Increased food utilization indices and decreased proteolytic activity in Helicoverpa armigera larvae fed sublethal Bacillus thuringiensis‐treated diet

The cotton bollworm Helicoverpa armigera is one of the most devastating insect pests. A set of protease enzymes allows this species to feed on different host plant species. Control measures in agriculture often involve the application of the pathogenic bacterium Bacillus thuringiensis subsp. kurstaki (Btk). In the present study, the effects of sublethal Btk doses are evaluated with respect to the food utilization indices and proteolytic activities of Helicoverpa armigera. Accordingly, the H. armigera larvae are fed with artificial diet containing sublethal Btk doses (LC₅, LC₁₀, LC₁₅, LC₂₀ and LC₂₅) and a Btk‐free diet as control. All but one of the food utilization indices we measured is observed to increase significantly with increasing Btk doses. By contrast, the specific activity of total protease, chymotrypsin and elastase enzymes decrease significantly with an increasing Btk concentration. We conclude that Btk was not toxic to H. armigera larvae and any damage that it causes can be compensated for by H. armigera larvae via various mechanisms. In conclusion, increased nutritional indices in the larvae fed with Btk diet represent an important issue that needs to be considered to avoid the pest establishing Bt resistant populations. Meanwhile, the lack of effect of Btk sublethal concentrations on trypsin enzyme specific activity can bolster this challenge.     

Renal impairment and analgesia: From effectiveness to adverse effects

Kidney pain is one of the clinically significant features of renal dysfunction. Mild to severe pain is seen in the lower back area. Painkillers are mostly recommended in these cases to relieve the symptom. Yet, several analgesics are associated with side effects that can worsen the state of the disease. This review is based on the studies conducted in these aspects analgesics used to treat kidney pain and their effectiveness, renal consequences of postoperative analgesia, and pharmacogenetics of these palliatives are briefly summarized in this paper.     

Cardioprotective role of extracellular vesicles: A highlight on exosome beneficial effects in cardiovascular diseases

Extracellular vesicles (EVs) are nano-sized vesicles, released from many cell types including cardiac cells, have recently emerged as intercellular communication tools in cell dynamics. EVs are an important mediator of signaling within cells that influencing the functional behavior of the target cells. In heart complex, cardiac cells can easily use EVs to transport bioactive molecules such as proteins, lipids, and RNAs to the regulation of neighboring cell function. Cross-talk between intracardiac cells plays pivotal roles in the heart homeostasis and in adaptive responses of the heart to stress. EVs were released by cardiomyocytes under baseline conditions, but stress condition such as hypoxia intensifies secretome capacity. EVs secreted by cardiac progenitor cells and cardiosphere-derived cells could be pinpointed as important mediators of cardioprotection and cardiogenesis. Furthermore, EVs from many different types of stem cells could potentially exert a therapeutic effect on the damaged heart. Recent evidence shows that cardiac-derived EVs are rich in microRNAs, suggesting a key role in the controlling of cellular processes. EVs harboring exosomes may be clinically useful in cell-free therapy approaches and potentially act as prognosis and diagnosis biomarkers of cardiovascular diseases.     

Modulation of the immune response by Middle East respiratory syndrome coronavirus

Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells.     

4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide (CMH) targets mRNA of the c-FLIP variants and induces apoptosis in MCF-7 human breast cancer cells

Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) is a major resistance factor for the tumor necrosis factor-related apoptosis-inducing ligand TRAIL and in drug resistance in human malignancies. c-FLIP is an antagonist of caspases-8 and -10, which inhibits apoptosis and is expressed as long (c-FLIP_L) and short (c-FLIP_S) splice forms. c-FLIP is often overexpressed in various human cancers, including breast cancer. Several studies have shown that silencing c-FLIP by specific siRNAs sensitizes cancer cells to TRAIL and anticancer agents. However, systemic use of siRNA as a therapeutic agent is not practical at present. In order to reduce or inhibit c-FLIP expression, small molecules are needed to allow targeting c-FLIP without inhibiting caspases-8 and -10. We used a small molecule inhibitor of c-FLIP, 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide (CMH), and show that CMH, but not its inactive analog, downregulated c-FLIP_L and c-FLIP_S mRNA and protein levels, caused poly(ADP-ribose) polymerase (PARP) degradation, reduced cell survival, and induced apoptosis in MCF-7 breast cancer cells. These results revealed that c-FLIP is a critical apoptosis regulator that can serve as a target for small molecule inhibitors that downregulate its expression and serve as effective targeted therapeutics against breast cancer cells.     

