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Background: Drug-resistant pathogens and industrial dye wastes have emerged as critical global public health concerns, posing significant risks to human and animal health, as well as to environmental sustainability. Green synthesized nano absorbents were found to be a viable strategy for treating drug-resistant pathogens and in wastewater. Hence, this study endeavored the synthesis of piperine-driven nano-zinc oxide (ZnONPs) and evaluated them for antibacterial, antibiofilm, and photocatalytic disinfection potential against multi-drug resistant (MDR) foodborne strains of non-typhoidal Salmonella (NTS). Besides, the dye degradation potential of ZnONPs when exposed to UV, sunlight, and LED lights and their antioxidant capacity were assessed. Results: Initially, in silico analysis of piperine revealed drug-likeliness with minimal toxicity and strong interaction between piperine and OmpC motifs of Salmonella spp. UV spectroscopy of ZnONPs revealed a prominent absorption peak at 340 nm, while PXRD analysis confirmed the hexagonal wurtzite structure of ZnONPs by exhibiting peaks at 30°, 35.6°, 41.3°, 43.6°, 44.3°, 48°, 53°, 58°, and 59.2°, which corresponded to the lattice planes (102), (110), (103), (200), (112), (004), (104), (210), and (211). Additionally, the TEM images demonstrated predominantly spherical ZnONPs with hexagonal wurtzite crystalline SAED pattern. The minimum inhibitory concentration and minimum bactericidal concentration values (µg/mL) of the ZnONPs were found to be 62.50 and 125, respectively. The ZnONPs were observed to be safe with minimal hemolysis (less than 2%) in chicken RBCs, and no cytopathic effects were observed in the MTT assay using HEK cell lines. The NPs were found to be variably stable (high-end temperatures, proteases, cationic salts, and diverse pH), and were tested safe towards commensal gut lactobacilli. Additionally, in vitro time-kill kinetic assay indicated that the MDR-NTS strains were eliminated after co-incubating with ZnONPs for 6 h. The photocatalytic studies exhibited complete bacterial elimination under visible light at 4 h. Interestingly, the ZnONPs significantly inhibited the biofilm formation in the crystal violet staining assay by MDR-NTS strains (P < 0.001) at 24 and 48 h. Besides, a dose-dependent reducing power assay and 2,2′- azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) assay were exhibited. Moreover, ZnONPs significantly degraded methylene blue, crystal violet, and rhodamine-B under different light sources (sunlight, UV light, and LED). Conclusions: This study revealed a sustainable one-pot method of synthesizing ZnONPs from piperine, which might be used as a viable antibacterial candidate with antioxidant, antibiofilm, and photocatalytic properties with eco-friendly implications and wastewater treatment. [ABSTRACT FROM AUTHOR]

Adenosine deaminase acting on RNA1 (ADAR1) catalyzes the C6 deamination of adenosine (A) to produce inosine (I) in regions of RNA with double-stranded (ds) character. This process is known as A-to-I RNA editing. Alternative promoters drive the expression of the Adar1 gene and alternative splicing gives rise to transcripts that encode 2 ADAR1 protein size isoforms. ADAR1 p150 is an interferon (IFN)-inducible dsRNA adenosine deaminase found in the cytoplasm and nucleus, whereas ADAR1 p110 is constitutively expressed and nuclear in localization. Dependent on the duplex structure of the dsRNA substrate, deamination of adenosine by ADAR can be either highly site-selective or nonspecific. A-to-I editing can alter the stability of RNA structures and the coding of RNA as I is read as G instead of A by ribosomes during mRNA translation and by polymerases during RNA replication. A-to-I editing is of broad physiologic significance. Both the production and the action of IFNs, and hence the subsequent interaction of viruses with their hosts, are among the processes affected by A-to-I editing.

Measles virus (MV) deficient in C protein (C(ko)) expression efficiently induces both stress granules (SG) and interferon (IFNβ), whereas isogenic wild-type (WT) and V mutant (V(ko)) viruses do not. We therefore examined the effect of IFNβ pretreatment on SG formation, and the roles played by the IFN-inducible double-stranded (ds) RNA-dependent protein kinase (PKR) and dsRNA adenosine deaminase (ADAR1). SG formation in ADAR1-sufficient cells infected with WT or V(ko) mutant virus was enhanced by IFN treatment and was PKR-dependent. SG formation in C(ko) virus-infected cells was already high without IFN treatment and was not further enhanced by IFN. IFN treatment alone, in the absence of infection, induced SG formation in ADAR1-deficient but not ADAR1-sufficient cells. Type I IFN-induced enhancement in SG formation occurred by a canonical IFN signaling response dependent upon STAT1 and STAT2. These results further establish ADAR1 as a suppressor of the interferon and SG innate immune responses.

