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AbstractThe eye is a vital organ in the visual system, which is composed of transparent vascular tissue. αB-crystallin, a significant protein found in the lens, plays a crucial role in our understanding of lens diseases. Mutations in the αB-crystallin protein can cause lens diseases, such as cataracts and myopathy. However, the molecular mechanism underlying the R120G mutation is not fully understood. In this study, we utilized molecular dynamics simulations to illustrate, in atomic detail, how the R120G mutation leads to the aggregation of αB-crystallin and scattering of light in the lens. Our findings show that the R120G mutation alters the dynamic and structural properties of the αB-crystallin protein. Specifically, this mutation causes the angle of the hairpin at the C-terminal to increase from 80° to 150°, while reducing the distance between the hydrophobic patches around residues 10 and 44-55 from 1.5 nm to 1 nm. In addition, our results showed that the mutation could disrupt the IPI motif - β4/β8 interaction. The disruption of this interaction could affect the αB-crystallin oligomerization and the chaperone activity of αB-crystallin protein. The exposed hydrophobic area at the IPI motif - β4/β8 could become the primary site for interprotein interactions, which are responsible for large-scale aggregation. We have demonstrated that, in wild-type αB-crystallin protein, salt bridges R120 and D109, R107 and D80 are formed. However, in the case of the R120G mutation, the salt bridges R120 and R109 are disrupted, and a new salt bridge with a different pattern is formed. In our study, it has been found that all of the changes associated with the R120G mutation are located at the interface of chains A and B, which could impact the multimerization of the αB-crystallin. Previous research on the K92-E99 residue has shown that a salt bridge in the dimer I can reduce the chaperone activity of the protein. Furthermore, the salt bridges R120 and D109, as well as R107 and D80 in dimer II, induce changes in the hydrophobic envelope of β-sheets in the α-crystallin domain (ACD). These changes could have an impact on the multimerization of the αB-crystallin, leading to disruption of the oligomer structure and aggregation. Moreover, the changes in the αB-crystallin resulting from the R120G mutation can lead to faulty interactions with other proteins, which can cause the aggregation of αB-crystallin with other proteins, such as desmin. These findings may provide new insights into the development of treatments for lens diseases.Communicated by Ramaswamy H. Sarma

Neurodegenerative diseases mainly affect the vital characteristics of neurons, including axons. The fabricated nanotopographies can cause axonal regeneration manipulating the migration and differentiation of cells. Here, we present a protocol for the fabrication of nanosubstrate incorporated with nanogroove topography with a coated layer of polyaniline-chitosan (PANI-C) nanocomposite. We describe steps for investigating differences between bulk polydimethylsiloxane (PDMS) sheets and embedding sheets with nanogrooves. We then detail procedures for coating with a PANI-C nanocomposite layer on the substrate.

AbstractThe β42amyloid peptides (Aβ) are identified as a candidate target for Alzheimer’s drugs. Phenolic compounds can bind to the Aβ and inhibit amyloid formation. However, the inhibitory mechanism of phenolic compounds remains unclear. In this study, the molecular dynamic simulation and docking program were used to characterize the molecular details of inhibitory mechanism of the phenolic compounds. Our Results show that the phenolic compounds can bind to hydrophobic region in Aβ42monomer and alter hydrophobic interactions network at Aβ42which play a key role in β-sheet formation. The cluster analysis and interactions network analysis were used to probe conformational changes in Aβ42. In most populated clusters of Aβ42-phenolic compounds complexes, the sheet structures were not observed or reduced. It seems that the binding of phenolic compounds can induce larger conformational diversity for amyloid peptide and changes conformational properties of amyloid peptide. The phenolic compounds can deform β-Hairpin structure of Aβ by destabilizing salt bridges E22-K28 and D23-K28 which can alter the conformation of Aβ42in aqueoussolution. These findings are in accordance with experimental results, to some extent give a molecular level interpretation for the inhibitory mechanism of phenolic compounds .In addition, this study may add important new details to the inhibitory mechanism of Alzheimer’s drug.Communicated by Ramaswamy H. Sarma

•HRSEM and AFM confirmed the FTO surface has been modified as a robust biosensor.•By surfactant/stabilizer-free gold nanostructures on the FTO electrodes, is able to sense ultra-low level of microRNAs.•Our gold nanostructure surface is able to detect miR-9 at zepto molar level by electrochemistry approach.

•Graphene oxide nano-wall decorated with gold nano-flower shape nanoparticle fabricated on the FTO surfaces.•The brucellosis outer membrane protein is immobilized on a fabricated nanostructure as a capture probe to detect the brucellosis antibodies.•The biosensor has a strong ability to detect brucellosis antibodies even in human serum.•Excellent specificity of the biosensor to distinguish brucellosis antibodies from non-specific targets was achieved.

