Serological,Molecular and Entomological Surveillance Demonstrates Widespread Circulation of West Nile Virus in Turkey

West Nile virus (WNV), a mosquito-borne flavivirus with significant impact on human and animal health, has recently demonstrated an expanded zone of activity globally. The aim of this study is to investigate the frequency and distribution of WNV infections in potential vectors and several mammal and avian species in Turkey, where previous data indicate viral circulation. The study was conducted in 15 provinces across Turkey during 2011–2013. In addition, the entomological study was extended to 4 districts of the Turkish Republic of Northern Cyprus. WNV exposure was determined in humans, horses, sheep and ducks from Mersin, Sanliurfa, Van and Kars provinces of Turkey, via the detection of neutralizing antibodies. WNV RNA was sought in human and equine samples from Mersin, Adana and Mugla provinces. Field-collected mosquitoes from 92 sites at 46 locations were characterized morphologically and evaluated for viral RNA. Neutralizing antibodies were identified in 10.5% of the 1180 samples studied and detected in all species evaluated. Viral nucleic acids were observed in 5.9% of 522 samples but only in horses. A total of 2642 mosquito specimens belonging to 15 species were captured, where Ochlerotatus caspius (52.4%), Culex pipiens sensu lato (24.2%) comprise the most frequent species. WNV RNA was detected in 4 mosquito pools (1.9%), that comprise Oc. caspius Cx. pipiens s.l. and DNA barcoding revealed the presence of Cx. quinquefasciatus and Cx. perexiguus mosquitoes in infected Culex pools. All WNV partial sequences were characterized as lineage 1 clade 1a. These findings indicate a widespread WNV activity in Turkey, in Eastern Thrace and Mediterranean-Aegean regions as well as Southeastern and Northeastern Anatolia.     

4-Phenylbutyric Acid Plus Valproic Acid Exhibits the Therapeutic and Neuroprotective Effects in Acute Seizures Induced by Pentylenetetrazole

Neurochemical Research - Endoplasmic reticulum (ER) stress and apoptosis are implicated in the pathogenesis of epilepsy. Here we examine the effects of valproic acid (VA) plus 4-phenylbutyric acid...     

Signal responsiveness of IkappaB kinases is determined by Cdc37-assisted transient interaction with Hsp90

The IkappaB kinase (IKK) holocomplex, containing the kinases IKKalpha, IKKbeta, and the scaffold NEMO (NF-kappaB essential modifier), mediates activation of NF-kappaB by numerous physiological stimuli. Heat shock protein 90 (Hsp90) and the co-chaperone Cdc37 have been indicated as additional subunits, but their specific functions in signal transduction are indistinct. Using an RNA interference approach, we demonstrate that Cdc37 recruits Hsp90 to the IKK complex in a transitory manner, preferentially via IKKalpha. Binding is conferred by N-terminal as well as C-terminal residues of Cdc37. Cdc37 is essential for the maturation of de novo synthesized IKKs into enzymatically competent kinases but not for assembly of an IKK holocomplex. Mature IKKs, T-loop-phosphorylated after stimulation either by receptor-mediated signaling or upon DNA damage, further require Hsp90-Cdc37 to generate an activated state. Thus, the present data denote Hsp90-Cdc37 as a transiently acting essential regulatory component of IKK signaling.     

Reverse Logistics Network Design under the Risk of Hazardous Materials Transportation

ABSTRACT

An effective reverse logistics network design (RLND) has several implications, such as decrease in logistics costs and environmental damage. Some products in the RL may contain hazardous substances. In such cases, the environmental aspects of RLND should be identified considering the risks of hazardous materials transportation.

In this study, a holistic approach is employed involving the forecasting of return amount of products, risk modeling of hazardous materials transportation, and capacitated plant location modeling under risk. An application for the reverse logistics of large household appliances in Turkey, which is aiming to implement the European Union directive for waste electric and electronic equipment, is presented. First, the decisions of suitable places for treatment facilities and the assignments of the returned products to these facilities are made without considering the risk factor. In this case, the objective is to minimize the total logistics costs. In the second case, risk factors are incorporated in the model and the objective is defined as the minimization of the costs and hazmat transportation risks. It is seen that different locations and allocation decisions are obtained for the case without considering the risk and the case under risk of hazmat transportation.     

A very simple high‐performance liquid chromatographic method with fluorescence detection for the determination of gemifloxacin in human breast milk

A high‐performance liquid chromatographic method with fluorescence detection was developed and validated for the determination of gemifloxacin in human breast milk. The proposed method allows the determination of gemifloxacin in breast milk samples without complex sample preparation. The samples were mixed with a mobile phase and filtered with a 0.45 µm polytetrafluoroethylene filter before analysis. Chromatographic separation was carried out on a C18 column (150 × 4.6 mm, 5 µm I.D.) using methanol:50 mM ortho‐phosphoric acid solution (40:60) as the mobile phase with a 1.0 mL/min flow rate. Quantitation was performed using fluorescence detection with an excitation wavelength at 272 nm and an emission wavelength at 395 nm. The linear range was found to be 0.1–2.5 µg/mL. The method was applied successfully for the determination of gemifloxacin in breast milk obtained from a breastfeeding mother after oral administration of a single tablet that included 320 mg gemifloxacin per gemifloxacin tablet. Copyright © 2015 John Wiley & Sons, Ltd.     

