In-silico network-based analysis of drugs used against COVID-19: Human well-being study

IntroductionResearchers worldwide with great endeavor searching and repurpose drugs might be potentially useful in fighting newly emerged coronavirus. These drugs show inhibition but also show side effects and complications too. On December 27, 2020, 80,926,235 cases have been reported worldwide. Specifically, in Pakistan, 471,335 has been reported with inconsiderable deaths.Problem statementIdentification of COVID-19 drugs pathway through drug-gene and gene−gene interaction to find out the most important genes involved in the pathway to deal with the actual cause of side effects beyond the beneficent effects of the drugs.MethodologyThe medicines used to treat COVID-19 are retrieved from the Drug Bank. The drug-gene interaction was performed using the Drug Gene Interaction Database to check the relation between the genes and the drugs. The networks of genes are developed by Gene MANIA, while Cytoscape is used to check the active functional association of the targeted gene. The developed systems cross-validated using the EnrichNet tool and identify drug genes'' concerned pathways using Reactome and STRING.ResultsFive drugs Azithromycin, Bevacizumab, CQ, HCQ, and Lopinavir, are retrieved. The drug-gene interaction shows several genes that are targeted by the drug. Gene MANIA interaction network shows the functional association of the genes like co-expression, physical interaction, predicted, genetic interaction, co-localization, and shared protein domains.ConclusionOur study suggests the pathways for each drug in which targeted genes and medicines play a crucial role, which will help experts in-vitro overcome and deal with the side effects of these drugs, as we find out the in-silico gene analysis for the COVID-19 drugs.     

Stability of field-selected resistance to insecticides in Plutella xylostella (Lep., Plutellidae) from Pakistan

Abstract:  To investigate fluctuation in susceptibility to insecticides, natural populations of Plutella xylostella were collected from the same field in the region of Multan, Pakistan, in late summer, mid-winter and early spring. After bulking up for a generation in the laboratory, the populations were examined against pyrethroids and organophosphates as well as newer insecticides (spinosad, indoxacarb and emamectin). Each population showed a broad range of variation in susceptibility to all chemicals. Comparison between populations collected in different times of years in 2003 and 2004 showed variation in susceptibility to organophosphates and pyrethroids. In winter, susceptibility to organophosphates increased, whereas it decreased in relation to pyrethroids. However, susceptibility to the newer insecticides was unchanged within the season. The results suggest that the fluctuation observed in susceptibility could be either associated with fitness costs of organophosphate and pyrethroids or cessation of insecticides. These results might have important implications in resistance management. We propose a strategy for application of insecticides in relation to P. xylostella management in Pakistan.     

Colorization and automated segmentation of human T2 MR brain images for characterization of soft tissues

Characterization of tissues like brain by using magnetic resonance (MR) images and colorization of the gray scale image has been reported in the literature, along with the advantages and drawbacks. Here, we present two independent methods; (i) a novel colorization method to underscore the variability in brain MR images, indicative of the underlying physical density of bio tissue, (ii) a segmentation method (both hard and soft segmentation) to characterize gray brain MR images. The segmented images are then transformed into color using the above-mentioned colorization method, yielding promising results for manual tracing. Our color transformation incorporates the voxel classification by matching the luminance of voxels of the source MR image and provided color image by measuring the distance between them. The segmentation method is based on single-phase clustering for 2D and 3D image segmentation with a new auto centroid selection method, which divides the image into three distinct regions (gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using prior anatomical knowledge). Results have been successfully validated on human T2-weighted (T2) brain MR images. The proposed method can be potentially applied to gray-scale images from other imaging modalities, in bringing out additional diagnostic tissue information contained in the colorized image processing approach as described.     

First report on the molecular prevalence of Mycoplasma capricolum subspecies capripneumoniae (Mccp) in goats the cause of contagious caprine pleuropneumonia (CCPP) in Balochistan province of Pakistan

