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The spermatozoa are transcriptionally dormant entities which have been recognized to be an archive of mRNA, coding for a variety of functionally crucial cellular proteins. This significant repository of mRNA is predicted to be associated with early embryogenesis and postfertilization. The mRNA transcripts which are tagged with minisatellites have been involved in the regulation of the gene functions as well as their organization. However, very little information is available regarding the expression of the transcripts tagged with minisatellites in spermatozoa. Therefore, in order to understand the functions and the conformational behavior of the proteins expressed from these minisatellite-tagged transcripts, we have performed a detailed in silico analysis using the sequences of the transcripts. The protein predicted from KF274549 showed the functionalities similar to uncharacterized C4orf26 proteins, while that obtained from KF274557 predicted to be a metallophosphoesterase. Furthermore, the structural folds in the structure of these predicted proteins were analyzed by using the homology modeling and their conformational behaviors in the explicit water conditions were analyzed by using the techniques of Molecular Dynamics (MD) simulations. This detailed analysis will facilitate the understanding of these proteins in the spermatozoon region and can be used for uncovering other attributes of the metabolic network. [ABSTRACT FROM AUTHOR]

Rab proteins belong to the family of monomeric GTPases which are involved in the cellular membrane trafficking. Rab21 protein exists in interchangeable GTP- and GDP-bound states. Rabs switch between two active and inactive conformations like other GTPases. The inactive form of Rab is bound to GDP while its active form is bounded with the GTP. Interexchange between active and inactive form is mediated by the GDP/GTP exchange factor (GEF) which catalyses the conversion from GDP-bound to GTP-bound form, thereby activating the Rab. While the GTP hydrolysis of Rabs is regulated by a GTPase-activating protein (GAP) which causes Rab inactivation. Here, we report the structural flexibility of the Rab21-GTP and Rab21-GDP complexes by docking and molecular dynamics (MD) simulations. Structural analysis of exchange mechanisms of the co-factors complexed with Rab21 reveals that Cys29, Thr33, His48, Gln78 and Lys133 are essentially important in the activation of proteins. Furthermore, a significant change in the orientation of the interacting co-factors, with slight variation in the free energy of binding was observed. Complexation of GEF with Rab21-GTP and Rab21-GDP reveal a flipping of the switchable residues. Finally, 50 ns MD simulations confirm that the GTP-bound Rab21 complex is thermodynamically more favoured than the corresponding GDP-bound complex. This study provides a detailed understanding of the structural elements involved in the conformational changes of Rab21. [ABSTRACT FROM PUBLISHER]

Neisseria meningitidis is a Gram-negative aerobic diplococcus, responsible for a variety of meningococcal diseases. The genome of N. meningitidis MC58 is comprised of 2114 genes that are translated into 1953 proteins. The 698 genes (∼35%) encode hypothetical proteins (HPs), because no experimental evidence of their biological functions are available. Analyses of these proteins are important to understand their functions in the metabolic networks and may lead to the discovery of novel drug targets against the infections caused by N. meningitidis. This study aimed at the identification and categorization of each HP present in the genome of N. meningitidis MC58 using computational tools. Functions of 363 proteins were predicted with high accuracy among the annotated set of HPs investigated. The reliably predicted 363 HPs were further grouped into 41 different classes of proteins, based on their possible roles in cellular processes such as metabolism, transport, and replication. Our studies revealed that 22 HPs may be involved in the pathogenesis caused by this microorganism. The top two HPs with highest virulence scores were subjected to molecular dynamics (MD) simulations to better understand their conformational behavior in a water environment. We also compared the MD simulation results with other virulent proteins present in N. meningitidis. This study broadens our understanding of the mechanistic pathways of pathogenesis, drug resistance, tolerance, and adaptability for host immune responses to N. meningitidis. [ABSTRACT FROM AUTHOR]

