•Mycoremediation of polycyclic aromatic hydrocarbons, challenges, and strategies to overcome.•Role of the fungi in eradicating heavy metal contamination from the polluted sites.•Mycoremediation of ...agricultural wastes including pesticides, herbicides, and cyanotoxins.•Pharmaceutical wastes and strategies for its remediation using white-rot and ligninolytic fungus.
The ever-increasing population, rapid rate of urbanization, and industrialization are exacerbating the pollution-related problems. Soil and water pollution affect human health and the ecosystem. Thus, it is crucial to develop strategies to combat this ever-growing problem. Mycoremediation, employing fungi or its derivatives for remediation of environmental pollutants, is a comparatively cost-effective, eco-friendly, and effective method. It has advantages over other conventional and bioremediation methods. In this review, we have elucidated the harmful effects of common pollutants on public health and the environment. The role of several fungi in degrading these pollutants such as heavy metals, agricultural, pharmaceutical wastes, including polycyclic aromatic hydrocarbons, is enumerated. Future strategies to improve the rate and efficiency of mycoremediation are suggested. The manuscript describes the strategies which can be used as a future framework to address the global problem of pollution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Candida auris is a rapidly emerging human pathogenic fungus with a high mortality rate. Recent report suggests that the new clinical isolates are showing resistance to the major classes of antifungal ...drugs. Due to the emergence of drug resistance, it becomes imperative to seek novel therapies for the treatment of C. auris. The potent vaccine could be one of the promising strategies for recalcitrant and multidrug-resistant pathogens. Using in silico approach we designed a novel multivalent vaccine against C. auris. We have selected the agglutinin-like sequence-3 (Als3) an adhesion protein, involved in virulence. The Als3p protein of C. auris was targeted to predict T cell and B cell epitopes. Epitopes which were found to be non-toxic, non-allergenic, highly conserved, and antigenic and could induce interferon-γ synthesis were selected for vaccine design. The selected epitopes were linked with suitable adjuvants to construct the final vaccine. The vaccine construct was predicted to be stable, soluble, antigenic, non-allergic with desirable physicochemical properties. We also constructed the 3D model of the vaccine and validated it with the Ramachandran plot. The ability of the vaccine construct to interact with Toll-like receptor (TLR) and major histocompatibility complex (MHC) was determined by molecular docking experiments. The binding energy of the vaccine construct with the TLR and MHC were found to be stable as predicted by molecular dynamics simulation. Further, in-silico cloning analysis showed that the vaccine construct can be successfully cloned and expressed in E. coli. Based on the results, we surmise that our candidate vaccine can be used as an alternative therapy for the treatment of C. auris. However, the efficacy and the safety of the vaccine model need to be determined by performing in vivo studies.
•Candida auris is a rapidly emerging human pathogenic fungus with high mortality rate.•A multi-epitope subunit-based vaccine against C. auris is designed using in-silico tools.•The vaccine was constructed using 8 highly antigenic epitopes, PADRE sequence, and adjuvant linked together by GGS linker.•The results show that the vaccine construct is highly antigenic but at the same time non-toxic, and non-allergenic.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Protein kinase R (PKR) functions in a plethora of cellular processes, including viral and cellular stress responses, by phosphorylating the translation initiation factor eIF2α. The minimum ...requirements for PKR function are homodimerization of its kinase and RNA-binding domains, and autophosphorylation at the residue Thr-446 in a flexible loop called the activation loop. We investigated the interdependence between dimerization and Thr-446 autophosphorylation using the yeast Saccharomyces cerevisiae model system. We showed that an engineered PKR that bypassed the need for Thr-446 autophosphorylation (PKRT446∼P-bypass mutant) could function without a key residue (Asp-266 or Tyr-323) that is essential for PKR dimerization, suggesting that dimerization precedes and stimulates activation loop autophosphorylation. We also showed that the PKRT446∼P-bypass mutant was able to phosphorylate eIF2α even without its RNA-binding domains. These two significant findings reveal that PKR dimerization and activation loop autophosphorylation are mutually exclusive yet interdependent processes. Also, we provide evidence that Thr-446 autophosphorylation during PKR activation occurs in a cis mechanism following dimerization.
PKR regulates many biological processes including stress response.
An activation-loop-phosphorylation bypass mutant of PKR functions without a key dimer-interface residue. The PKR kinase domain together with a kinase-dead partner, but not alone, activates the catalytic function.
Activation loop phosphorylation occurs in cis following dimerization.
