Identification and Investigation of a Cryptic Binding Pocket of the P37 Envelope Protein of Monkeypox Virus by Molecular Dynamics Simulations.

The spread of the monkeypox virus has surged during the unchecked COVID-19 epidemic. The most crucial target is the viral envelope protein, p37. However, lacking p37's crystal structure is a significant hurdle to rapid therapeutic discovery and mechanism elucidation. Structural modeling and molecular dynamics (MD) of the enzyme with inhibitors reveal a cryptic pocket occluded in the unbound structure. For the first time, the inhibitor's dynamic flip from the active to the cryptic site enlightens p37's allosteric site, which squeezes the active site, impairing its function. A large force is needed for inhibitor dissociation from the allosteric site, ushering in its biological importance. In addition, hot spot residues identified at both locations and discovered drugs more potent than tecovirimat may enable even more robust inhibitor designs against p37 and accelerate the development of monkeypox therapies.

Haar wavelet transform-based optimal Bayesian method for medical image fusion.

Image fusion (IF) attracts the researchers in the areas of the medical industry as valuable information could be afforded through the fusion of images that enable the clinical decisions to remain effective. With the aim to render an effective image fusion, this paper concentrates on the Bayesian fusion approach, which is tuned optimally using the proposed Fractional Bird Swarm Optimization (Fractional-BSA). The medical image fusion is progressed using the MRI brain image taken from the BRATS database, and the source images of multimodalities are fused effectively to present an information-rich fused image. The source images are subjected to the Haar wavelet transform, and the Bayesian fusion is performed using the Bayesian parameter, which is determined optimally using the proposed Fractional-BSA optimization. The proposed optimization is the integration of the fractional theory in the standard Bird Swarm Optimization (BSA), which improves the effectiveness of image fusion. Unlike any other existing methods, the proposed Fractional-BSA-based Bayesian Fusion approach renders a good quality and complex-free fusion experience. The analysis reveals that the method outperformed the existing methods with maximal mutual information, maximal peak signal-to-noise ratio (PSNR), minimal root mean square error (RMSE) of 1.5665, 44.0857 dB, and 5.4840, respectively. Graphical abstract Schematic diagram of medical image fusion Medical IF is the significant research domain, which affords the fused image in such a way that this image carries a greater availability of the information content regarding any scene than the information carried by the single source image. Moreover, the concept of fusing multimodality enhances the contents in the image, which increases the reliability and overall information of the image. Thus, the efficient representation of the input data is made through the medical IF such that the physicians are assisted with a wide range of data for effective decision-making. Thus, the paper deals with the medical IF based on the Bayesian fusion approach for which the variable modalities of the image are used. The input image considered is the MRI brain image with four modalities, Flair, T2, T1, and T1C. Among the four modalities, any of the two modalities are considered the source images for fusion. The first step in IF is the generation of the wavelet coefficients, low-low (LL), high-low (HL), low-high (LH), and high-high (HH) using the Haar wavelet transform. Upon deriving the wavelet coefficients, the wavelets are fused based on the Bayesian fusion, which is progressed based on the proposed Fractional-BSA. Once the fused bands are formed, the inverse Haar wavelet transform generates the fused image, and it is significant to note that the IF is performed at the pixel level in such a way that the image quality is assured with a high level of the information for clinical applications. The advantages of the pixel-level fusion are regarding the original measured quantities, which involve directly in the fusion process.

Immunobiological activities of a new nontoxic lipopolysaccharide from Acidiphilium GS18h/ATCC55963, a soil isolate from an Indian copper mine.

A novel nontoxic lipopolysaccharide (LPS) was purified from Acidiphilium strain GS18h/ATCC55963. The chemical composition of the lipid A part of this LPS is distinctly different from that of known lipid A molecules. The LPS was investigated to determine its capacity to provide protection against toxic LPS or endotoxic shock, as has been reported for other nontoxic LPSs (Rhodobacter sphaeroides and Rhodobacter capsulatus), and also the extent and type of immunomodulatory response in terms of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-beta), and IL-6 release as well as NO secretion by stimulated monocyte-macrophage systems. This study demonstrates clearly that mice immunized or primed with this LPS are fully protected against challenge with toxic Escherichia coli LPS. Unlike most of the extensively studied nontoxic LPSs, this LPS induced reactive nitrogen intermediates and released TNF-alpha, IL-beta and IL-6 in both mouse and human monocyte-macrophage systems. However, the extent of the cytokine and lymphokine releasing response was well below the range of the toxic LPS, for example that of E. coli. Owing to its capacity to provide immunostimulation of the host without causing any lethality to ensure protection against endotoxic shock, this LPS appears to have potential therapeutic value.

Isolation and characterisation of the lipopolysaccharide from Acidiphilium strain GS18h/ATCC55963, a soil isolate of Indian copper mine.

The lipopolysaccharide (LPS) of the Gram-negative Acidiphilium strain GS18h/ATCC55963, a new soil isolate, exhibited very low endotoxic activity as determined by Limulus gelation activity, lethal toxicity in galactosamine (GalN) sensitised mice, and level of tumor necrosis factor alpha (TNFalpha) in the blood serum of BALB/c mice. Analysis of the LPS, specially of lipid A which usually accounts for the toxicity, revealed the latter to contain glucosamine and phosphate besides fatty acids, of which 14:0(3-OH), 18:0(3-OH), 18:1 and 19:0(cyclo) are the major components, while 12:0, 16:0, 19:1, 20:0(3-OH) and 20:1(3-OH) are present in small amounts. The 14:0(3-OH) and 18:0(3-OH) fatty acids are amide-linked, whereas the rest are ester bound. Glucose, galactose, mannose, rhamnose, heptose, galacturonic acid and 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) were present in the polysaccharide part of this LPS. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the LPS showed a macromolecular heterogeneity distinctly different from those of Escherichia coli or Salmonella. The toxicity of this LPS being extremely low attributed to fatty acid composition of its lipid A, promises potential therapeutic application.