D936Y and Other Mutations in the Fusion Core of the SARS-CoV-2 Spike Protein Heptad Repeat 1: Frequency,Geographical Distribution,and Structural Effect

The crown of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constituted by its spike (S) glycoprotein. S protein mediates the SARS-CoV-2 entry into the host cells. The “fusion core” of the heptad repeat 1 (HR1) on S plays a crucial role in the virus infectivity, as it is part of a key membrane fusion architecture. While SARS-CoV-2 was becoming a global threat, scientists have been accumulating data on the virus at an impressive pace, both in terms of genomic sequences and of three-dimensional structures. On 15 February 2021, from the SARS-CoV-2 genomic sequences in the GISAID resource, we collected 415,673 complete S protein sequences and identified all the mutations occurring in the HR1 fusion core. This is a 21-residue segment, which, in the post-fusion conformation of the protein, gives many strong interactions with the heptad repeat 2, bringing viral and cellular membranes in proximity for fusion. We investigated the frequency and structural effect of novel mutations accumulated over time in such a crucial region for the virus infectivity. Three mutations were quite frequent, occurring in over 0.1% of the total sequences. These were S929T, D936Y, and S949F, all in the N-terminal half of the HR1 fusion core segment and particularly spread in Europe and USA. The most frequent of them, D936Y, was present in 17% of sequences from Finland and 12% of sequences from Sweden. In the post-fusion conformation of the unmutated S protein, D936 is involved in an inter-monomer salt bridge with R1185. We investigated the effect of the D936Y mutation on the pre-fusion and post-fusion state of the protein by using molecular dynamics, showing how it especially affects the latter one.     

Enhanced energy storage of alkali (Li,Na) titanates by sucrose carbonization

Journal of Solid State Electrochemistry - In this work, a simple and effective synthesis procedure was performed in order to prepare hybrid alkali titanate materials, as negative electrodes for...     

A current-reuse biomedical amplifier with a NEF < 1

Digital image authenticity is always an imperative question to tackle whenever a digital image is being assessed for its content. Using digital forensic algorithms, the image will be evaluated for various traces left from numerous categories of manipulations including, among others, copy–move operations. Later this is considered an essential block in most digital image forgeries. It results in changing the information incorporated in a scene, hiding information from an image, or emphasizing some parts of the image. In this paper we propose and investigate two main approaches that differ in the feature extraction process in order to detect copy–move traces. In the first method, we use two-dimensional discrete cosine transform. Whereas in the second method, the phase response of Gabor filter is being used. Instead of being applied on the image directly, the two methods are applied over the first, the second or the third principal component of the image after being divided into overlapping blocks. Combining these conditions results in six basic implementations that are investigated under three parameters that must be optimized: block dimension, contrast and similarity thresholds. Results from testing and validation process demonstrate that the highest performance, in terms of false accept rate, is obtained when using Gabor filter associated with the first principal component of the image outperforming a reference method we implemented as well.     

Use of poly[ionic liquid] as a conductive binder in lithium ion batteries

Journal of Solid State Electrochemistry - In the present work, we studied the performance of different new binders based on poly[ionic liquids] (POILs) using a well-known negative electrode...     

Time-scale analysis nonlocal diffusion systems,applied to disease models

The objective of the present paper is to use the well-known Ross–Macdonald models as a prototype, incorporating spatial movements, identifying different time scales and proving a singular perturbation result using a system of local and nonlocal diffusion. This results can be applied to the prototype model, where the vector has a fast dynamics, local in space, and the host has a slow dynamics, nonlocal in space.     

Synthesis of O-Alkyl-3-Dimethylhydrazonothionoesters

O-Alkyl-3-dimethylhydrazonothionoesters were obtained by the reaction of dimethyl-hydrazones of acetone and acetophenone with S-ethyl-O-alkyldithiocarbonates.     

Synthesis of 1,4-Dihydropyridines by Regioselective Additions of Benzylic Zinc Bromides to Pyridinium Salts and Their Aromatizations to 4-Benzylpyridines

Benzylic zinc reagents add with high regioselectivity to 1-(phenoxycarbonyl) salts of methyl nicotinate to yield methyl-1-(phenoxylcarbonyl)-4-benzyl-1,4-dihydronicotinates. The dihydronicotinates on heating with sulfur in decalin afford methyl 4-benzylnicotinates.     

Binding free energy calculations to rationalize the interactions of huprines with acetylcholinesterase

In the present study, the binding free energy of a family of huprines with acetylcholinesterase (AChE) is calculated by means of the free energy perturbation method, based on hybrid quantum mechanics and molecular mechanics potentials. Binding free energy calculations and the analysis of the geometrical parameters highlight the importance of the stereochemistry of huprines in AChE inhibition. Binding isotope effects are calculated to unravel the interactions between ligands and the gorge of AChE. New chemical insights are provided to explain and rationalize the experimental results. A good correlation with the experimental data is found for a family of inhibitors with moderate differences in the enzyme affinity. The analysis of the geometrical parameters and interaction energy per residue reveals that Asp72, Glu199, and His440 contribute significantly to the network of interactions between active site residues, which stabilize the inhibitors in the gorge. It seems that a cooperative effect of the residues of the gorge determines the affinity of the enzyme for these inhibitors, where Asp72, Glu199, and His440 make a prominent contribution.