Computational Design and Analysis of a Multi-epitope Against Influenza A virus

International Journal of Peptide Research and Therapeutics - Influenza A viruses are among the most studied viruses, however no effective prevention against influenza infection has been developed....     

A Tunable Perfect THz Metamaterial Absorber with Three Absorption Peaks Based on Nonstructured Graphene

In this paper, a graphene-based tunable multi-band terahertz absorber is proposed and numerically investigated. The proposed absorber can achieve perfect absorption within both sharp and ultra-broadband absorption spectra. This wide range of absorption is gathered through a unique combination of periodically cross- and square-shaped dielectrics sandwiched between two graphene sheets; the latter enables it to offer more absorption in comparison with the traditional single-layer graphene structures. The aforementioned top layer is mounted on a gold plate separated by a Topas layer with zero volume loss. Furthermore, in our proposed approach, we investigated the possibility of changing the shapes and sizes of the dielectric layers instead of the geometry of the graphene layers to alleviate the edge effects and manufacturing complications. In numerical simulations, parameters, such as graphene Fermi energy and the dimensions of the proposed dielectric layout, have been optimally tuned to reach perfect absorption. We have verified that the performance of our dielectric layout called fishnet, with two widely investigated dielectric layouts in the literature (namely, cross-shaped and frame-and-square). Our results demonstrate two absorption bands with near-unity absorbance at frequencies of 1.6–2.3 and 4.2–4.9 THz, with absorption efficiency of 98% in 1.96 and 4.62 THz, respectively. Moreover, a broadband absorption in the 7.77–9.78 THz is observed with an absorption efficiency of 99.6% that was attained in 8.44–9.11 THz. Finally, the versatility provided by the tunability of three operation bands of the absorber makes it a great candidate for integration into terahertz optoelectronic devices.

     

Dynamic Bis-Intercalation of a Homodimeric Thiazole Orange Dye in DNA: Evidence of Intercalator Creeping

Abstract

We have used one and two dimensional exchange ¹H NMR spectroscopy to characterize the dynamics of the binding of a homodimeric thiazole orange dye, 1,1′-(4,4,8,8-tetramethyl-4,8-diaza-undecamethylene)-bis-4-(3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolinium tetraiodide (TOTO), to double stranded DNA (dsDNA). The double stranded oligonucleotides used were d-(CGCTAGCG)₂ ( 1 ) and d(CGCTAGCTAGCG)₂ ( 2 ). TOTO binds preferentially to the (5′-CTAG-3′)₂ sites and forms mixtures of 1:1 and 1:2 dsDNA-TOTO complexes with 2 in ratios dependent on the relative amount of TOTO and the oligonucleotide in the sample. The dynamic exchange between preferential binding sites in the case of a 2:1 1 -TOTO mixture is an intermolecular exchange process between two binding sites on different oligonucleotides. In the case of the 1:1 2 -TOTO complex an intramolecular exchange process occur between two different binding sites on the same strand. Both processes were studied. The results demonstrate the ability of TOTO to migrate along a dsDNA strand in an intramolecular exchange process. The migration process (“creeping”) along the DNA strand is 6 times faster than the rate of intermolecular exchange between sites in two different oligonucleotides.     

The Biosynthetic Origin of Irregular Monoterpenes in Lavandula: ISOLATION AND BIOCHEMICAL CHARACTERIZATION OF A NOVEL cis-PRENYL DIPHOSPHATE SYNTHASE GENE,LAVANDULYL DIPHOSPHATE SYNTHASE*

Lavender essential oils are constituted predominantly of regular monoterpenes, for example linalool, 1,8-cineole, and camphor. However, they also contain irregular monoterpenes including lavandulol and lavandulyl acetate. Although the majority of genes responsible for the production of regular monoterpenes in lavenders are now known, enzymes (including lavandulyl diphosphate synthase (LPPS)) catalyzing the biosynthesis of irregular monoterpenes in these plants have not been described. Here, we report the isolation and functional characterization of a novel cis-prenyl diphosphate synthase cDNA, termed Lavandula x intermedia lavandulyl diphosphate synthase (LiLPPS), through a homology-based cloning strategy. The LiLPPS ORF, encoding for a 305-amino acid long protein, was expressed in Escherichia coli, and the recombinant protein was purified by nickel-nitrilotriacetic acid affinity chromatography. The approximately 34.5-kDa bacterially produced protein specifically catalyzed the head-to-middle condensation of two dimethylallyl diphosphate units to LPP in vitro with apparent K_m and k_cat values of 208 ± 12 μm and 0.1 s⁻¹, respectively. LiLPPS is a homodimeric enzyme with a sigmoidal saturation curve and Hill coefficient of 2.7, suggesting a positive co-operative interaction among its catalytic sites. LiLPPS could be used to modulate the production of lavandulol and its derivatives in plants through metabolic engineering.     

