Biofouling effects on the performance of microbial fuel cells and recent advances in biotechnological and chemical strategies for mitigation

The occurrence of biofouling in MFC can cause severe problems such as hindering proton transfer and increasing the ohmic and charge transfer resistance of cathodes, which results in a rapid decline in performance of MFC. This is one of the main reasons why scaling-up of MFCs has not yet been successfully accomplished. The present review article is a wide-ranging attempt to provide insights to the biofouling mechanisms on surfaces of MFC, mainly on proton exchange membranes and cathodes, and their effects on performance of MFC based on theoretical and practical evidence. Various biofouling mitigation techniques for membranes are discussed, including preparation of antifouling composite membranes, modification of the physical and chemical properties of existing membranes, and coating with antifouling agents. For cathodes of MFC, use of Ag nanoparticles, Ag-based composite nanoparticles, and antifouling chemicals is outlined in considerable detail. Finally, prospective techniques for mitigation of biofouling are discussed, which have not been given much previous attention in the field of MFC research. This article will help to enhance understanding of the severity of biofouling issues in MFCs and provides up-to-date solutions. It will be beneficial for scientific communities for further strengthening MFC research and will also help in progressing this cutting-edge technology to scale-up, using the most efficient methods as described here.     

Molecular dynamics and combined docking studies for the identification of Zaire ebola virus inhibitors

Ebola virus (EBOV) is a lethal human pathogen with a risk of global spread of its zoonotic infections, and Ebolavirus Zaire specifically has the highest fatality rate amongst other species. There is a need for continuous effort towards having therapies, as a single licensed treatment to neutralize the EBOV is yet to come into reality. This present study virtually screened the MCULE database containing almost 36 million compounds against the structure of a Zaire Ebola viral protein (VP) 35 and a consensus scoring of both MCULE and CLCDDW docking programs remarked five compounds as potential hits. These compounds, with binding energies ranging from –7.9 to –8.9?kcal/mol, were assessed for predictions of their physicochemical and bioactivity properties, as well as absorption, distribution, metabolism, excretion, and toxicity (ADMET) criteria. The results of the 50?ns molecular dynamics simulations showed the presence of dynamic stability between ligand and protein complexes, and the structures remained significantly unchanged at the ligand-binding site throughout the simulation period. Both docking analysis and molecular dynamics simulation studies suggested strong binding affinity towards the receptor cavity and these selected compounds as potential inhibitors against the Zaire Ebola VP 35. With respect to inhibition constant values, bioavailability radar and other physicochemical properties, compound A (MCULE-1018045960-0-1) appeared to be the most promising hit compound. However, the ligand efficiency and ligand efficiency scale need improvement during optimization, and also validation via in vitro and in vivo studies are necessary to finally make a lead compound in treating Ebola virus diseases.

Communicated by Ramaswamy H. Sarma     

Effects of Pro1266Leu mutation on structure and function of glycoprotein Ib binding domain of von Willebrand factor

Glycoprotein Ibα (GpIbα) binding ability of A1 domain of von Willebrand factor (vWF) facilitates platelet adhesion that plays a crucial role in maintaining hemostasis and thrombosis at the site of vascular damage. There are both “loss as well as gain of function” mutations observed in this domain. Naturally occurring “gain of function” mutations leave self-activating impacts on the A1 domain which turns the normal binding to characteristic constitutive binding with GPIbα. These “gain of function” mutations are associated with the von Willebrand disease type 2B. In recent years, studies focused on understanding the mechanism and conformational patterns attached to these phenomena have been conducted, but the conformational pathways leading to such binding patterns are poorly understood as of now. To obtain a microscopic picture of such events for the better understanding of pathways, we used molecular dynamics (MD) simulations along with principal component analysis and normal mode analysis to study the effects of Pro1266Leu (Pro503Leu in structural context) mutation on the structure and function of A1 domain of vWF. MD simulations have provided atomic-level details of intermolecular motions as a function of time to understand the dynamic behavior of A1 domain of vWF. Comparative analysis of the trajectories obtained from MD simulations of both the wild type and Pro503Leu mutant suggesting appreciable conformational changes in the structure of mutant which might provide a basis for assuming the “gain of function” effects of these mutations on the A1 domain of vWF, resulting in the constitutive binding with GpIbα.     

Investigation of deleterious effects of nsSNPs in the POT1 gene: a structural genomics-based approach to understand the mechanism of cancer development

Protection of telomere 1 (POT1) is one of the key components of shelterin complex, implicated in maintaining the telomere homeostasis, and thus stability of the eukaryotic genome. A large number of non-synonymous single nucleotide polymorphisms (nsSNPs) in the POT1 gene have been reported to cause varieties of human diseases, including cancer. In recent years, a number of mutations in POT1 has been markedly increased, and interpreting the effect of these large numbers of mutations to understand the mechanism of associated diseases seems impossible using experimental approaches. Herein, we employ varieties of computational methods such as PROVEAN, PolyPhen-2, SIFT, PoPMuSiC, SDM2, STRUM, and MAESTRO to identify the effects of 387 nsSNPs on the structure and function of POT1 protein. We have identified about 183 nsSNPs as deleterious and termed them as “high-confidence nsSNPs.” Distribution of these high-confidence nsSNPs demonstrates that the mutation in oligonucleotide binding domain 1 is highly deleterious (one in every three nsSNPs), and high-confidence nsSNPs show a strong correlation with residue conservation. The structure analysis provides a detailed insights into the structural changes occurred in consequence of conserved mutations which lead to the cancer progression. This study, for the first time, offers a newer prospective on the role of POT1 mutations on the structure, function, and their relation to associated diseases.     

