Synthesis and antibacterial activity of nanoenhanced conjugate of Ag-doped ZnO nanorods with graphene oxide.

In this paper, we report a successful synthesis of ZnO nanorods using the microwave-assisted technique, solid-state reaction method was utilized for the preparation of Zn1-xAgxO (x = 0.05, 0.1), Hummer's modified method for graphene oxide (GO) along with the sonication method to prepare GO-based Ag-doped ZnO (Zn1-xAgxO/GO: x  = 0.05, 0.1) nanocomposites. These nanorods and nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FTIR), high-resolution transmission electron microscopy (HRTEM), and Raman spectroscopy for structural properties, scanning electron microscopy (SEM) along with energy dispersive X-ray (EDX) spectroscopy for morphological analysis, and UV-Vis spectroscopy for optical properties. XRD, FTIR, and Raman measurements substantiated that each sample is well crystallized in the single-phase polycrystalline wurtzite hexagonal structure of ZnO. The average crystallite size is found to be in decreasing order ranges 40 nm to 29 nm, respectively, along with a significant reduction in the optical bandgap. The SEM images showed a clear evidence of nanorods of ZnO, while the EDX spectra verified the presence of Zn, Ag, O, and C elements in the synthesized samples with their nominal percentage. Furthermore, the prepared nanocomposites effectively inhibited the growth ofStaphylococcus aureus and Escherichia coli. In comparison to pure ZnO nanorods, GO-based Ag-doped ZnO nanorods showed improved antibacterial activity against both S. aureus and E. coli.

The Underlying Mechanism of Modulation of Transient Receptor Potential Melastatin 3 by protons.

Transient receptor potential melastatin 3 channel (TRPM3) is a calcium-permeable nonselective cation channel that plays an important role in modulating glucose homeostasis in the pancreatic beta cells. However, how TRPM3 is regulated under physiological and pathological conditions is poorly understood. In this study, we found that both intracellular and extracellular protons block TRPM3 through its binding sites in the pore region. We demonstrated that external protons block TRPM3 with an inhibitory pH50 of 5.5. whereas internal protons inhibit TRPM3 with an inhibitory pH50 of 6.9. We identified three titratable residues, D1059, D1062, and D1073, at the vestibule of the channel pore that contributes to pH sensitivity. The mutation of D1073Q reduced TRPM3 current by low external pH 5.5 from 62 ± 3% in wildtype to 25 ± 6.0% in D1073Q mutant. These results indicate that D1073 is essential for pH sensitivity. In addition, we found that a single mutation of D1059 or D1062 enhanced pH sensitivity. In summary, our findings identify molecular determinants respionsible for the pH regulation of TRPM3. The inhibition of TRPM3 by protons may indicate an endogenous mechanism governing TRPM3 gating and its physiological/pathological functions.

Transient acidosis while retrieving a fear-related memory enhances its lability.

Attenuating the strength of fearful memories could benefit people disabled by memories of past trauma. Pavlovian conditioning experiments indicate that a retrieval cue can return a conditioned aversive memory to a labile state. However, means to enhance retrieval and render a memory more labile are unknown. We hypothesized that augmenting synaptic signaling during retrieval would increase memory lability. To enhance synaptic transmission, mice inhaled CO2 to induce an acidosis and activate acid sensing ion channels. Transient acidification increased the retrieval-induced lability of an aversive memory. The labile memory could then be weakened by an extinction protocol or strengthened by reconditioning. Coupling CO2 inhalation to retrieval increased activation of amygdala neurons bearing the memory trace and increased the synaptic exchange from Ca2+-impermeable to Ca2+-permeable AMPA receptors. The results suggest that transient acidosis during retrieval renders the memory of an aversive event more labile and suggest a strategy to modify debilitating memories.

Vascular Endothelial Primary Cilia: Mechanosensation and Hypertension.

Primary cilia are sensory organelles that extend from the cell surface and sense extracellular signals. Endothelial primary cilia protruding from the inner surface of blood vessel walls sense changes in blood flow and convert this mechanosensation into an intracellular biochemical/molecular signal, which triggers a cellular response. Primary endothelial cilia dysfunction may contribute to the impairment of this response and thus be directly implicated in the development of vascular abnormalities such as hypertension and aneurysms. Using both in vitro techniques as well as in vivo animal models, we and others have investigated fluid flow mechanosensory functions of endothelial cilia in cultured cells, animal models and autosomal dominant polycystic kidney disease (ADPKD) patients. More in-depth studies directed at identification of the mechanisms of fluid flow sensing will further enhance our knowledge of cilia-dependent vascular pathology. Although the current treatments aimed at treating the cardiovascular symptoms in ADPKD patients successfully slowed the progression of cyst growth, there is growing evidence which suggests that drugs which interfere with primary cilia function or structure could reduce cardiovascular complications in ADPKD. This review is to summarize the most recent studies on primary endothelial cilia function in the vascular system and to present primary cilia as a novel therapeutic target for vascular hypertension.