Haemophilus influenzae is a Gram negative bacterium that belongs to the family Pasteurellaceae, causes bacteremia, pneumonia and acute bacterial meningitis in infants. The emergence of multi-drug resistance H. influenzae strain in clinical isolates demands the development of better/new drugs against this pathogen. Our study combines a number of bioinformatics tools for function predictions of previously not assigned proteins in the genome of H. influenzae. This genome was extensively analyzed and found 1,657 functional proteins in which function of 429 proteins are unknown, termed as hypothetical proteins (HPs). Amino acid sequences of all 429 HPs were extensively annotated and we successfully assigned the function to 296 HPs with high confidence. We also characterized the function of 124 HPs precisely, but with less confidence. We believed that sequence of a protein can be used as a framework to explain known functional properties. Here we have combined the latest versions of protein family databases, protein motifs, intrinsic features from the amino acid sequence, pathway and genome context methods to assign a precise function to hypothetical proteins for which no experimental information is available. We found these HPs belong to various classes of proteins such as enzymes, transporters, carriers, receptors, signal transducers, binding proteins, virulence and other proteins. The outcome of this work will be helpful for a better understanding of the mechanism of pathogenesis and in finding novel therapeutic targets for H. influenzae. [ABSTRACT FROM AUTHOR]

The current study was focused on the investigation of anticancer activity of Scindapsus Officinalis fruit extract embedded silver nanoparticles (So -AgNPs) followed by anticovid activity prognosis of major phytocompounds, which participate in nanoformulation synthesis. The synthesis process involved the addition of AgNO 3 solution (1 mM) and color change of the extract from light brown to dark, confirmed the formation of silver nanoparticles. Further, the characterization of synthesized So -AgNPs were done using different spectroscopical and microscopical techniques. FTIR spectra of So-AgNPs indicated vibrational peaks of polyphenolic hydroxyl groups, which are responsible for the stabilization of nanoformulation. Others microscopy methods such as SEM, TEM, XRD, and EDX illustrated that the synthesized So-AgNPs consist irregular size, spherical shape and thoroughly dispersed above the plane. Anticancer evaluation illustrated that the So-AgNPs have dose dependent anti-breast and anti-hepatic cancer activity (range of 97.72 ± 0.42–54.86 ± 0.46% cell viability), which were noticed more effective than raw fruit extract of Scindapsus Officinalis. The computational anticovid prediction of major phyto-compound of the extract [which designate as inhibitor 1: ((2R,3S,4S, 5R)-2-(hydroxymethyl)-6-(((1S, 5S)-1-methyl-5-(2-methylprop-1-en-1-yl)cyclopent-2-en-1-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol)] illustrated moderate tendency to interact with corona main protease enzyme (expected pIC > 6 μM). However, the molecular docking and dynamics studies showed that selected compounds have moderate tendency to interact human dihydrofolate reductase and topoisomerase 1 enzyme. The accomplished approach shows that So -AgNPs with adsorbed phytocompounds on its surface consist valuable experimentally proved anticancer potency and computationally predicted anticovid effect. Thus, the formulation can be used as an alternative to the covid infected cancer population. [Display omitted] •Green synthesis of Scindapsus Officinalis stabilized silver nanoparticles. • So -AgNPs showed significant activity against r cancer cells. • SO-AgNPs shows significant specificity and nontoxic effect against two non-cancerous cell lines. [ABSTRACT FROM AUTHOR]

The photocatalytic activities of TiO2 have been limited mainly to absorbing in the ultraviolet spectrum which accounts for only 5% of solar radiation. High energy band gap and electron recombination in TiO2 nanoparticles are responsible for its limitations as a photocatalyst. An oxygen deficient surface can be artificially created on the titanium oxide by zero valent nano iron through the donation of its excess electrons. A visible light active TiO2 nanoparticle was synthesized in the current investigation through simple chemical reduction using sodium boro-hydride. The physical and textural properties of the synthesized oxygen deficient TiO2 photocatalyst was measured using scanning/ transmission electron microscopy while FTIR, XRD and nitrogen sorption methods (BET) were employed for its further characterizations. Photochemical decoloration of orange II sodium dye solution in the presence of the synthesized TiO2 was measured using an UV spectrophotometer. The resulting oxygen deficient TiO2 has a lower energy band-gap, smaller pore sizes, and enhanced photo-catalytic properties. The decoloration (88%) of orange (II) sodium salt solution (pH 2) under simulated solar light was possible at 20 min. This study highlights the effect of surface oxygen defects, crystal size and energy band-gap on the photo-catalytical property of TiO2 nanoparticles as impacted by nano zero valent iron. It opens a new window in the exploitation of instability in the dopant ions for creation of a visible light active TiO2 photocatalyst. [ABSTRACT FROM AUTHOR]

