Interactions Required for Binding of Simian Virus 40 T Antigen to the Viral Origin and Molecular Modeling of Initial Assembly Events

The purified T-antigen origin binding domain binds site specifically to site II, the central region of the simian virus 40 core origin. However, in the context of full-length T antigen, the origin binding domain interacts poorly with DNA molecules containing just site II. Here we investigate the contributions of additional core origin regions, termed the flanking sequences, to origin recognition and the assembly of T-antigen hexamers and double hexamers. Results from these studies indicate that in addition to site-specific binding of the T-antigen origin binding domain to site II, T-antigen assembly requires non-sequence-specific interactions between a basic finger in the helicase domain and particular flanking sequences. Related studies demonstrate that the assembly of individual hexamers is coupled to the distortions in the proximal flanking sequence. In addition, the point in the double-hexamer assembly process that is regulated by phosphorylation of threonine 124, the sole posttranslational modification required for initiation of DNA replication, was further analyzed. Finally, T-antigen structural information is used to model various stages of T-antigen assembly on the core origin and the regulation of this process

The Inflammatory Chemokine CXCL10 Modulates Synaptic Plasticity and Neuronal Activity in the Hippocampus

Chemokines, a family member of cytokines, have been shown to play a major role in central nervous system inflammation. Among other chemokines, CXCR3 and its ligand CXCL10 are involved in the pathophysiology of several neuroinflammatory conditions. Most of these conditions are also associated with an increased incidence of seizure or epilepsy. Using age-matched wild-type (WT), as well as CXCR3-receptor-deficient (CXCR3-KO) mice, the present study aimed to investigate the effect of the chemokine CXCL10 and its receptor CXCR3 on synaptic plasticity as well as neuronal activities in hippocampal brain slices. Using field potential and intracellular recordings, the effect of exogenous CXCL10 on tetanus-induced long-term potentiation (LTP) as well as the neuronal spike activity was evaluated in hippocampal CA1 area. Exogenous application of CXCL10 enhanced LTP in WT mice, whereas it exerted no significant effect on CXCR3-KO mice. During intracellular recordings of spontaneous spike activity, exogenous application of CXCL10 significantly enhanced the amplitude, duration, and after-hyperpolarization of action potentials in slices obtained from WT mice compared to CXCR3-KO mice. In addition, CXCR3-KO mice exhibited a lower GABA A -mediated excitation in hippocampal CA1 neurons compared to WT mice. These data show that the inflammatory chemokine CXCL10, probably via its receptor CXCR3, modulates neuronal activity and synaptic plasticity in the hippocampus. CXCL10 may be involved in seizures observed during neuroinflammatory diseases such as meningitis and encephalitis

A novel approach for the biosynthesis of silver nanoparticles using the defensive gland extracts of the beetle, Luprops tristis Fabricius

Abstract Discovering novel natural resources for the biological synthesis of metal nanoparticles is one of the two key challenges facing by the field of nanoparticle synthesis. The second challenge is a lack of information on the chemical components needed for the biological synthesis and the chemical mechanism involved in the metal nanoparticles synthesis. In the current study, microwave-assisted silver nanoparticle (AgNP) synthesis employing the defensive gland extract of Mupli beetle, Luprops tristis Fabricius (Order: Coleoptera; Family: Tenebrionidae), addresses these two challenges. This study was conducted without killing the experimental insect. Earlier studies in our laboratory showed the presence of the phenolic compounds, 2,3-dimethyl-1,4-benzoquinone, 1,3-dihydroxy-2-methylbenzene, and 2,5-dimethylhydroquinone in the defensive gland extract of L. tristis. The results of the current study show that the phenolic compounds in the defensive gland extract of the beetle has the ability to reduce silver ions into AgNPs and also acts as a good capping and stabilizing agent. A possible mechanism for the reduction of silver nitrate (AgNO3) into AgNPs is suggested. The synthesized AgNPs were characterized by Ultraviolet–Visible (UV–Vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy energy-dispersive X-ray (SEM–EDX) analysis and high-resolution transmission electron microscopic (HR-TEM) techniques. The stability of biologically synthesized nanoparticles was studied by zeta potential analysis. The TEM analysis confirmed that AgNPs are well dispersed and almost round shaped. The average size of nanoparticle ranges from 10 to 20 nm. EDX analysis showed that silver is the prominent metal present in the nanomaterial solution. The AgNPs synthesized have antibacterial property against both Staphylococcus aureus and Escherichia coli. Radical scavenging (DPPH) assay was used to determine the antioxidant activity of the AgNPs. AgNPs exhibited anticancer activity in a cytotoxicity experiment against Dalton’s lymphoma ascites (DLA) cell line