Genetic analysis of reactivity to humans in Goettingen minipigs

Goettingen minipigs are laboratory animals with an increasing demand over the last few years. At the moment, Goettingen minipigs are not selected for a low reactivity to humans and this trait is not included in the breeding programme. However, it is obvious that there is a need for genetically non-responding minipigs during handling to facilitate the treatment and restraint of the animals which is often needed in biomedical experiments. A first testing scheme was developed to evaluate the reactivity of Goettingen minipigs to humans and to analyse whether the trait reactivity to humans can be considered in the breeding programme. In this study temperament scores of this testing scheme for nine different traits from 10,033 animals collected from 2005 to 2008 were analysed. Temperament was subjectively scored on a scale from 1 to 5 while the pig is caught (C), held on the arms (A), standing in a box for weighing (W), standing on a table (T) and walking on the ground (G). The traits were a combination of these situations evaluated at three different ages (2, 4 and 6 months). Genetic parameters were estimated using bivariate models and different possible selection strategies were examined. Heritabilities were low to moderate with a range from 0.09 to 0.22 and phenotypic and genetic correlations between the nine traits were moderate to high with phenotypic correlations between 0.12 (W2 and G4) and 0.64 (W2 and A2) and genetic correlations between 0.44 (A4 and C6) and 1.00 (e.g. W2 and A4). It was shown that the highest genetic progress per year can be obtained when all nine traits are considered in the selection index. Under an economical point of view the selection on the basis of the two arm traits plus the trait W2 should be preferred.Based on a critical discussion of the explanatory power of the used scoring system a new evaluation scheme was developed. In this scheme the minipigs can be divided into responding and non-responding animals whereas the latter are desired for selection. The suggested scoring system offers better possibilities for statistical analyses. It is planned to include the selection for non-responding Goettingen minipigs in the routine breeding programme.     

A computational model of the human left-ventricular epicardial myocyte

A computational model of the human left-ventricular epicardial myocyte is presented. Models of each of the major ionic currents present in these cells are formulated and validated using experimental data obtained from studies of recombinant human ion channels and/or whole-cell recording from single myocytes isolated from human left-ventricular subepicardium. Continuous-time Markov chain models for the gating of the fast Na(+) current, transient outward current, rapid component of the delayed rectifier current, and the L-type calcium current are modified to represent human data at physiological temperature. A new model for the gating of the slow component of the delayed rectifier current is formulated and validated against experimental data. Properties of calcium handling and exchanger currents are altered to appropriately represent the dynamics of intracellular ion concentrations. The model is able to both reproduce and predict a wide range of behaviors observed experimentally including action potential morphology, ionic currents, intracellular calcium transients, frequency dependence of action-potential duration, Ca(2+)-frequency relations, and extrasystolic restitution/post-extrasystolic potentiation. The model therefore serves as a useful tool for investigating mechanisms of arrhythmia and consequences of drug-channel interactions in the human left-ventricular myocyte.     

The removal of ρ-chlorophenol in aqueous cultures with free and alginate-immobilized cells of the microalga Tetraselmis suecica

The present study aimed at evaluating the ability of some isolated cyanobacterial and microalgal strains for the removal of ρ-chlorophenol (ρ-CP), an environmentally harmful contaminant. To identify the most efficient species, a screening program was carried out using 15 microalgal and cyanobacterial strains. Among them, Tetraselmis suecica was able to remove 67 % of the ρ-chlorophenol at an initial concentration of 20 mg L^?1 from the medium within a 10-day period. The efficacy of the process was dependent on the ρ-chlorophenol concentration. At concentrations above 60 mg L^?1 of the pollutant, no removal was observed due to the inhibitory effect of ρ-chlorophenol on the T. suecica cells. The effect of cell immobilization in alginate beads on T. suecica removal capacity was also examined. Using this technique, the removal efficacy for the initial ρ-CP concentration of 20 mg L^?1 increased up to 94 %.