PKR autophosphorylates in the activation loop in cis to initiate the antiviral signaling cascade.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A new virus termed SARS-COV-2 (causing COVID-19 disease) can exhibit a progressive, fatal impact on individuals. The World Health Organization (WHO) has declared the spread of the virus to be a ...global pandemic. Currently, there are over 1 million cases and over 100,000 confirmed deaths due to the virus. Hence, prophylactic and therapeutic strategies are promptly needed. In this study we report an epitope, ITLCFTLKR, which is biochemically fit to HLA allelic proteins. We propose that this could be used as a potential vaccine candidate against SARS-COV-2. A selected putative epitope and HLA-allelic complexes show not only better binding scores, but also RMSD values in the range of 0–1 Å. This epitope was found to have a 99.8% structural favorability as per Ramachandran-plot analysis. Similarly, a suitable range of IC50 values and population coverage was obtained to represent greater validation of T-cell epitope analysis. Stability analysis using MDWeb and half-life analysis using the ProtParam tool has confirmed that this epitope is well-selected. This new methodology of epitope-based vaccine prediction is fundamental and fast in application, ad can be economically beneficial and viable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Candida tropicalis
causes tropical invasive fungal infections, with a high mortality. This fungus has been found to be resistant to antifungal classes such as azoles, echinocandins, and ...polyenes in several studies. As a result, it is vital to identify novel approaches to prevent and treat
C. tropicalis
infections. In this study, an in silico technique was utilized to deduce and evaluate a powerful multivalent epitope-based vaccine against
C. tropicalis
, which targets the secreted aspartic protease 2 (SAP2) protein. This protein is implicated in virulence and host invasion.
Results
By focusing on the Sap2 protein, 11 highly antigenic, non-allergic, non-toxic, and conserved epitopes were identified. These were subsequently paired with RS09 and flagellin adjuvants, as well as a pan HLA DR-binding epitope (PADRE) sequence to create a vaccine candidate that elicited both cell-mediated and humoral immune responses. It was projected that the vaccine design would be soluble, stable, antigenic, and non-allergic. Ramachandran plot analysis was applied to validate the vaccine construct’s 3-dimensional model. The vaccine construct was tested (at 100 ns) using molecular docking and molecular dynamics simulations, which demonstrated that it can stably connect with MHC-I and Toll-like receptor molecules. Based on in silico studies, we have shown that the vaccine construct can be expressed in
E. coli
. We surmise that the vaccine design is unrelated to any human proteins, indicating that it is safe to use.
Conclusions
The vaccine design looks to be an effective option for preventing
C. tropicalis
infections, based on the outcomes of the studies. A fungal vaccine can be proposed as prophylactic medicine and could provide initial protection as sometimes diagnosis of infection could be challenging. However, more in vitro and in vivo research is needed to prove the efficacy and safety of the proposed vaccine design.
Neural necrosis virus (NNV) of family Nodaviridae affect wide range of fish species with viral encephalopathy and retinopathy causing mass mortality up to 100%. Currently there is no effective ...treatment and depopulation is only suggested recommendation. New avenues and approach are required to control this harmful malady. In this study we developed an epitope-based vaccine (EBV), against NNV using computation approach. We have selected two conserved proteins RNA-dependent RNA polymerase (RdRP) and capsid proteins. Based on more than ~ 1000 epitopes we selected six antigenic epitopes. These were conjugated to adjuvant and linker peptides to generate a full-length vaccine candidate. Biochemical structural properties were analyzed by Phyre2 server. ProtParam, Molprobity. Ramachandran plot results indicate that 98.7% residues are in a favorable region and 93.4% residues in the favored region. The engineered EBV binds to toll like receptor-5 (TLR5) an important elicitor of immune response. Further molecular docking by PatchDock server reveals the atomic contact energy (i.e. − 267.08) for the best docked model of EBV and TLR5 receptor. The molecular simulation results suggest a stable interaction; the RMSD and RMSF values are 1–4 Ǻ and 1–12Ǻ, respectively. Further we have suggested the best possible codon optimized sequence for its cloning and subsequent purification of the protein. Overall, this is a first report to suggest an in-silico method for generation of an EBV candidate against NNV. We surmise that the method and approach suggested could be used as a promising cure for NNVs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Renewable energy has become the most prominent source of energy to reduce carbon emissions around the globe. Undoubtedly, hydro energy is very much clean energy among other sources. In Bangladesh, ...hydro energy is available only in a specific southern area contributing several hundred megawatts to the national grid. This paper devotes to assessing the capacity and practicability of a hydropower plant to boost the power output by implementing the combined cycle hydropower system. The proposed method has been developed by 1) studying the existing plant based on surveyed data, 2) selecting the site for installing the hydrokinetic turbine, 3) designing with consideration of numerous constraints of inter dependability, and 4) creating a prototype model to ensure the practicability. Preliminary results show that a significant amount of additional electric energy can be generated from the plant with higher efficiency.