut corneas prepared for DSAEK, between April 2009 and March 2012, are specified. Moreover, post-operative reports are reviewed for any complaints about using pre-cut tissues for DSAEK. Out of the 1,518 donated whole globes appropriate for DSAEK, 1,478 (97.4 %) pre-cut corneas were successfully prepared. The method of preparation failed in 40 (2.6 %) cases. Based on the eye bank post-operative reports, thickness of pre-cut tissues for DSAEK was deemed unacceptable in only 6 (0.4 %) cases prior to surgery; five of these were too thick and one was too thin. Preparation of pre-cut corneas, for DSAEK from donated whole globes, in the CEBI is a safe and easy method, with very good preservation of endothelial cells after the preparation of the pre-cut corneas and reduced risks from corneal manipulation.