The nucleosome core particle (NCP) is the basic building block of chromatin. Nucleosome-nucleosome interactions are instrumental in chromatin compaction, and understanding NCP self-assembly is important for understanding chromatin structure and dynamics. Recombinant NCPs aggregated by multivalent cations form various ordered phases that can be studied by x-ray diffraction (small-angle x-ray scattering). In this work, the effects on the supramolecular structure of aggregated NCPs due to lysine histone H4 tail acetylations, histone H2A mutations (neutralizing the acidic patch of the histone octamer), and the removal of histone tails were investigated. The formation of ordered mainly hexagonal columnar NCP phases is in agreement with earlier studies; however, the highly homogeneous recombinant NCP systems used in this work display a more compact packing. The long-range order of the NCP columnar phase was found to be abolished or reduced by acetylation of the H4 tails, acidic patch neutralization, and removal of the H3 and H2B tails. Loss of nucleosome stacking upon removal of the H3 tails in combination with other tails was observed. In the absence of the H2A tails, the formation of an unknown highly ordered phase was observed.

Radicals at work: Radical‐mediated thiol‐ene addition of the thiol group of Cys to N‐vinylacetamide gives acetyl‐thialysine (KSAc), a near‐perfect mimic of acetyl‐lysine (see picture). The reaction is highly efficient with near quantitative conversion obtained in short reaction times. The generated KSAc is functionally identical or similar to its native counterpart.

Radikale am Werk: Die radikalvermittelte Thiol‐En‐Addition der Thiolgruppe von Cys an N‐Vinylacetamid ergibt Acetylthialysin (KSAc), ein nahezu perfektes Acetyllysin‐Imitat (siehe Bild). Die Reaktion ist hocheffizient mit nahezu quantitativer Umsetzung nach kurzen Reaktionszeiten. Das gebildete KSAc ist zu seinem natürlichen Gegenstück funktional identisch oder ihm sehr ähnlich.

The physical mechanism of the folding and unfolding of chromatin is fundamentally related to transcription but is incompletely characterized and not fully understood. We experimentally and theoretically studied chromatin compaction by investigating the salt-mediated folding of an array made of 12 positioning nucleosomes with 177 bp repeat length. Sedimentation velocity measurements were performed to monitor the folding provoked by addition of cations Na+, K+, Mg2+, Ca2+, spermidine3+, Co(NH3)63+, and spermine4+. We found typical polyelectrolyte behavior, with the critical concentration of cation needed to bring about maximal folding covering a range of almost five orders of magnitude (from 2 μM for spermine4+to 100 mM for Na+). A coarse-grained model of the nucleosome array based on a continuum dielectric description and including the explicit presence of mobile ions and charged flexible histone tails was used in computer simulations to investigate the cation-mediated compaction. The results of the simulations with explicit ions are in general agreement with the experimental data, whereas simple Debye-Hückel models are intrinsically incapable of describing chromatin array folding by multivalent cations. We conclude that the theoretical description of the salt-induced chromatin folding must incorporate explicit mobile ions that include ion correlation and ion competition effects.

MicroRNAs (miRs) as biomarkers for early cancer diagnostic, were detected through a developed ultrasensitive electrochemical biosensor containing gold Nano-islands (Au-NIs) structures. Different concentrations of miR-21 (from zepto -molar to micro range) in both standard solution and blood serum samples were measured to test the sensitivity of biosensor. A high surface-area-to-volume ratio of nanostructures embellished on the FTO electrodes increases the chance of immobilization of the thiol modified capture probe (anti-miR-21 or cap-21). The Au-nanostructures surface modification and its ability to hybridize successfully and stably anti-miR-21 and miR-21 confirmed by electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV) electrochemical techniques. The results showed that the linear detection range of the biosensor was from 1.0 zM to 200 nM with a limit of detection (LOD) of 0.12 zM which revealed a very high sensitivity. The selectivity of the biosensor was also investigated and confirmed by detecting miR-9 and miR-486. Corresponding results revealed that the biosensor discriminated target miR-21 from non-complementary miR-21 and showed high selectivity and specificity. Our results also revealed that this platform is a promising substrate to quantitative analysis of miR-21 in physiological samples and could be used for biomedical research and point-of-care (POC) diagnosis. Straightforward and robust Au-NIs surface fabricated without surfactant and stabilizer additive, with plenty of anchors for ssDNA immobilization, as well as well-established hybridization and immobilization procedures, plus high electron transfer rate ability in comparison to bare FTO electrodes are among attractive and suitable novelty of this study.