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This paper investigates the discourse of public hanging of rapists on the social media space, that is, Twitter in Pakistan. It also examines how this discourse is interdiscursively related to the power relations particularly implicated in the discourses on religion and gender and the possible effects of this discursive struggle on society. By employing Critical Discourse Analysis (CDA) for analysis, this research uses Laclau and Mouffe’s Discourse Theory as theoretical framework. We conclude that the discourse approving death by hanging for the rapists is a device to propagate the power and the fear of the State. It has a “repetition induced effect” and implies sovereign’s exception; and women are silenced in their demands for justice against the patriarchal social structures which are responsible for crime against women’s body. It also reifies the patriarchal structures and controls societies through vengeance rather than reformative justice.

Despite being intertwined by geographical, linguistic, regional, religious and ethnic knots, Pakistan and Afghanistan have experienced upheavals in their bilateral relations. Changing regional and international political interests have further complicated their relations. Besides confronting traditional security challenges, Pakistan and Afghanistan are facing a severe non-traditional security threat, i.e., the issue of shared waters without any regulatory mechanism. Despite efforts of international organizations in the past, both countries have failed to reach an agreement over the shared waters. Currently, they are following a unilateral water strategy. Afghanistan-India joint water projects further complicate the situation as Pakistan is already facing issues with the latter due to the increasing number of Indian projects on western rivers. Though water may be critical for the recovery of Afghanistan's agriculture based economy, the projects on Kabul River may have serious implications on downstream irrigation and initiatives, the ecology and bilateral relations between the two riparian countries, Pakistan and Afghanistan. Linked closely to the conflicts among states and societies, water as an environmental security issue must be dealt with the same urgency as traditional security challenges. This paper analyzes the security perceptions in Pakistan and Afghanistan and contends that the probability of a future conflict over shared water has not been duly attended. There is a need to develop an integrated mechanism based on the fundamental principle of benefit-sharing instead of dividing waters or any unilateral decisions.

