compromises integrity of the podocyte actin cytoskeleton through downregulation of the vitamin D receptor.

The HIV-1 accessory protein Nef is considered to play an important role in the development of podocyte phenotype in HIV-1 associated nephropathy. We hypothesized that Nef may be altering podocyte phenotype both structurally and functionally. To elucidate the involved mechanisms, podocyte proteins interacting with Nef were identified using GST pull down assay and yeast two hybrid assay. The GST pull down assay on protein extracts made from stable colonies of conditionally immortalized human podocytes expressing Nef (Nef/CIHP) displayed a band at 45 kD, which was identified as actin by mass spectrometry. Yeast two hybrid assay identified the following Nef-interacting proteins: syntrophin, filamin B, syntaxin, translational elongation factor 1, and zyxin. The Nef-actin and Nef- zyxin interactions were confirmed by co-localization studies on Nef/CIHP stable cell lines. The co-localization studies also showed that Nef/CIHP stable cell lines had decreased number of actin filaments (stress fibers), displayed formation of lamellipodia, and increased number of podocyte projectons (filopodia). Nef/CIHP displayed enhanced cortical F-actin score index (P<0.001) and thus indicating reorganization of F-actin in the cortical regions. Microarray analysis showed that Nef enhanced the expression of Rac1, syndecan-4, Rif, and CDC42 and attenuated the expression of syndecan-3 and syntenin. In addition, Nef/CIHPs displayed diminished sphingomyelinase (ASMase) activity. Functionally, Nef/CIHPs displayed diminished attachment and enhanced detachment to their substrate. These findings indicate that Nef interaction with actin compromises podocyte cytoskeleton integrity.

Engineered nanomaterials (ENM) are being used in a wide range of consumer products and pharmaceuticals; hence, there is an increasing risk for human exposure and potential adverse outcomes. The immune system, vital in host defense and protection against environmental agents, is typically initiated and executed by innate effector immune cells including macrophages and neutrophils. Previous literature has reported the immune system as a major target of ENM toxicity; however, there is inconsistency regarding the immunotoxicity of ENM. This could be attributed to differences in ENM physicochemical properties, cellular models examined, biocorona formation, etc. Thus, the current study examined the toxicity and immunomodulatory effects of silver nanoparticles (AgNP), one of the most utilized ENM in consumer and medical products, in two key innate immune cell models, e.g. RAW 264.7 cells (macrophages) and differentiated MPRO 2.1 cells (promyelocytes/neutrophils). The results showed that despite a generation of reactive oxygen species, exposure to 20 nm citrate-coated AgNP was not associated with major oxidative damage, inflammatory responses, nor cytotoxicity. Nevertheless, and most importantly, pre-exposure to the AgNP for 24 h enhanced RAW 264.7 cell phagocytic ability as well as the release of inflammatory cytokine interleukin-6 in response to lipopolysaccharide (LPS). In MPRO 2.1 cells, AgNP pre-exposure also resulted in enhanced phagocytic ability; however, these cells manifest reduced cell degranulation (elastase release) and oxidative burst in response to phorbol myristate acetate (PMA). Taken together, these findings indicated to us that exposure to AgNP, despite not being directly (cyto)toxic to these cells, had the potential to alter immune cell responses. The findings underscore the import of assessing immune cell function post-exposure to ENM beyond the standard endpoints such as oxidative stress and cytotoxicity. In addition, these findings further illustrate the importance of understanding the underlying molecular mechanisms of ENM-cellular interactions, particularly in the immune system.

Opiates have been reported to induce T cell loss. We evaluated the role of vitamin D receptor (VDR) and the activation of the renin-angiotensin system (RAS) in morphine-induced T cell loss. Morphine-treated human T cells displayed downregulation of VDR and the activation of the RAS. On the other hand, a VDR agonist (EB1089) enhanced T cell VDR expression both under basal and morphine-stimulated states. Since T cells with silenced VDR displayed the activation of the RAS, whereas activation of the VDR was associated with downregulation of the RAS, it appears that morphine-induced T cell RAS activation was dependent on the VDR status. Morphine enhanced reactive oxygen species (ROS) generation in a dose-dependent manner. Naltrexone (an opiate receptor antagonist) inhibited morphine-induced ROS generation and thus, suggested the role of opiate receptors in T cell ROS generation. The activation of VDR as well as blockade of ANG II (by losartan, an AT(1) receptor blocker) also inhibited morphine-induced T cell ROS generation. Morphine not only induced double-strand breaks (DSBs) in T cells but also attenuated DNA repair response, whereas activation of VDR not only inhibited morphine-induced DSBs but also enhanced DNA repair. Morphine promoted T cell apoptosis; however, this effect of morphine was inhibited by blockade of opiate receptors, activation of the VDR, and blockade of the RAS. These findings indicate that morphine-induced T cell apoptosis is mediated through ROS generation in response to morphine-induced downregulation of VDR and associated activation of the RAS.