To describe a case of Alternaria keratitis in a 30-year-old male patient who presented with bilateral vascularised central corneal opacity and underwent deep anterior lamellar keratoplasty (DALK) in the left eye. Patient was treated for recurrent epithelial defect with a bandage contact lens in the follow-up visits after DALK. Subsequently, patient presented with pigmented fungal keratitis, which on culture examination of the corneal scrapping demonstrated Alternaria species. Patient had to undergo a repeat DALK as the keratitis did not resolve with medical therapy alone. Patient did not have a recurrence for 11 months following the regraft. This case report highlights the importance of considering the Alternaria species as a possibile cause of non-resolving fungal keratitis after DALK. [ABSTRACT FROM AUTHOR]

Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CP Exo ) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CP Exo instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CP Exo has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Drug development for common complex diseases is in need of new molecular entities and actionable drug targets. MAP/microtubule affinity-regulating kinase 4 (MARK4) is associated with numerous diseases such as neurodegenerative disorders, obesity, cancer, and type 2 diabetes. Understanding the structural basis of ligands' (inhibitors) and substrates' binding to MARK4 is crucial to design new kinase inhibitors for therapeutic purposes. This study reports new observations on docking three well-known kinase inhibitors in the kinase domain of MARK4 variants and the calculated binding affinity. These variants of MARK4 are named as MARK4-F1 (59 N-terminal residues along with kinase domain) and MARK4-F2 (kinase domain of MARK4). We additionally performed molecular dynamics (MD) simulation and fluorescence binding studies to calculate the actual binding affinity of kinase inhibitors, BX-912, BX-795, and OTSSP167 (hydrochloride) for the MARK4. Docking analyses revealed that ligands bind in the large hydrophobic cavity of the kinase domain of MARK4 through several hydrophobic and hydrogen-bonded interactions. Simulations suggested that OTSSP167 (hydrochloride) is forming a stable complex, and hence the best inhibitor of MARK4. Intrinsic fluorescence of MARK4 was significantly quenched by addition of ligands, indicating their potential binding to MARK4. A lower KD value of MARK4 with OTSSP167 (hydrochloride) suggested that it is a better interacting partner than BX-912 and BX-795. These data form a basis for designing novel and potent OTSSP167 (hydrochloride) derivatives as therapeutic candidates against common complex diseases. The inhibitors designed as such might possibly suppress the growth of tumor-forming cells and be potentially applied for treatment of a wide range of human cancers as well.

Haemophilus influenzae is a Gram negative bacterium that belongs to the family Pasteurellaceae, causes bacteremia, pneumonia and acute bacterial meningitis in infants. The emergence of multi-drug resistance H. influenzae strain in clinical isolates demands the development of better/new drugs against this pathogen. Our study combines a number of bioinformatics tools for function predictions of previously not assigned proteins in the genome of H. influenzae. This genome was extensively analyzed and found 1,657 functional proteins in which function of 429 proteins are unknown, termed as hypothetical proteins (HPs). Amino acid sequences of all 429 HPs were extensively annotated and we successfully assigned the function to 296 HPs with high confidence. We also characterized the function of 124 HPs precisely, but with less confidence. We believed that sequence of a protein can be used as a framework to explain known functional properties. Here we have combined the latest versions of protein family databases, protein motifs, intrinsic features from the amino acid sequence, pathway and genome context methods to assign a precise function to hypothetical proteins for which no experimental information is available. We found these HPs belong to various classes of proteins such as enzymes, transporters, carriers, receptors, signal transducers, binding proteins, virulence and other proteins. The outcome of this work will be helpful for a better understanding of the mechanism of pathogenesis and in finding novel therapeutic targets for H. influenzae.