Agonist Leukadherin-1 Increases CD11b/CD18-Dependent Adhesion Via Membrane Tethers

Integrin CD11b/CD18 is a key adhesion receptor that mediates leukocyte migration and immune functions. Leukadherin-1 (LA1) is a small molecule agonist that enhances CD11b/CD18-dependent cell adhesion to its ligand ICAM-1. Here, we used single-molecule force spectroscopy to investigate the biophysical mechanism by which LA1-activated CD11b/CD18 mediates leukocyte adhesion. Between the two distinct populations of CD11b/CD18:ICAM-1 complex that participate in cell adhesion, the cytoskeleton(CSK)-anchored elastic elements and the membrane tethers, we found that LA1 enhanced binding of CD11b/CD18 on K562 cells to ICAM-1 via the formation of long membrane tethers, whereas Mn²⁺ additionally increased ICAM-1 binding via CSK-anchored bonds. LA1 activated wild-type and LFA1^−/− neutrophils also showed longer detachment distances and time from ICAM-1-coated atomic force microscopy tips, but significantly lower detachment force, as compared to the Mn²⁺-activated cells, confirming that LA1 primarily increased membrane-tether bonds to enhance CD11b/CD18:ICAM-1 binding, whereas Mn²⁺ induced additional CSK-anchored bond formation. The results suggest that the two types of agonists differentially activate integrins and couple them to the cellular machinery, providing what we feel are new insights into signal mechanotransduction by such agents.     

Novel strategies for inhibition of bacterial biofilm in chronic rhinosinusitis

An important role has been recently reported for bacterial biofilm in the pathophysiology of chronic diseases, such as chronic rhinosinusitis (CRS). CRS, affecting sinonasal mucosa, is a persistent inflammatory condition with a high prevalence around the world. Although the exact pathological mechanism of this disease has not been elicited yet, biofilm formation is known to lead to a more significant symptom burden and major objective clinical indicators. The high prevalence of multidrug-resistant bacteria has severely restricted the application of antibiotics in recent years. Furthermore, systemic antibiotic therapy, on top of its insufficient concentration to eradicate bacteria in the sinonasal biofilm, often causes toxicity, antibiotic resistance, and an effect on the natural microbiota, in patients. Thus, coming up with alternative therapeutic options instead of systemic antibiotic therapy is emphasized in the treatment of bacterial biofilm in CRS patients. The use of topical antibiotic therapy and antibiotic eluting sinus stents that induce higher antibiotic concentration, and decrease side effects could be helpful. Besides, recent research recognized that various natural products, nitric oxide, and bacteriophage therapy, in addition to the hindered biofilm formation, could degrade the established bacterial biofilm. However, despite these improvements, new antibacterial agents and CRS biofilm interactions are complicated and need extensive research. Finally, most studies were performed in vitro, and more preclinical animal models and human studies are required to confirm the collected data. The present review is specifically discussing potential therapeutic strategies for the treatment of bacterial biofilm in CRS patients.     

Taxonomic status of the loaches Paracobitis vignai and P. rhadinaea (Teleostei: Nemacheilidae) in Iran

The crested loaches of the genus Paracobitis from the Sistan basin (Iran) are reviewed based on morphological and mitochondrial cytb and COI sequences characters to check the status of taxa in phylogenetic trees. Paracobitis rhadinaea (Regan, 1906) and P. vignai Nalbant & Bianco, 1998 were known only based on minor morphological differences (presence or absence of scales, caudal fin shape, colour pattern and fish size). We failed to find any diagnostic molecular and morphological characters between them. Therefore, we regard P. vignai as a junior synonym of P. rhadinaea.