The estrogen receptor 1 gene ( ESR1 ) plays a crucial role in breast and mammary development in humans. Alterations such as gene amplification, genomic rearrangements, and missense mutations in the ESR1 gene are reported to increase the risk of breast cancer in humans. The purpose of this study is to analyze the missense mutations and molecular modeling of ESR1 , focusing on the pathogenic SNP H516N, for a better understanding of disease risk and future benefits for therapeutic benefits. This SNP was selected based on its location in the binding pocket of ESR1 and its predicted impact on drug binding. The in silico analysis was performed by applying various computational approaches to identify highly pathogenic SNPs in the binding pocket of ESR1. The effect of the SNP was explored through docking and intra-molecular interaction studies. All SNPs in ESR1 were identified followed by the identification of the highly pathogenic variant located in the binding pocket of ESR1. The mutant model of the pathogenic SNP H516N was generated, and hydroxytamoxifen was docked with the wild-type and the mutant model. The mutant model lost the formation of stable hydrogen bonds with the active site residues and hydroxytamoxifen, which may result in reduced binding affinity and therefore, will predict the patient's response to estrogenic inhibitors., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ahmad M. Alamri reports financial support was provided by 10.13039/501100007446King Khalid University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Alkannin is a plant-derived naphthoquinone that is isolated from the Boraginaceae family plants. In our previous studies, we found that shikonin, which is the R -enantiomer of alkannin, has potent antidiabetic activity by inhibiting the action of the aldose reductase (AR) enzyme and the protein-tyrosine phosphatase 1B (PTP1B). Therefore, in this study, we aim to explore the antidiabetic effect of alkannin targeting PTP1B and AR by employing in silico and in vitro techniques. For in silico , we used different parameters such as ADMET analysis, molecular docking, MD simulation, Root Mean Square Deviation (RMSD), protein-ligand mapping, and free binding energy calculation. The in vitro evaluation was done by assessing the inhibitory activity and enzyme kinetics of PTP1B and AR inhibition by alkannin. The in silico studies indicate that alkannin possesses favorable pharmacological properties and possesses strong binding affinity for diabetes target proteins. Hydrogen bonds (Val297, Ala299, Leu300, and Ser302) and hydrophobic interactions (Trp20, Val47, Tyr48, Trp79, Trp111, Phe122, Trp219, Val297, Cys298, Ala299, Leu300, and Leu301) are established by the compound, which potentially improves specificity and aids in the stabilization of the protein-ligand complex. The results from in vitro studies show a potent dose-dependent PTP1B inhibitory activity with an IC 50 value of 19.47 μM, and toward AR it was estimated at 22.77 μM. Thus, from the results it is concluded that a low IC 50 value of alkannin for both PTP1B and AR along with favorable pharmacological properties and optimal intra-molecular interactions indicates its utilization as a potential drug candidate for the management of diabetes and its end complications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Diabetes mellitus (DM) is a prominent contributor to morbidity and mortality in developed nations, primarily attributable to vascular complications such as atherothrombosis occurring in the coronary arteries. Aldose reductase (ALR2), the main enzyme in the polyol pathway, catalyzes the conversion of glucose to sorbitol, leading to a significant buildup of reactive oxygen species in different tissues. It is therefore a prime candidate for therapeutic targeting, and extensive study is currently underway to discover novel natural compounds that can inhibit it. Cucumis melo (C. melo) has a long history as a lipid-lowering ethanopharmaceutical plant. In this study, compounds derived from C. melo were computationally evaluated as possible lead candidates. Various computational filtering methods were employed to assess the drug-like properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles of the compounds. The compounds were subsequently addressed to analysis of their interactions, molecular docking, and molecular dynamics simulation studies. When compared to the conventional therapeutic compounds, three compounds exhibited enhanced binding affinity and intra-molecular residue interactions, resulting in increased stability and specificity. Consequently, four potent inhibitors, namely PubChem CIDs 119205, 65373, 6184, and 332427, have been identified. These inhibitors exhibit promising potential as pharmacological targets for the advancement of novel ALR-2 inhibitors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Carbonic anhydrase CA-II enzyme is essential for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance due to its vital function within cellular processes. Herein, we screened 25 newly synthesized thiazole derivatives and assessed their inhibitory potential against the zinc-containing carbonic anhydrase CA-II enzyme. Intriguingly, derivatives of thiazole exhibited varying degrees of inhibitory action against CA-II. The distinctive attribute of these compounds is that they can attach to the CA-II binding site and block its action. Morpholine based thiazoles can be strategically modified to improve bovine CA-II inhibitor binding affinity, selectivity, and pharmacokinetics. Thiazole and morpholine moieties can boost inhibitory efficacy and selectivity over other calcium-binding proteins by interacting with target bovine CA-II binding sites. The derivatives 23-26 exhibited greater affinity when compared to the standard acetazolamide. Furthermore, kinetic study of the most potent compound 24 was performed, which exhibited concentration dependent inhibition with a K i value of 9.64 ± 0.007 μM. Molecular docking, MD simulation and QSAR analysis was also carried out to elucidate the interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, pharmacokinetic assessments showed that most of the compounds possess attributes conducive to potential drug development., Competing Interests: The authors have declared no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background/aims: The main focus of this investigation is to identify deleterious single nucleotide polymorphisms (SNPs) located in the BRCA2 gene through in silico approach, thereby,providing an understanding of potential consequences regarding the susceptibility to breast cancer., Methods: The GenomAD database was used to identify SNPs. To determine the potential adverse consequences, our study employed various prediction tools, including SIFT, PolyPhen, PredictSNP, SNAP2, PhD-SNP, and ClinVar. The pathogenicity associated with the deleterious snSNPs was evaluated bu MutPred and Fathmm. Additionally, I-Mutant and MuPro were used to assess the stability, followed by conservation and protein-protein interaction analysis using robust computational tools. The 3D structure of BRCA2 protein was generated by SwissModel, followed by validation using PROCHECK and Errat., Results: The GenomAD database was used to identify a total of 7, 921 SNPs, including 1940 missense SNPs. A set of 69 SNPs predicted by consensus to be damaging across all platforms was identified. Mutpred and Fathmm identified 48 and 38 SNPs, respectively to be associated with cancer. While I- Mutant and MuPro assays suggested 22 SNPs to decrease protein stability. Additionally, these 22 SNPs reside within highly conserved regions of the BRCA2 protein. Domain analysis, utilizing InterPro, pinpointed 18 deleterious mutations within crucial DNA binding domains and one in the BRC repeat region., Conclusion: This study establishes a foundation for future experimental validations and the creation of breast cancer-targeted treatment approaches., Competing Interests: The authors declared no competing interests and have nothing to disclose., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Heavy metals, specifically cadmium (Cd) and lead (Pb), contaminating water bodies of Madinah (Saudi Arabia), is a significant environmental concern that necessitates prompt action. Madinah is exposed to toxic metals from multiple sources, such as tobacco, fresh and canned foods, and industrial activities. This influx of toxic metals presents potential hazards to both human health and the surrounding environment. The aim of this study is to explore the viability of utilizing metallothionein from Pseudomonas putida ( P. putida ) as a method of bioremediation to mitigate the deleterious effects of pollution attributable to Pb and Cd. The use of various computational approaches, such as physicochemical assessments, structural modeling, molecular docking, and protein-protein interaction investigations, has enabled us to successfully identify the exceptional metal-binding properties that metallothionein displays in P. putida . The identification of specific amino acid residues, namely GLU30 and GLN21, is crucial in understanding their pivotal role in facilitating the coordination of lead and cadmium. In addition, post-translational modifications present opportunities for augmenting the capacity to bind metals, thereby creating possibilities for focused engineering. The intricate web of interactions among proteins serves to emphasize the protein's participation in essential cellular mechanisms, thereby emphasizing its potential contributions to detoxification pathways. The present study establishes a strong basis for forthcoming experimental inquiries, offering potential novel approaches in bioremediation to tackle the issue of heavy metal contamination. Metallothionein from P. putida presents a highly encouraging potential as a viable remedy for environmental remediation, as it is capable of proficiently alleviating the detrimental consequences related to heavy metal pollution.

