Flufenamic acid is a tool for investigating TRPC6-mediated calcium signalling in human conditionally immortalised podocytes and HEK293 cells

Mutations in the cation channel TRPC6 result in a renal-specific phenotype of familial nephrotic syndrome, affecting intracellular calcium ([Ca²⁺]_i) signalling in the glomerular podocyte. Tools to study native TRPC6 activity are scarce, although there has been recent success with flufenamic acid (FFA). We confirm the specificity of FFA for TRPC6 both in an artificial expression system and in a human conditionally immortalised podocyte cell line (ciPod).Cells were loaded with fura-2AM and changes in intracellular calcium ([Ca²⁺]_i) were calculated. 200 μM FFA induced an increase in [Ca²⁺]_i in HEK293 cells with native TRPC6 expression, which was enhanced by overexpression of TRPC6 and completely blocked in the absence of extracellular calcium. Expressed TRPC7 did not significantly affect the response to FFA whereas expressed TRPC3 reduced it. FFA also induced an increase ciPod in [Ca²⁺]_i, which was inhibited using SKF96365 and 2-APB, but not indomethacin. In ciPod, adenovirus (Ad-v) wild type (WT) TRPC6 increased [Ca²⁺]_i activity to FFA compared to native TRPC6, whereas activity was significantly reduced with Ad-v dominant negative (DN) TRPC6. The niflumic acid (NFA) induced increase in [Ca²⁺]_i in ciPod was not affected by Ad-v TRPC6 DN, and in HEK293 cells was not affected by WT TRPC6.In conclusion, FFA activates TRPC6 [Ca²⁺]_i signalling in both ciPod and HEK293 cells independently of TRPC3 and TRPC7, and independently of properties of the fenamate family.     

Estimation of Toxic Metals in Scalp Hair Samples of Chronic Kidney Patients

The determination of toxic metals (TMs) in the biological samples of human beings is an important clinical screening procedure. The aim of this work is to determine total content of TMs, aluminum (Al), cadmium (Cd), nickel (Ni), and lead (Pb) in scalp hair samples of chronic kidney male patients (CKPs) on maintenance hemodialysis, during the period of 2005–2007. The study included 115 CKPs (all smokers) and 150 controls or referents [82 (nonsmokers) and 68 (smokers)]. Both controls and patients (males) were of the same age group (ranged 25–55 years), socioeconomic status, localities, and dietary habits. The scalp hair samples were analyzed by electrothermal atomic absorption spectrometer, prior to microwave-induced acid digestion. The accuracy of the total Al, Cd, Ni, and Pb measurements was tested by simultaneously analyzing certified reference material (human hair NCS ZC81002). No significant differences were observed between the analytical results and the certified values (paired t test at p > 0.05). The levels of TMs in scalp hair samples of patients were found to be higher as compared to control nonsmoker and smokers. Moreover, the study shows that levels of Al, Cd, Ni, and Pb in scalp hair samples may be useful to evaluate the impact of cigarette smoking in kidney failure patients.     

Effect of weather factors on populations of Helicoverpa armigera moths at cotton-based agro-ecological sites

Pheromone trapping was used to monitor populations of the moth Helicoverpa armigera at five cotton‐based agro‐ecological sites – river, vegetable, orchard, forest and clean cultivation (areas under only cotton cultivation) – in the Bahawalpur district, Pakistan. Three locations at each site were chosen and three pheromone traps at each location were installed in cotton fields. Moth catches were recorded at 15–20 day intervals from 24 October 2004 to 19 December 2006. In 2004, the river sites showed the maximum trapped population of H. armigera (0.22/trap) followed by 0.165 per trap at the vegetable sites. Orchard, clean cultivation and forest sites had zero moth catches. In 2005, the river sites again showed the highest trapped population (0.57/trap), followed by clean cultivation (0.45/trap), vegetable (0.44/trap), orchard (0.40/trap) and forest (0.29/trap). The moths appeared during July to December and March to May. In 2006, sites showed non‐significant difference, with a population range of 0.47 to 0.97 moths per trap. On average, river sites peaked at 0.49 per trap, followed by vegetable (0.38), clean cultivation (0.47), orchard (0.35) and forest (0.25) sites. The peak was observed on 3 April 2006, and moths appeared during February to July and October to December. The minimum temperature in river, forest and clean cultivation sites; the maximum temperature in orchard sites; and the average temperature in river, orchard, forest and clean cultivation sites showed significant positive correlations with trapped moth populations. Relative humidity showed significant negative correlation with population at the orchard sites in 2005. All weather factors during 2004 and 2006 showed non‐significant correlations with the moth populations. No model was found to be best fit by multiple linear regression analysis; however, relative humidity, minimum temperature, maximum temperature, minimum temperature and maximum temperature contributed 8.40, 10.23, 2.43, 4.53 and 2.53% to the population fluctuation of the moth at river, vegetable, orchard, forest and clean cultivation sites, respectively.     