Contagious caprine pleuropneumonia (CCPP) caused by Mycoplasma capricolum subspecies capripneumoniae (Mccp) is a disease of goats which causes high morbidity and mortality and is reported in many countries of the world. There are probably no reports on the molecular prevalence of Mccp, Mycoplasma capricolum subsp. capricolum (Mcc) and Mycoplasma putrefaciens (Mp) in Balochistan and any other part of Pakistan. Thirty goats (n = 30) with marked respiratory symptoms were selected and procured from forty goat flocks in Pishin district of Balochistan in 2008. The genomic deoxyribonucleic acid (DNA) from the lung samples (n = 30) of the slaughtered goats was purified and subjected to polymerase chain reaction (PCR) assays for the presence of Mycoplasma mycoides cluster members and Mp. The PCR-RFLP (restriction fragment length polymorphism) was also used to further confirm the Mccp. Of the thirty lung samples 17 (56.67%) were positive for the molecular prevalence of Mcc, Mccp and Mp. In total the molecular prevalence was observed as 17.65% for Mccp (n = 3), 70.59% for Mcc (n = 12) and 11.76% for Mp (n = 2). The RFLP profile has also validated the PCR results of Mccp by yielding two bands of 190 and 126 bp. The results of PCR-RFLP coupled with the presence of fibrinous pleuropneumonia and pleurisy during postmortem of goats (n = 3) strongly indicated the prevalence of CCPP in this part of world. Moreover the prevalence of Mcc and Mp is also alarming in the study area. We report for the very first time the molecular prevalence of Mcc, Mccp, and Mp in the lung tissues of goats in the Pishin district of Balochistan, Pakistan.     

Could resistance to insecticides in Plutella xylostella (Lep., Plutellidae) be overcome by insecticide mixtures?

Abstract: To investigate if synergism occurs between pyrethroids, organophosphates and new insecticides, we tested representatives of these compounds (bifenthrin, chlorpyrifos, spinosad, indoxacarb and emamectin) against the diamondback moth (Plutella xylostella). Larvicidal activity of these insecticides was assessed separately and together on a susceptible strain (Lab‐UK) of P. xylostella as well as a field population collected from Multan. The field population showed significant resistance to chlorpyrifos (331 100‐fold), bifenthrin (45 200‐fold), emamectin (1800‐fold), spinosad (11‐fold) and indoxacarb (5600‐fold) when compared with the Lab‐UK population. When insecticides were mixed based on LC₅₀ and tested at serial concentrations against Lab‐UK, significant synergy (CI < 1) occurred between bifenthrin, spinosad and emamectin. In contrast, the interaction between bifenthrin and indoxacarb was additive (CI = 1). The toxicity of bifenthrin against the field population increased significantly (P < 0.01) when combined with spinosad, emamectin and indoxacarb. Synergistic effects could be attributed to the complementary modes of action by these insecticide classes acting on different components of nerve impulse transmission (which are not identical for bifenthrin and indoxacarb either). However, chlorpyrifos/bifenthrin mixture was not significantly different either from bifenthrin or chlorpyrifos alone, indicating an additive affect. In combination with spinosad and emamectin, tested against the resistant field population, the toxicity of chlorpyrifos increased significantly and even more so with indoxacarb. Mixtures could also give rise to multiple resistance that may extend across other chemical classes and thus become difficult to manage. Therefore, alternative strategies such as mosaics or rotations should be considered. That is, though synergistic effects have been found, this should not be followed up as a strategy to manage resistant field populations.     

Evidence for resistance to pyrethroids and organophosphates in Plutella xylostella (Lepidoptera: Plutellidae) from Pakistan

The susceptibility of representative pyrethroid (cypermethrin, deltamethrin, lambdacyhalothrin, bifenthrin), organophosphate (chlorpyriphos, triazophos, profenophos) and new chemistry insecticides (spinosad, indoxacarb and emamectin) was investigated for 18 field populations of Plutella xylostella (Linnaeus) from three different zones in Pakistan. The LC(50) (mg ml(-1); 48 h) values of pyrethroids for various populations ranged from 0.19-1.88 for cypermethrin, 0.31-2.64 for deltamethrin, 0.08-1.16 for lambdacyhalothrin and 0.07-0.88 for bifenthrin. The LC(50) (mg ml(-1); 48 h) of organophosphates ranged from 0.52-5.67 for chlorpyriphos, 0.37-4.14 for triazophos and 0.03-2.65 for profenophos. The most probable reason for low toxicity of organophosphates and pyrethroids is the evolution of multiple resistance mechanisms; however, further studies are required to establish these mechanisms. When these same products were tested against a susceptible laboratory population (Lab-Pak), the new chemistry compounds were significantly more toxic than pyrethroids and organophosphates. The results are discussed in relation to integrated pest management and insecticide resistance management strategies for P. xylostella.