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1.
J Neuroinflammation ; 21(1): 38, 2024 Feb 01.
Article En | MEDLINE | ID: mdl-38302975

BACKGROUND: Herpes simplex virus (HSV) encephalitis (HSE) is a serious and potentially life-threatening disease, affecting both adults and newborns. Progress in understanding the virus and host factors involved in neonatal HSE has been hampered by the limitations of current brain models that do not fully recapitulate the tissue structure and cell composition of the developing human brain in health and disease. Here, we developed a human fetal organotypic brain slice culture (hfOBSC) model and determined its value in mimicking the HSE neuropathology in vitro. METHODS: Cell viability and tissues integrity were determined by lactate dehydrogenase release in supernatant and immunohistological (IHC) analyses. Brain slices were infected with green fluorescent protein (GFP-) expressing HSV-1 and HSV-2. Virus replication and spread were determined by confocal microscopy, PCR and virus culture. Expression of pro-inflammatory cytokines and chemokines were detected by PCR. Cell tropism and HSV-induced neuropathology were determined by IHC analysis. Finally, the in situ data of HSV-infected hfOBSC were compared to the neuropathology detected in human HSE brain sections. RESULTS: Slicing and serum-free culture conditions were optimized to maintain the viability and tissue architecture of ex vivo human fetal brain slices for at least 14 days at 37 °C in a CO2 incubator. The hfOBSC supported productive HSV-1 and HSV-2 infection, involving predominantly infection of neurons and astrocytes, leading to expression of pro-inflammatory cytokines and chemokines. Both viruses induced programmed cell death-especially necroptosis-in infected brain slices at later time points after infection. The virus spread, cell tropism and role of programmed cell death in HSV-induced cell death resembled the neuropathology of HSE. CONCLUSIONS: We developed a novel human brain culture model in which the viability of the major brain-resident cells-including neurons, microglia, astrocytes and oligodendrocytes-and the tissue architecture is maintained for at least 2 weeks in vitro under serum-free culture conditions. The close resemblance of cell tropism, spread and neurovirulence of HSV-1 and HSV-2 in the hfOBSC model with the neuropathological features of human HSE cases underscores its potential to detail the pathophysiology of other neurotropic viruses and as preclinical model to test novel therapeutic interventions.


Encephalitis, Herpes Simplex , Herpes Simplex , Herpesvirus 1, Human , Infant, Newborn , Adult , Humans , Astrocytes/pathology , Necroptosis , Herpes Simplex/pathology , Brain/pathology , Cytokines , Neurons/pathology , Chemokines
2.
bioRxiv ; 2023 Oct 09.
Article En | MEDLINE | ID: mdl-37873286

When interacting with their environment, animals must balance exploratory and defensive behavior to evaluate and respond to potential threats. The lateral septum (LS) is a structure in the ventral forebrain that calibrates the magnitude of behavioral responses to stress-related external stimuli, including the regulation of threat avoidance. The complex connectivity between the LS and other parts of the brain, together with its largely unexplored neuronal diversity, makes it difficult to understand how defined LS circuits control specific behaviors. Here, we describe a mouse model in which a population of neurons with a common developmental origin (Nkx2.1-lineage neurons) are absent from the LS. Using a combination of circuit tracing and behavioral analyses, we found that these neurons receive inputs from the perifornical area of the anterior hypothalamus (PeFAH) and are specifically activated in stressful contexts. Mice lacking Nkx2.1-lineage LS neurons display increased exploratory behavior even under stressful conditions. Our study extends the current knowledge about how defined neuronal populations within the LS can evaluate contextual information to select appropriate behavioral responses. This is a necessary step towards understanding the crucial role that the LS plays in neuropsychiatric conditions where defensive behavior is dysregulated, such as anxiety and aggression disorders.

4.
Brain Pathol ; 32(4): e13044, 2022 07.
Article En | MEDLINE | ID: mdl-34913212

Increasing evidence supports the role of neurotropic herpes simplex virus 1 (HSV-1) in the pathogenesis of Alzheimer's disease (AD). However, it is unclear whether previously reported findings in HSV-1 cell culture and animal models can be translated to humans. Here, we analyzed clinical specimens from latently HSV-1 infected individuals and individuals with lytic HSV infection of the brain (herpes simplex encephalitis; HSE). Latent HSV-1 DNA load and latency-associated transcript (LAT) expression were identical between trigeminal ganglia (TG) of AD patients and controls. Amyloid ß (Aß) and hyperphosphorylated tau (pTau) were not detected in latently HSV-infected TG neurons. Aging-related intraneuronal Aß accumulations, neurofibrillary tangles (NFT), and/or extracellular Aß plaques were observed in the brain of some HSE patients, but these were neither restricted to HSV-infected neurons nor brain regions containing virus-infected cells. Analysis of unique brain material from an AD patient with concurrent HSE showed that HSV-infected cells frequently localized close to Aß plaques and NFT, but were not associated with exacerbated AD-related pathology. HSE-associated neuroinflammation was not associated with specific Aß or pTau phenotypes. Collectively, we observed that neither latent nor lytic HSV infection of human neurons is directly associated with aberrant Aß or pTau protein expression in ganglia and brain.