Ethanol has been demonstrated to cause T cell apoptosis. In the present study, we evaluated the role of VDR and the renin angiotensin system (RAS) in oxidative stress-induced T cell apoptosis. Ethanol-treated human T cells displayed down regulation of vitamin D receptor (VDR) and the activation of the RAS in the form of enhanced T cell renin expression and angiotensin II (Ang II) production. The silencing of VDR with siRNA displayed the activation of the RAS, and activation of the VDR resulted in the down regulation of the RAS. It suggested that ethanol-induced T cell RAS activation was dependent on the VDR status. T cell ROS generation by ethanol was found to be dose dependent. Conversely, ethanol-induced ROS generation was inhibited if VDR was activated or Ang II was blocked by an angiotensin II type 1 (AT1) receptor blocker (Losartan). Furthermore, it was observed that ethanol not only induced double strand breaks in T cells but also attenuated DNA repair response, whereas, VDR activation inhibited ethanol-induced double strand breaks and also enhanced DNA repairs. Since free radical scavengers inhibited ethanol-induced DNA damage, it would indicate that ethanol-induced DNA damage was mediated through ROS generation. These findings indicated that ethanol-induced T cell apoptosis was mediated through ROS generation in response to ethanol-induced down regulation of VDR and associated activation of the RAS.

Triboelectric nanogenerators (TENGs) convert mechanical energy, e.g., from human motions, into electrical power. The mechanical force brings two triboelectric materials with different electron affinities into contact, resulting in a voltage that can be used to power a device. Although progress has been made in identifying high‐performance triboelectric materials (e.g., polytetrafluoroethylene, MXenes, polyethylene terephthalate (PET), graphene‐impregnated polymers, and polyimide), the search for better triboelectric materials continues in order to harvest mechanical energy efficiently. Here, it is demonstrated that the output performance of a TENG can be enhanced by coating its triboelectric material surface with an important class of carbons, viz., zero‐dimensional C60 fullerene, which is known for its high electron affinity. Specifically, a C60 fullerene‐based TENG (F‐TENG) is fabricated and evaluated that supports a high open‐circuit voltage of ≈1.6 kV, short‐circuit current of ≈100 µA, instantaneous peak power density of ≈38 W m−2, and charging of a 1 µF capacitor to 180 V under 8 min. Because of the superior power output of the F‐TENG, a digital watch can be powered continuously in real‐time, a task that cannot be performed with a similar‐sized TENG comprising PET and polyimide. Notably, a novel methodology based on the analysis of the TENG output waveforms is presented for determining the triboelectric charge, which can then be used to rank the electrode material in the tribolelectric series.

Amyloid fibrillation is known to contribute in a variety of diseases including neurodegenerative disorders (e.g., Alzheimer's and Parkinson's disease) and type II diabetes. The inhibition of fibrillation has been suggested as a possible therapeutic strategy to prevent neuronal and pancreatic β-cell death associated with amyloid diseases. To this end, strong hydrophobic and π-π interactions between proteins and nanomaterials at the nanobio interface could be used to mitigate the stacking of amyloid structures associated with fibrillation. In this study, the authors show that exfoliated graphene effectively inhibits the formation of amyloid fibrils using a model amyloid-forming protein, viz., hen egg white lysozyme (HEWL). While previous theoretical models posit that hydrophobic and π-π stacking interactions result in strong interactions between graphene and proteins, the authors experimentally identified the presence of additional interfacial charge transfer interactions between HEWL and graphene using micro-Raman spectroscopy and Kelvin probe force microscopy. Their photoluminescence spectroscopy and transmission electron microscopy studies evince that the interfacial charge transfer combined with hydrophobic and π-π stacking interactions, specifically between the nanomaterial and the amino acid tryptophan, increase HEWL adsorption on graphene and thereby inhibit amyloid fibrillation.

In the present study Nano Calcium-Aluminium mixed oxide material (NCAMO) was synthesized by solution combustion method in 1:1, 1:2, 4:1, 3:2 molar ratios of Calcium and Aluminum nitrates as oxidizers and urea as fuel for an efficient adsorption of fluoride from drinking water.Molar composition of 1:1 ratio was found to exhibit better adsorption properties and the same Downloaded by [University of Birmingham] at 02:47 23 March 2015 A c c e p t e d M a n u s c r i p t 2 was characterized by XRD, FESEM, and FTIR. The optimized conditions for maximum adsorption capacity were achieved at pH4 with contact time of 4 hours by adding 1g/L of NCAMO to initial fluoride concentration of 8mg/L. The sorption of fluoride on NCAMO followed Langmuir isotherm model strongly suggested monolayer adsorption. The calculated equilibrium adsorption capacity 23.7 mg/g of NCAMO strongly suggests the dominance of monolayer adsorption process. The adsorption kinetics was well described by pseudo-second order equation confirming chemisorption.