Microorganisms are ubiquitously present in the environment and exert significant influence on numerous natural phenomena. The soil and groundwater systems, precipitation, and effluent outfalls from factories, refineries, and waste treatment facilities are all sources of heavy metal contamination. For example, Madinah, Saudi Arabia, has alarmingly high levels of lead and cadmium. The non-essential minerals cadmium (Cd) and lead (Pb) have been linked to damage to vital organs. Bioremediation is an essential component in the process of cleaning up polluted soil and water where biological agents such as bacteria are used to remove the contaminants. It is demonstrated that Pseudomonas aeruginosa ( P. aeruginosa) isolated from activated sludge was able to remove Cd and Pb from water. The protein sequence of metallothionein from P. aeruginosa was retrieved to explore it for physicoparameters, orthologs, domain, family, motifs, and conserved residues. The homology structure was generated, and models were validated. Docking of the best model with the heavy metals was carried out to inspect the intramolecular interactions. The target protein was found to belong to the "metallothionein_pro" family, containing six motifs, and showed a close orthologous relationship with other heavy metal-resistant bacteria. The best model was generated by Phyre2. In this study, three key residues of metallothionein were identified that participate in heavy metal (Pb and Cd) binding, viz., Ala33, Ser34, and Glu59. In addition, the study provides an essential basis to explore protein engineering for the optimum use of metallothionein protein to reduce/remove heavy metals from the environment.