Alzheimer Disease , Amyloid beta-Peptides/metabolism , Herpes Simplex , Herpesvirus 1, Human , tau Proteins/metabolism , Animals , Brain/metabolism , Herpes Simplex/metabolism , Herpesvirus 1, Human/metabolism , Humans , Neurons/metabolism , Plaque, Amyloid , Trigeminal Ganglion/metabolism
5.
Viruses ; 13(8)2021 08 10.
Article En | MEDLINE | ID: mdl-34452447

Measles virus (MV) and canine distemper virus (CDV) are closely related members of the family Paramyxoviridae, genus Morbillivirus. MV infection of humans and non-human primates (NHPs) results in a self-limiting disease, which rarely involves central nervous system (CNS) complications. In contrast, infection of carnivores with CDV usually results in severe disease, in which CNS complications are common and the case-fatality rate is high. To compare the neurovirulence and neurotropism of MV and CDV, we established a short-term organotypic brain slice culture system of the olfactory bulb, hippocampus, or cortex obtained from NHPs, dogs, and ferrets. Slices were inoculated ex vivo with wild-type-based recombinant CDV or MV expressing a fluorescent reporter protein. The infection level of both morbilliviruses was determined at different times post-infection. We observed equivalent infection levels and identified microglia as main target cells in CDV-inoculated carnivore and MV-inoculated NHP brain tissue slices. Neurons were also susceptible to MV infection in NHP brain slice cultures. Our findings suggest that MV and CDV have comparable neurotropism and intrinsic capacity to infect CNS-resident cells of their natural host species.


Brain/virology , Distemper Virus, Canine/physiology , Measles virus/physiology , Viral Tropism , Animals , Brain/cytology , Distemper/virology , Distemper Virus, Canine/pathogenicity , Dogs , Ferrets , Host Specificity , Humans , Measles/virology , Microglia/virology , Neurons/virology , Organ Culture Techniques , Primates
6.
Nanotechnology ; 32(40)2021 Jul 13.
Article En | MEDLINE | ID: mdl-34102628

Owing to many fascinating properties including high thermal and chemical stability, excellent electrical insulation, fire-retardant and antibacterial properties, hexagonal boron nitride (hBN) has emerged as a prominent 2D material for broad applications. However, the production of high quality of hBN by chemical exfoliation from its precursor is still challenging. This paper presents a high-yield (+83%), low-cost and energy-efficient wet chemical exfoliation strategy, which produces few-layers (FL, 3-6 layers) of edge-functionalized (OH) hBN nanosheets with uniform size (486 ± 51 nm). This optimized preparation is established based on a comprehensive investigation on the key exfoliation parameters such as exfoliation temperature, time and amount of the oxidant (potassium permanganate). High quality of FL-hBN was confirmed by various characterization techniques including scanning electron microscopy coupled with energy dispersive X-ray, transmission electron microscopy, Raman, Fourier transform infrared spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy analyses. The outcome of this study paves a promising pathway to effectively produce hBN through a cost-efficient exfoliation approach, which has a significant impact on industrial applications.

7.
J Clin Invest ; 131(1)2021 01 04.
Article En | MEDLINE | ID: mdl-32990676

Protection of the brain from viral infections involves the type I IFN (IFN-I) system, defects in which render humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels lead to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we showed that microglia and other immune cells undergo apoptosis in the HSV-1-infected brain through a mechanism dependent on the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, whereas lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1-infected organotypic brain slices or mice treated with a caspase inhibitor exhibited lower viral load and an improved infection outcome. Collectively, we identify an activation-induced apoptosis program in brain immune cells that downmodulates local immune responses.


Brain/immunology , Herpes Simplex/immunology , Herpesvirus 1, Human/immunology , Interferon Type I/immunology , Membrane Proteins/immunology , Nucleotidyltransferases/immunology , Animals , Apoptosis/genetics , Apoptosis/immunology , Brain/virology , Herpes Simplex/genetics , Humans , Interferon Type I/genetics , Male , Membrane Proteins/genetics , Mice , Mice, Knockout , Microglia/immunology , Microglia/virology , Nucleotidyltransferases/genetics
8.
Development ; 147(22)2020 11 16.
Article En | MEDLINE | ID: mdl-33060132