This study attempted synthesis and characterization of zinc oxide nanoparticles (ZnO NPs) using the aqueous extract of Piper longum catkin and its in vitro antibacterial efficacy against multi-drug-resistant strains (MDR) of non- typhoidal Salmonella (NTS) spp. (S. enterica Typhimurium and S. Enteritidis). The green synthesized ZnO NPs exhibited an absorbance peak at 340 nm by UV-Vis spectroscopy, which was confirmed by FTIR analysis. The TGA/DTA revealed a progressive thermal degradation of the ZnO NPs between 250 °C and 400 °C; however, good thermal stability was exhibited for annealing temperatures between 900 °C and 1300 °C. The ZnO NPs exhibited hexagonal wurtzite crystalline structure by PXRD analysis, which was further confirmed by electron microscopy. Microbroth dilution technique exhibited an MIC and MBC values of 125 and 250 µg/mL, respectively. Overall, the study demonstrated a facile, eco-friendly method for the synthesis of ZnO NPs, which could be employed as a potential antimicrobial alternative candidate. [ABSTRACT FROM AUTHOR]

Abstract Background Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family. After autoproteolytic cleavage, the CHIKV capsid protein (CP) is involved in RNA binding and assembly of the viral particle. The monomeric CP is approximately 30 kDa in size and is small enough for passive transport through nuclear pores. Some alphaviruses are found to harbor nuclear localization signals (NLS) and transport of these proteins between cellular compartments was shown to be energy dependent. The active nuclear import of cytoplasmic proteins is mediated by karyopherins and their export by exportins. As nuclear and cytoplasmic trafficking may play a role in the life cycle of CHIKV, we have sought to identify nuclear localization and nuclear export signals in CHIKV CP in a virus-free system. Methods EGFP-fusion proteins of CHIKV CP and mutants thereof were created and used to monitor their intracellular localization. Binding of cellular proteins was confirmed in pull-down assays with purified CP using co-immuoprecipitation. Nuclear localization was demonstrated in a virus-free system using fluorescence microscopy. Results Here we show that CHIKV CP is a nuclear-cytoplasmic shuttling protein with an active NLS that binds to karyopherin α (Karα) for its nuclear translocation. We also found that the Karα4 C-terminal NLS binding site is sufficient for this interaction. We further demonstrate that CHIKV CP interacts directly with the export receptor CRM1 to transport this viral protein out of the nucleus via a nuclear export signal (NES). The CHIKV CP NES was mapped between amino acids 143 and 155 of CP. Deduced from in silico analyses we found that the NES has a mode of binding similar to the snurportin-1 CRM1 complex. Conclusions We were able to show that in a virus-free system that the CHIKV capsid protein contains both, a NLS and a NES, and that it is actively transported between the cytoplasma and the nucleus. We conclude that CHIKV CP has the ability to shuttle via interaction with karyopherins for its nuclear import and, vice versa, by CRM1-dependent nuclear export.

Dermatophytosis is a potentially zoonotic superficial skin infection caused by keratin ophilic fungi. Identification of dermatophytes aids in understanding the epidemiology of infections and finding out better treatment modalities. The study aimed to identify dermatophytes in dogs and compare the effectiveness of three different topical drugs for treating dermatophytosis. Molecular identification of dermatophyte isolates obtained on culturing was done by restriction fragment length polymorphism of the amplicon obtained by polymerase chain reaction of the Internal Transcribed Spacer (ITS) region of the recombinant DNA. Thirty of the positive cases were divided into three groups, Group I was treated with shampoo containing 2% each of miconazole chlorhexidine, Group 2 with shampoo containing 4% chlorhexidine, and the third group with lime sulphur dip. Clinical response and fungal colony counts were regularly monitored to assess improvement. Among a total of 30 dermatophyte isolates, 14 Microsporum canis, 8 Trichophyton rubrum, 6 M. gypseum, and 2 Epidermophyton floccosum isolates were identified. Increased occurrence of T. rubrum indicates frequent transmission of dermatophytes from humans to dogs. Shampoo containing 4% chlorhexidine for an average duration of 99 days resulted in a faster cure, compared to the other topical preparations. [ABSTRACT FROM AUTHOR]

The cation‐aromatic database (CAD) is a comprehensive repository of cation‐aromatic motifs found in experimentally determined protein structures, first reported in 2007 [Proteins, 2007, 67, 1179]. The present article is an update of CAD that contains information of approximately 27.26 million cation‐aromatic motifs. CAD uses three distance parameters (r, d1, and d2) to determine the position of the cation relative to the centroid of the aromatic residue and classifies the motifs as cation‐π or cation‐σ interactions. As of June 2023, about 193 936 protein structures were retrieved from Protein Data Bank, and this resulted in the identification of an impressive number of 27 255 817 cation‐aromatic motifs. Among these motifs, spherical motifs constituted 94.09%, while cylindrical motifs made up the remaining 5.91%. When considering the interaction of metal ions with aromatic residues, 965 564 motifs are identified. Remarkably, 82.08% of these motifs involved the binding of metal ions to the amino acid HIS. Moreover, the analysis of binding preferences between cations and aromatic residues revealed that the HIS‐HIS, PHE‐ARG, and TRP‐ARG pairs exhibited a preferential geometry. The motif pair HIS‐HIS was the most prevalent, accounting for 19.87% of the total, closely followed by TYR‐LYS at 10.17%. Conversely, the motif pair TRP‐HIS had the lowest occurrence, representing only 4.20% of the total. The data generated help in revealing the characteristics and biological functions of cation‐aromatic interactions in biological molecules. The updated version of CAD (Cation‐Aromatic Database V2.0) can be accessed at https://acds.neist.res.in/cadv2. [ABSTRACT FROM AUTHOR]

Mithil Gandhi, co-founder of the AgriTech platform Bael, was in a dilemma. Gandhi was keen on using blockchain as a core technology for Bael to attract investor funds. His plan of action was to implement blockchain technology that offered a secure, transparent and trustworthy platform for the agri-transactions. However, there were challenges in scaling and attracting the stakeholders to adopt the technology, alignment issues with Bael's business model, and his own lack of expertise in blockchain. The case also explores Gandhi's escalation of commitment and how it affects decision making and business alignment. [ABSTRACT FROM AUTHOR]