Monoamine oxidase and cholinesterase enzymes are important targets for the treatment of several neurological diseases especially depression, Parkinson disease and Alzheimer's. Here, we report the synthesis and testing of new 1,3,4-oxadiazole derivatives as novel inhibitors of monoamine oxidase enzymes (MAO-A and MAO-B) and cholinesterase enzymes (acetyl and butyryl cholinesterase (AChE, BChE). Compounds 4c, 4d, 4e, 4g, 4j, 4k, 4m, 4n displayed promising inhibitory effects on MAO-A (IC 50 : 0.11-3.46 μM), MAO-B (IC 50 : 0.80-3.08 μM) and AChE (IC 50 : 0.83-2.67 μM). Interestingly, compounds 4d, 4e and 4g are multitargeting MAO-A/B and AChE inhibitors. Also, Compound 4m displayed promising MAO-A inhibition with IC 50 of 0.11 μM and high selectivity (∼25-fold) over MAO-B and AChE enzymes. These newly synthesized analogues represent promising hits for the development of promising lead compounds for neurological disease treatment., Competing Interests: The authors declare that they have no significant conflict of interest., (This journal is © The Royal Society of Chemistry.)

The development of an effective and selective chemosensor for CN - ions has become the need of the hour due to their hazardous impact on the environment and humans. Herein, we report the synthesis of two novel chemosensors, IF-1 and IF-2 based on 3-hydroxy-2-naphthohydrazide and aldehyde derivatives that have shown selective sensing of CN - ions. IF-2 exhibited exclusive binding with CN - ions that is further confirmed by the binding constant value of 4.77 × 10 4 M -1 with a low detection limit (8.2 μM). The chemosensory potential is attributed to deprotonation of the labile Schiff base center by CN - ions that results in a color change from colorless to yellow as visible by the naked eye. Accompanying this, a DFT study was also performed in order to find the interaction between the sensor (IF-1) and its ions (F - ). A notable charge transfer from 3-hydroxy-2-naphthamide to 2,4-di- tert -butyl-6-methylphenol, was indicated by the FMO analysis. The QTAIM analysis revealed that in the complex compound, the strongest pure hydrogen-hydrogen bonding was observed between H53 and H58, indicated by a ρ value of +0.017807. Due to its selective response, IF-2 can be successfully used for making test strips for the detection of CN - ions., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (This journal is © The Royal Society of Chemistry.)

Diabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the discovery of potent natural inhibitors is desired. In response, a pharmacophore model based on the properties of eplarestat was generated. The specified pharmacophore model searched the NuBBE DB database of natural compounds for prospective lead candidates. To assess the drug-likeness and ADMET profile of the compounds, a series of in silico filtering procedures were applied. The compounds were then put through molecular docking and interaction analysis. In comparison to the reference drug, four compounds showed increased binding affinity and demonstrated critical residue interactions with greater stability and specificity. As a result, we have identified four potent inhibitors: ZINC000002895847, ZINC000002566593, ZINC000012447255, and ZINC000065074786, that could be used as pharmacological niches to develop novel ALR-2 inhibitors.

Diabetes is a complicated multifactorial disorder in which the patient generally observes polyphagia, polydipsia, and polyuria due to uncontrolled growth in blood sugar levels. For its management, the pharmaceutical industry is working day and night to find a better drug with no or least toxicity. That's why nowadays a more focused branch is to use herbal phytoconstituents for its prevention. Shikonin is a naphthoquinone natural dye that is isolated from the plants of the Boraginaceae family and has proven its role as an anti-cancer, anti-inflammatory, and anti-gonadotrophic agent. In our previous study, we have published its anti-diabetic action by inhibiting the enzyme protein tyrosine phosphatase 1B. In this study, we were more focused on finding out the role of Shikonin and its pharmacophores by inhibiting the action of aldose reductase (AR) enzyme. The study was conducted using pharmacophore modeling, molecular docking, and molecular dynamics simulation studies. The absorption, distribution, metabolism, excretion (ADME), and toxicity profile were also evaluated in this study. Along with all the computational biology parameters we also focused on the in vitro activity and kinetic study of inhibitory activity of Shikonin against aldose reductase., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Panicle blast is the most severe type of rice blast disease. Screening of rice genotypes for panicle blast resistance at the field level requires an efficient and robust method of inoculation. Here, we standardized a method that can be utilized for both small- and large-scale screening and assessment of panicle blast infection and disease reaction. The method involves inoculation of Magnaporthe oryzae spore culture in the neck of the rice panicle using a syringe and covering the inoculation site with wet cotton wrapped with aluminum foil to provide the required humidity for spore germination. The method was standardized using panicle blast-resistant cv. Tetep and susceptible cv. HP2216 inoculated with Mo-ni-025 isolate of M. oryzae . The method was evaluated at phenotypic as well as molecular level by expression analysis of disease responsive pathogenesis-related (PR) genes. We found this method simple, robust, reliable, and highly efficient for screening of large germplasm sets of rice for panicle blast. This was validated by screening the wild rice germplasm for panicle blast response in the field using three M. oryzae strains and subsequently with the most virulent strain in 45 EMS-induced mutants of Nagina 22 shortlisted based on field screening in a blast hotspot region. We identified five novel blast disease-resistant wild rice genotypes and 15 Nagina 22 mutants that can be used in breeding programmes., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest in the publication., (© King Abdulaziz City for Science and Technology 2022.)