Influence of weather on the moth catches of Helicoverpa armigera at various cotton-based agro-ecological sites

Pheromones are innate products, exploited for direct population manipulation in the trapping of precise pest density. They demonstrate feasibility and efficiency against Helicopverpa armigera at five different cotton-based agro-ecological sites: river site, vegetable farm, orchard, clean cultivation site, and forest. The data were recorded at 15–20 day intervals from 8 September 2004 to 1 December 2006. The Number of moths caught during the study period demonstrated that the vegetable farm showed the maximum population of moths per trap (0.54), followed by the orchard (0.29), forest (0.19), river (0.15), and clean cultivation site (0.12). During 2004, rainfall (in the orchard and clean cultivation site) and relative humidity (in the clean cultivation site) showed positive and significant correlation with the number of moths caught. During 2005, temperatures played a significant and positive role in population fluctuation of the pest almost at all the selected sites; the minimum temperature was recorded at the vegetable farm and the average temperature was found at the forest site. Rainfall also showed a significant and positive correlation with trapped moths in the vegetable farm, orchard, and clean cultivation site. During 2006, relative humidity showed a significant and negative correlation with the trapped population at all the sites except the river site. Rainfall showed a negative and significant correlation with the pest at the forest site. Relative humidity was the most important aspect at 8.93% causing variation in the trapped population followed by maximum temperature (5.7%), rainfall (1.63%), average temperature (0.74%), and minimum temperature (0.56%).     

Ethnobotanical studies of plants of Charkotli Hills, Batkhela District, Malakand, Pakistan

A survey was conducted with the aim to document the indigenous information of Charkotli Hills, Batkhela District, Malakand, Pakistan. The area has rich vegetation and a high potential for ethnobotanical utiliza-tion. Information was collected on various traditional uses of 100 plants distributed over 49 families, of which 43 families were of dicot, 2 of monocot, 2 of pteridophyta, and 1 of gymnosperms. Most plants have more than one local use. Sixty-six plants were found to be medicinal species, 21 fruit and edible seed species, 11 furniture species, 18 fodder or forage species, 12 vegetable species, 12 fuel species, 11 thatching and building species, 5 hedge or fencing species, 5 timber wood species, 5 poisonous plants, 3 species used in ketchup, 2 fixed oil yielding species, 2 miswak species, 2 species for making sticks for cattle and defense purposes, 2 species cultivated for ornamental purposes, 2 species used as mehindi by girls, 1 irritant species, 1 species for the making of Salai (a little stick for applying 'surma' to the eyes), 1 species for tanning, 1 species used as refresher in milk pots, 1 species giving gum used as chewing gum, and 1 species used as insect repellent. The area is under heavy pressure of deforestation and overgrazing, which have reduced the regeneration of woody plants. Proper ecological manage-ment is required to protect the wildlife and ethnobotanical resources for the coming generations.     

Understanding Physiological and Degenerative Natural Vision Mechanisms to Define Contrast and Contour Operators

Background

Dynamical systems like neural networks based on lateral inhibition have a large field of applications in image processing, robotics and morphogenesis modeling. In this paper, we will propose some examples of dynamical flows used in image contrasting and contouring.

Methodology

First we present the physiological basis of the retina function by showing the role of the lateral inhibition in the optical illusions and pathologic processes generation. Then, based on these biological considerations about the real vision mechanisms, we study an enhancement method for contrasting medical images, using either a discrete neural network approach, or its continuous version, i.e. a non-isotropic diffusion reaction partial differential system. Following this, we introduce other continuous operators based on similar biomimetic approaches: a chemotactic contrasting method, a viability contouring algorithm and an attentional focus operator. Then, we introduce the new notion of mixed potential Hamiltonian flows; we compare it with the watershed method and we use it for contouring.

Conclusions

We conclude by showing the utility of these biomimetic methods with some examples of application in medical imaging and computed assisted surgery.     