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite an increase in life expectancy over the past 20 years, the number of novel, multi-drug resistant microorganisms has also risen dramatically. To reduce the risk of reemerging infections, and ...limit the spread of multidrug resistant microorganisms, it is urgently necessary to develop safe and effective therapeutic countermeasures. New antimicrobial chemicals are mostly produced with the help of microorganisms, and the bulk of medications now on the market are of this type. The use of high therapeutic screening and recent developments in analytical instrumentation has allowed the researchers to identify novel antimicrobial compounds from bacteria, fungi, plants, mushrooms, algae, and other sources more quickly. The second volume of Frontiers in Antimicrobial Agents highlights the ongoing requirement for researching and creating novel antimicrobial medications. Current Trends in the Identification and Development of Antimicrobial Agents aims to bring together the expertise of notable academics to examine all facets of antimicrobial research while keeping recent advancements in perspective. Antibiotic discovery, sources of novel antimicrobial chemicals, developing and reemerging microbial infections, various elements of drug resistance, and the need for antimicrobial medications in the future are all covered in this book. It is a timely reference for anyone involved in the discovery and development of new drugs, including microbiologists, biotechnologists, pharmacologists, doctors, and researchers.
The Hac1 transcription factor in yeast up-regulates a collection of genes that control protein homeostasis. Base-pairing interactions between sequences in the intron and the 5′-untranslated region ...(5′ UTR) of the HAC1 mRNA represses Hac1 protein production under basal conditions, whereas cytoplasmic splicing of the intron by the Ire1 kinase-endonuclease, activated under endoplasmic reticulum stress conditions, relieves the inhibition and enables Hac1 synthesis. Using a random mutational screen as well as site-directed mutagenesis, we identify point mutations within the 5′ UTR-intron interaction site that derepress translation of the unspliced HAC1 mRNA. We also show that insertion of an in-frame AUG start codon upstream of the interaction site releases the translational block, demonstrating that an elongating ribosome can disrupt the interaction. Moreover, overexpression of translation initiation factor eIF4A, a helicase, enhances production of Hac1 from an mRNA containing an upstream AUG start codon at the beginning of the base-paired region. These results suggest that the major block of translation occurs at the initiation stage. Supporting this interpretation, the point mutations that enhanced Hac1 production resulted in an increased percentage of the HAC1 mRNA associating with polysomes versus free ribosomal subunits. Thus, our results provide evidence that the 5′ UTR-intron interaction represses translation initiation on the unspliced HAC1 mRNA.
Background: Hac1 protein, encoded by a cytoplasmically spliced mRNA, activates the unfolded protein response to maintain cellular protein homeostasis and alleviate endoplasmic reticulum stress.
Results: Under non-stress conditions, translation initiation on the HAC1 mRNA is repressed.
Conclusion: Base-pairing interaction between the 5′ leader and intron represses translation initiation on the HAC1 mRNA.
Significance: A unique mechanism of intron-mediated inhibition of ribosomal scanning.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Candida auris is a rapidly emerging global public health concern. The increasing mortality in immunocompromised patients is mostly attributed to the rise of drug-resistant clinical isolates. Low ...bioavailability and toxicity of the existing antifungals further exacerbate the condition. Unfolded protein response (UPR) has been linked to fungal pathogenesis in previous studies. In this study the two hallmark proteins of the UPR pathway, Hac1p and Ire1p, were targeted to identify novel antifungals. Different phytochemicals showing various therapeutic potential were selected. Using various bioinformatics tools, the molecular property, bioactivity, toxicity, drug-likeness of these compounds were determined. The compounds showing the best properties were analyzed for their ability to interact with UPR proteins by molecular docking study. Finally, the molecular dynamics simulation analysis was performed to determine the stability of the interactions between the phytochemicals and the target protein. Flinderole-B, Drummondin-E, Betulinic acid, Ursolic acid, Oleanolic acid, Stigmasterol showed good drug-likeness scores. They were also found to be non-carcinogenic, and non-toxic; and followed Lipinski’s rule of five. Based on the simulation analysis Betulinic acid showed the best potential to target Hac1p while Drummondin-E showed the best potential to target Ire1p. Betulinic acid and Drummondin E could be potential inhibitors of the UPR pathway in C. auris. However, further in vitro and in vivo studies are needed to corroborate their antifungal potential.
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