The use of pharmaceuticals to treat Major Depressive Disorder (MDD) has several drawbacks, including severe side effects. Natural compounds with great efficacy and few side effects are in high demand due to the global rise in MDD and ineffective treatment. Yohimbine, a natural compound, has been used to treat various ailments, including neurological conditions, since ancient times. Serotonergic neurotransmission plays a crucial role in the pathogenesis of depression; thus, serotonergic receptor agonist/antagonistic drugs are promising anti-depressants. Yohimbine was investigated in this study to determine its antidepressant activity using molecular docking and pharmacokinetic analyses. Additionally, the in silico mutational study was carried out to understand the increase in therapeutic efficiency using site-directed mutagenesis. Conformational changes and fluctuations occurring during wild type and mutant serotonergic receptor, 5-hydroxytryptamine receptors 1A (5HT1A) and yohimbine were assessed by molecular dynamics MD simulation studies. Yohimbine was found to satisfy all the parameters for drug-likeness and pharmacokinetics analysis. It was found to possess a good dock score and hydrogen-bond interactions with wild type 5HT1A structure. Our findings elaborate the substantial efficacy of yohimbine against MDD; however, further bench work studies may be carried out to prove the same.

Considering the current dramatic and fatal situation due to the high spreading of SARS-CoV-2 infection, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of Coronavirus disease (COVID 19) by re-evaluating and repurposing of known drugs. For this, tomatidine and patchouli alcohol have been selected as potential drugs for combating the virus. The hit compounds were subsequently docked into the active site and molecular docking analyses revealed that both drugs can bind the active site of SARS-CoV-2 3CLpro, PLpro, NSP15, COX-2 and PLA2 targets with a number of important binding interactions. To further validate the interactions of promising compound tomatidine, Molecular dynamics study of 100 ns was carried out towards 3CLpro, NSP15 and COX-2. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post dynamic MM-GBSA analysis of molecular dynamics data showed promising mean binding free energy 47.4633 ± 9.28, 51.8064 ± 8.91 and 54.8918 ± 7.55 kcal/mol, respectively. Likewise, in silico ADMET studies of the selected ligands showed excellent pharmacokinetic properties with good absorption, bioavailability and devoid of toxicity. Therefore, patchouli alcohol and especially, tomatidine may provide prospect treatment options against SARS-CoV-2 infection by potentially inhibiting virus duplication though more research is guaranteed and secured.

Minichromosome maintenance complex component 7 (MCM7) is involved in replicative licensing and the synthesis of DNA, and its overexpression is a fascinating biomarker for various cancer types. There is currently no effective agent that can prevent the development of cancer caused by the MCM7 protein. However, on the molecular level, inhibiting MCM7 lowers cancer-related cellular growth. With this purpose, this study screened 452 biogenic compounds extracted from the UEFS Natural Products dataset against MCM protein by using the in silico art of technique. The hit compounds UEFS99, UEFS137, and UEFS428 showed good binding with the MCM7 protein with binding energy values of -9.95, -8.92, and -8.71 kcal/mol, which was comparatively higher than that of the control compound ciprofloxacin (-6.50). The hit (UEFS99) with the minimum binding energy was picked for molecular dynamics (MD) simulation investigation, and it demonstrated stability at 30 ns. Computational prediction of physicochemical property evaluation revealed that these hits are non-toxic and have good drug-likeness features. It is suggested that hit compounds UEFS99, UEFS137, and UEFS428 pave the way for further bench work validation in novel inhibitor development against MCM7 to fight the cancers.