Lecanicillium and Verticillium species from Indonesia and Japan including three new species

Forty-six Lecanicillium strains and one Verticillium strain were isolated from subterranean and epiphytic arthropods, soil, and other sources collected in Indonesia and Japan. These strains were identified as nine Lecanicillium and one Verticillium species including six undescribed species based on light microscopy and the sequences of the ITS-1 and ITS-2 regions including 5.8S ribosomal DNA. Four of the ten species (L. araneicola, L. kalimantanense, Lecanicillium sp. 4, and V. indonesiacum) were recovered from Indonesia, five of the ten (L. attenuatum, L. fusisporum, L. psalliotae, Lecanicillium sp. 1, and Lecanicillium sp. 3) were from Japan, and L. saksenae was from both countries. In this article, new species (L. araneicola, L. kalimantanense, and V. indonesiacum) and a new combination (L. saksenae) are proposed from the fungi isolated from epiphytic and subterranean arthropods collected in East Kalimantan.     

Elucidation of binding mode and three dimensional quantitative structure–activity relationship studies of a novel series of protein kinase B/Akt inhibitors

Protein kinase B (PKB; also known as Akt kinase) is located downstream in the PI-3 kinase pathway. Overexpression and constitutive activation of PKB/Akt leads to human prostate, breast and ovarian carcinomas. A series of 69 PKB/Akt inhibitors were examined to explore their binding modes using FlexX, and three-dimensional quantitative structure–activity relationship (3D-QSAR) studies based on comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed to provide structural insights into these compounds. CoMFA produced statistically significant results, with cross-validated q ² and non-cross validated correlation r ² coefficients of 0.53 and 0.95, respectively. For CoMSIA, steric, hydrophobic and hydrogen bond acceptor fields jointly yielded ‘leave one out’ q ²  = 0.51 and r ²  = 0.84. The predictive power of CoMFA and CoMSIA was determined using a test set of 13 molecules, which gave correlation coefficients, of 0.58 and 0.62, respectively. Molecular docking revealed that the binding modes of these molecules in the ATP binding sites of the Akt kinase domain were very similar to those of the co-crystallized ligand. The information obtained from 3D contour maps will allow the design of more potent and selective Akt kinase inhibitors.     

Decolorization of practical textile industry effluents by white rot fungus Coriolus versicolor IBL-04

Textile industry discharges a vast amount of unused synthetic dyes in effluents. The discharge of these effluents into rivers and lakes leads to a reduction in sunlight penetration in natural water bodies, which, in turn, decreases both photosynthetic activity and dissolved oxygen concentration rendering it toxic to living beings. This paper describes the decolorization potential of a local white rot fungus, Coriolus versicolor IBL-04 for practical industrial effluents collected from five different textile industries of Faisalabad, Pakistan. Screening of C. versicolor IBL-04 on five effluents showed best decolorization results (36.3%) for Arzoo Textile Industry (ART) effluent in 6 days followed by Crescent Textile Industry (CRT), Itmad Textile Industry (ITT), Megna Textile Industry (MGT) and Ayesha Textile Industry (AST) effluents. Optimization of different process parameters for ART effluent decolorization by C. versicolor IBL-04 showed that manganese peroxidase (MnP) (486 U/mL) was the lignolytic enzyme present in the culture filtrates with undetectable lignin peroxidase (LiP) and laccase. The MnP synthesis and effluent decolorization could be enhanced to 725 U/mL and 84.4%, respectively, with a significant time reduction to 3 days by optimizing pH and temperature and using 1% starch as a supplementary carbon source.     

Synthesis and antibacterial activity of substituted flavones, 4-thioflavones and 4-iminoflavones

Synthesis of flavones, 4-thioflavones and 4-iminoflavones was carried out with the substitution of variable halogens, methyl, methoxy and nitro groups in the A, B and AB rings of the respective compounds and we also report here their antibacterial activity. Most of the synthesized compounds were found to be active against Escherichia coli, Bacillus subtilis, Shigella flexnari, Salmonella aureus, Salmonella typhi and Pseudomonas aeruginosa. Activity of 4-thioflavones and 4-iminoflavones was found to be higher than that of their corresponding flavone analogues. Investigated compounds having substituents like F, OMe and NO2 at 4'-position in ring-B exhibited enhanced activity and the presence of electronegative groups in the studied compounds showed a direct relationship to the antibacterial activity.