Optimization of citric acid production from a carrot juice-based medium by <Emphasis Type="Italic">Yarrowia lipolytica</Emphasis> using response surface methodology

In this study, diluted and fortified carrot juice was used for modelling and optimization of citric acid production by a new mutant strain, Yarrowia lipolytica K-168. Protein concentrate obtained from fine flour -a byproduct of semolina production- was used as a nitrogen source in the fermentation medium. Interactive effects of selected independent variables, initial total sugar concentration, initial pH, initial concentration of protein concentrate obtained from fine flour of semolina and temperature, on the growth and citric acid production of the yeast were investigated. An experimental design including 30 experiments was conducted by using the method of central composite design. Modelling the effects of these independent variables on maximum citric acid concentration, maximum citric acid production rate, citric acid yield, the ratio of maximum citric acid concentration to maximum isocitric acid concentration and specific growth rate were performed by response surface methodology. The variations of all of the responses with the independent variables were defined by a quadratic model. Numeric optimization was performed by using the desireability function. The conditions with 190.83 g/L initial sugar concentration, 5.90 initial pH, 0.07 g/L initial concentration of fine flour protein concentrate and 27.86 °C were determined as optimal conditions for citric acid production. The maximum citric acid concentration reached to 80.53 g/L in optimal conditions.     

A Network Biology Approach to Denitrification in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a metabolically flexible member of the Gammaproteobacteria. Under anaerobic conditions and the presence of nitrate, P. aeruginosa can perform (complete) denitrification, a respiratory process of dissimilatory nitrate reduction to nitrogen gas via nitrite (NO₂), nitric oxide (NO) and nitrous oxide (N₂O). This study focuses on understanding the influence of environmental conditions on bacterial denitrification performance, using a mathematical model of a metabolic network in P. aeruginosa. To our knowledge, this is the first mathematical model of denitrification for this bacterium. Analysis of the long-term behavior of the network under changing concentration levels of oxygen (O₂), nitrate (NO₃), and phosphate (PO₄) suggests that PO₄ concentration strongly affects denitrification performance. The model provides three predictions on denitrification activity of P. aeruginosa under various environmental conditions, and these predictions are either experimentally validated or supported by pertinent biological literature. One motivation for this study is to capture the effect of PO₄ on a denitrification metabolic network of P. aeruginosa in order to shed light on mechanisms for greenhouse gas N₂O accumulation during seasonal oxygen depletion in aquatic environments such as Lake Erie (Laurentian Great Lakes, USA). Simulating the microbial production of greenhouse gases in anaerobic aquatic systems such as Lake Erie allows a deeper understanding of the contributing environmental effects that will inform studies on, and remediation strategies for, other hypoxic sites worldwide.     

In vitro and in silico studies of nitrobenzamide derivatives as potential anti-neuroinflammatory agents

Communicated by Ramaswamy H. Sarma     

Immunoregulatory effects of human dental pulp-derived stem cells on T cells: comparison of transwell co-culture and mixed lymphocyte reaction systems

BACKGROUND AIMS. Studies performed using human and animal models have indicated the immunoregulatory capability of mesenchymal stromal cells in several lineages. We investigated whether human dental pulp-derived stem cells (hDP-SC) have regulatory effects on phytohemagglutinin (PHA)-activated CD3(+) T cells. We aimed to define the regulatory mechanisms associated with hDP-SC that occur in mixed lymphocyte reaction (MLR) and transwell systems with PHA-CD3(+) T cells and hDP-SC at a ratio of 1:1. METHODS. Proliferation, apoptosis and pro- and anti-inflammatory cytokines of PHA-CD3(+)T cells, the expression of Regulatory T cells (Treg) markers and some regulatory factors related to hDP-SC, were studied in Both transwell and MLR are co-cultures systems. RESULTS. Anti-proliferative and apoptotic effects of hDP-SC were determined in co-culture systems. Elevated expression levels of human leukocyte antigen (HLA)-G, hepatocyte growth factor (HGF)-β1, intracellular adhesion molecule (ICAM-1)-1, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β1, vascular adhesion molecule (VCAM)-1 and vascular endothelial growth factor (VEGF) by hDP-SC were detected in the co-culture systems. We observed decreased expression levels of pro-inflammatory cytokines [interferon (IFN)-γ, IL-2, IL-6 receptor (R), IL-12, Interleukin-17A (IL-17A), tumor necrosis factor (TNF)-α] and increased expression levels of anti-inflammatory cytokine [inducible protein (IP)-10] from PHA-CD3(+) T cells in the transwell system. Expression of Treg (CD4(+) CD25(+) Foxp3(+)) markers was significantly induced by hDP-SC in both co-culture systems. We observed apoptosis of PHA-CD3(+) T cells with 24 h using time-lapse camera photographs and active caspase labeling; it is likely that paracrine soluble factors and molecular signals secreted by hDP-SC led this apoptosis. CONCLUSIONS. We suggest that hDP-SC have potent immunoregulatory functions because of their soluble factors and cytokines via paracrine mechanisms associated with PHA-CD3(+) T cells, which could contribute to clinical therapies.