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin's in silico interaction with protein tyrosine phosphate 1B, as well as it's in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule's module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.

The coronaviruses have caused severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS), and the more recent coronavirus pneumonia (COVID-19). The global COVID-19 pandemic requires urgent action to develop anti-virals, new therapeutics, and vaccines. In this review, we discuss potential therapeutics including human recombinant ACE2 soluble, inflammatory cytokine inhibitors, and direct anti-viral agents such as remdesivir and favipiravir, to limit their fatality. We also discuss the structure of the SARS-CoV-2, which is crucial to the timely development of therapeutics, and previous attempts to generate vaccines against SARS-CoV and MERS-CoV. Finally, we provide an overview of the role of nanotechnology in the development of therapeutics as well as in the diagnosis of the infection. This information is key for computational modeling and nanomedicine-based new therapeutics by counteracting the variable proteins in the virus. Further, we also try to effectively share the latest information about many different aspects of COVID-19 vaccine developments and possible management to further scientific endeavors., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 The Authors. VIEW published by Shanghai Fuji Technology Consulting Co., Ltd, authorized by Professional Community of Experimental Medicine, National Association of Health Industry and Enterprise Management (PCEM) and John Wiley & Sons Australia, Ltd.)

Gamma irradiation has been reported to modulate the biochemical and molecular parameters associated with the tolerance of plant species under biotic/ abiotic stress. Wheat is highly sensitive to heat stress (HS), as evident from the decrease in the quantity and quality of the total grains. Here, we studied the effect of pre-treatment of wheat dry seeds with different doses of gamma irradiation (0.20, 0.25 and 0.30 kGy) on tolerance level and quality of developing wheat endospermic tissue under HS (38 °C, 1 h; continuously for three days). Expression analysis of genes associated with defence and starch metabolism in developing grains showed maximum transcripts of HSP17 (in response to 0.25 kGy + HS) and AGPase (under 0.30 kGy), as compared to control. Gamma irradiation was observed to balance the accumulation of H 2 O 2 by enhancing the activities of SOD and GPx in both the cvs. under HS. Gamma irradiation was observed to stabilize the synthesis of starch and amylose by regulating the activities of AGPase, SSS and α-amylase under HS. The appearance of isoforms of gliadins (α, β, γ, ω) were observed more in gamma irradiated seeds (0.20 kGy), as compared to control. Gamma irradiation (0.25 kGy in HD3118 & 0.20 kGy in HD3086) was observed to have positive effect on the width, length and test seed weight of the grains under HS. The information generated in present investigation provides easy, cheap and user-friendly technology to mitigate the effect of terminal HS on the grain-development process of wheat along with development of robust seeds with high nutrient density., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Terminal heat stress has detrimental effect on the growth and yield of wheat. Very limited information is available on heat stress-associated active proteins (SAAPs) in wheat. Here, we have identified 159 protein groups with 4271 SAAPs in control (22 ± 3 °C) and HS-treated (38 °C, 2 h) wheat cvs. HD2985 and HD2329 using iTRAQ. We identified 3600 proteins to be upregulated and 5825 proteins to be downregulated in both the wheat cvs. under HS. We observed 60.3% of the common SAAPs showing upregulation in HD2985 (thermotolerant) and downregulation in HD2329 (thermosusceptible) under HS. GO analysis showed proton transport (molecular), photosynthesis (biological), and ATP binding (cellular) to be most altered under HS. Most of the SAAPs identified were observed to be chloroplast localized and involved in photosynthesis. Carboxylase enzyme was observed most abundant active enzymes in wheat under HS. An increase in the degradative isoenzymes (α/β-amylases) was observed, as compared to biosynthesis enzymes (ADP-glucophosphorylase, soluble starch synthase, etc.) under HS. Transcript profiling showed very high relative fold expression of HSP17, CDPK, Cu/Zn SOD, whereas downregulation of AGPase, SSS under HS. The identified SAAPs can be used for targeted protein-based precision wheat-breeding program for the development of 'climate-smart' wheat.