Structure-guided affinity maturation of a single-chain variable fragment antibody against the Fu-bc epitope of the dengue virus envelope protein

Dengue is one of the most dominant arthropod-borne viral diseases, infecting at least 390 million people every year throughout the world. Despite this, there is no effective treatment against dengue, and the only available vaccine has already been withdrawn owing to the significant adverse effects. Therefore, passive immunotherapy using monoclonal antibodies is now being sought as a therapeutic option. To date, many dengue monoclonal antibodies have been identified, most of which are serotype-specific, and only a few of which are cross-reactive. Furthermore, antibodies that cross-react within serotypes are weakly neutralizing and frequently induce antibody-dependent enhancement, which promotes viral entry and replication. Therefore, broadly neutralizing antibodies with no risk of antibody-dependent enhancement are required for the treatment of dengue. Here, we developed a single-chain variable fragment (scFv) antibody from an anti-fusion loop E53 antibody (PDB: 2IGF). We introduced previously predicted favorable complementarity-determining region (CDR) mutations into the gene encoding the scFv antibody for affinity maturation, and the resultant variants were tested in vitro against the highly conserved fusion and bc epitope of the dengue virus envelope protein. We show some of these scFv variants with two to three substitution mutations in three different CDRs possess affinity constants (K_D) ranging from 20 to 200 nM. The scFv-mutant15, containing D31L, Y105W, and S227W substitutions, showed the lowest affinity constant, (K_D = 24 ± 7 nM), approximately 100-fold lower than its parental construct. We propose that the scFv-derivative antibody may be a good candidate for the development of an effective and safe immunotherapy.     

Elucidating Drug-Like Compounds and Potential Mechanisms of Corn Silk (Stigma Maydis) against Obesity: A Network Pharmacology Study

Corn silk (Stigma Maydis) has been utilized as an important herb against obesity by Chinese, Korean, and Native Americans, but its phytochemicals and mechanisms(s) against obesity have not been deciphered completely. This study aimed to identify promising bioactive constituents and mechanism of action(s) of corn silk (CS) against obesity via network pharmacology. The compounds from CS were identified using Gas Chromatography Mass Spectrometry (GC-MS) and were confirmed ultimately by Lipinski’s rule via SwissADME. The relationships of the compound-targets or obesity-related targets were confirmed by public bioinformatics. The signaling pathways related to obesity, protein-protein interaction (PPI), and signaling pathways-targets-bioactives (STB) were constructed, visualized, and analyzed by RPackage. Lastly, Molecular Docking Test (MDT) was performed to validate affinity between ligand(s) and protein(s) on key signaling pathway(s). We identified a total of 36 compounds from CS via GC-MS, all accepted by Lipinski’s rule. The number of 36 compounds linked to 154 targets, 85 among 154 targets related directly to obesity-targets (3028 targets). Of the final 85 targets, we showed that the PPI network (79 edges, 357 edges), 12 signaling pathways on a bubble chart, and STB network (67 edges, 239 edges) are considered as therapeutic components. The MDT confirmed that two key activators (β-Amyrone, β-Stigmasterol) bound most stably to PPARA, PPARD, PPARG, FABP3, FABP4, and NR1H3 on the PPAR signaling pathway, also, three key inhibitors (Neotocopherol, Xanthosine, and β-Amyrone) bound most tightly to AKT1, IL6, FGF2, and PHLPP1 on the PI3K-Akt signaling pathway. Overall, we provided promising key signaling pathways, targets, and bioactives of CS against obesity, suggesting crucial pharmacological evidence for further clinical testing.     

Protective effects of cinnamon powder against hyperlipidemia and hepatotoxicity in butter fed female albino mice

A butter-enriched high-fat diet changes lipid metabolism, resulting in fat storage, hyperlipidemia and obesity. Effects of cinnamon powder were investigated in butter-fed mice. 40 Swiss Albino mice, aged 28 to 30 days, were randomly assigned into two groups. Group A was an untreated control group (n = 8) and another group (n = 32) was a butter-treated group fed 10% butter. In the fifth week, mice of the butter-fed group were further divided into four equal groups: B, C, D, and E (n = 8), fed 10% butter with cinnamon 200 mg, 400 mg, and 600 mg powder per liter drinking water, respectively for 10 weeks. The butter-fed group was gained the most weight. Cinnamon supplementation significantly normalized weight gain and had no harmful effects on hematological parameters. Butter supplementation significantly increased total cholesterol (TC), triglycerides, and LDL cholesterol (LDL-c) whereas, cinnamon powder significantly reduced TC, LDL-c and glucose levels. In butter-fed mice, a significant increase was observed in the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with subsequent fat deposition in the liver. Excitingly, these enzymes were decreased and no fat depositions were observed in the liver of cinnamon-treated mice. Applying different concentrations of cinnamon powder improved the lipid profile in butter-fed female albino mice.