The objective of this study was to compare graft uptake and hearing improvement in active and inactive mucosal chronic otitis media patients after endoscopic myringoplasty. This is prospective study conducted at a government medical college and hospital from February 2014 to August 2015. A total of 40 active (wet) ears with mucoid discharge and 40 inactive (dry) ears (at least 6 weeks dry before surgery) with mucosal chronic otitis media were operated on by endoscopic myringoplasty by transcanal approach. Graft uptake and hearing gain rates 3 months after surgery were compared for both groups. Endoscopic myringoplasty using temporal fascia graft via transcanal approach was used. The graft take rate was 77.5% for the active ear group and 85% for the inactive ear group. The hearing gain rate was 82.5% for the inactive ear group and 72.5% for the active ear group. Differences were found to be statistically insignificant for both graft uptake and hearing gain. The success of endoscopic myringoplasty is not adversely affected by the presence of mucoid ear discharge at the time of surgery, and outcomes are comparable to those of the operation done for inactive ear.

The scope of the Human Disease Insight (HDI) database is not limited to researchers or physicians as it also provides basic information to non-professionals and creates disease awareness, thereby reducing the chances of patient suffering due to ignorance. HDI is a knowledge-based resource providing information on human diseases to both scientists and the general public. Here, our mission is to provide a comprehensive human disease database containing most of the available useful information, with extensive cross-referencing. HDI is a knowledge management system that acts as a central hub to access information about human diseases and associated drugs and genes. In addition, HDI contains well-classified bioinformatics tools with helpful descriptions. These integrated bioinformatics tools enable researchers to annotate disease-specific genes and perform protein analysis, search for biomarkers and identify potential vaccine candidates. Eventually, these tools will facilitate the analysis of disease-associated data. The HDI provides two types of search capabilities and includes provisions for downloading, uploading and searching disease/gene/drug-related information. The logistical design of the HDI allows for regular updating. The database is designed to work best with Mozilla Firefox and Google Chrome and is freely accessible at http://humandiseaseinsight.com., (Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

An extensive analysis of C. dubliniensis proteomics data showed that ~22% protein are conserved hypothetical proteins (HPs) whose function is still not determined precisely. Analysis of gene sequence of HPs provides a platform to establish sequence-function relationships to a more profound understanding of the molecular machinery of organisms at systems level. Here we have combined the latest versions of bioinformatics tools including, protein family, motifs, intrinsic features from the amino acid sequence, sequence-function relationship, pathway analysis, etc. to assign a precise function to HPs for which no any experimental information is available. Our results show that 27 HPs have well defined functions and we categorized them as enzyme, nucleic acid binding, transport protein, etc. Five HPs showed adhesin character that is likely to be essential for the survival of yeast and pathogenesis. We also addressed issues related to the sub-cellular localization and signal peptide identification which provides an idea about its colocalization and function. The outcome of the present study may facilitate better understanding of mechanism of virulence, drug resistance, pathogenesis, adaptability to host, tolerance for host immune response, and drug discovery for treatment of C. dubliniensis infections., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Protein-Protein interactions (PPIs) are vital to most biological processes thus the identification of PPIs is of primary importance. Here, we endeavor to identify the downstream interacting partners of (BjMPK3P) in Brassica juncea using the docking approach. Out of 63 and 37 members of BrWRKY and BnWRKY transcription factors, 50 and 29 members are showing interactions with BjMPK3P respectively while the rest are showing non-interaction. Twenty two WRKY members are common to both the species. Using minimal sequence motif search as well as through docking approach several novel WRKY interacting proteins were also reported in the present study which need to be confirmed by in vitro kinase assay. Together, the results obtained essentially enhance our knowledge of the MAPK interacting protein network and provide a valuable research resource for developing a nearly important link between pathogen-activated MAPK signaling pathways and downstream transcriptional programming.