The mammalian cortex is populated by neurons derived from neural progenitors located throughout the embryonic telencephalon. Excitatory neurons are derived from the dorsal telencephalon, whereas inhibitory interneurons are generated in its ventral portion. The transcriptional regulator PRDM16 is expressed by radial glia, neural progenitors present in both regions; however, its mechanisms of action are still not fully understood. It is unclear whether PRDM16 plays a similar role in neurogenesis in both dorsal and ventral progenitor lineages and, if so, whether it regulates common or unique networks of genes. Here, we show that Prdm16 expression in mouse medial ganglionic eminence (MGE) progenitors is required for maintaining their proliferative capacity and for the production of proper numbers of forebrain GABAergic interneurons. PRDM16 binds to cis-regulatory elements and represses the expression of region-specific neuronal differentiation genes, thereby controlling the timing of neuronal maturation. PRDM16 regulates convergent developmental gene expression programs in the cortex and MGE, which utilize both common and region-specific sets of genes to control the proliferative capacity of neural progenitors, ensuring the generation of correct numbers of cortical neurons.


Cerebral Cortex/metabolism , DNA-Binding Proteins/metabolism , GABAergic Neurons/metabolism , Interneurons/metabolism , Neural Stem Cells/metabolism , Transcription Factors/metabolism , Animals , Cerebral Cortex/cytology , DNA-Binding Proteins/genetics , GABAergic Neurons/cytology , Interneurons/cytology , Mice , Neural Stem Cells/cytology , Transcription Factors/genetics
9.
ACS Omega ; 4(22): 19787-19798, 2019 Nov 26.
Article En | MEDLINE | ID: mdl-31788611

The synthesis of graphene materials with multiple surface chemistries and functionalities is critical for further improving their properties and broadening their emerging applications. We present a simple chemical approach to obtain bulk quantities of multifunctionalized reduced graphene oxide (rGO) that combines chemical doping and functionalization using the thiol-ene click reaction. Controllable modulation of chemical multifunctionality was achieved by simultaneous nitrogen doping and gradual chemical reduction of graphene oxide (GO) using ammonia and hydrazine, followed by covalent attachment of amino-terminated thiol molecules using the thiol-ene click reaction. A series of N-doped rGO (N-rGO) precursors with different levels of oxygen groups were synthesized by adjusting the amount of reducing agent (hydrazine), followed by subsequent covalent attachment of cysteamine via the thermal thiol-ene click reaction to yield different ratios of mixed functional groups including N (pyrrolic N, graphitic N, and aminic N), S (thioether S, thiophene S, and S oxides), and O (hydroxyl O, carbonyl O, and carboxyl O) on the reduced GO surface. Detailed XPS analysis confirmed the disappearance of unstable pyridinic N in cys-N-rGO and the reduction degree threshold of N-rGO for effective cysteamine modification to take place. Our study establishes a strong correlation between different reduction degrees of N-rGO with several existing oxygen functional groups and addition of new tunable functionalities including covalently attached nitrogen (amino) and sulfur (C-S-C, C=S, and S-O). This simple and versatile approach provides a valuable contribution for practical designing and synthesis of a broad range of functionalized graphene materials with tailorable functionalities, doping levels, and interfacial properties for potential applications such as polymer composites, supercapacitors, electrocatalysis, adsorption, and sensors.

10.
ACS Appl Mater Interfaces ; 11(6): 6350-6362, 2019 Feb 13.
Article En | MEDLINE | ID: mdl-30507147

Engineering of multifunctional binding chemistry on graphene composites using thiol-ene click reaction for selective and highly efficient adsorption of mercury(II) is demonstrated. Graphene oxide (GO) is used as an initial material for covalent attachment of cysteamine molecules by thiol-ene click reaction on C═C groups to achieve a partially reduced graphene surface with multiple binding chemistry such as O, S, and N. Batch adsorption studies showed remarkable adsorption rate with only 1 mg L-1 dosage of adsorbent used to remove 95% Hg (II) (∼1.5 mg L-1) within 90 min. The high adsorption capacity of 169 ± 19 mg g-1, high selectivity toward Hg in the presence of 30 times higher concentration of competing ions (Cd, Cu, Pb) and high regeneration ability (>97%) for five consecutive adsorption-desorption cycles were achieved. Comparative study with commercial activated carbon using spiked Hg (II) river water confirmed the high performance and potential of this adsorbent for real mercury remediation of environmental and drinking waters.

11.
J Colloid Interface Sci ; 539: 315-325, 2019 Mar 15.
Article En | MEDLINE | ID: mdl-30594006

We report a synthesis of magnetic nanoparticles chemically immobilized onto reduced graphene oxide sheets (referred to as rGO-Fe3O4 NPs) as a gas and vapor sensing platform with precisely designed particle size of 5, 10 and 20 nm to explore their influence of particle size on sensing performance. The rGO-Fe3O4 NP sensors have been investigated their responses to different gases and volatile organic compounds (VOCs) at part-per-million (ppm) levels. Results show that the Fe3O4 NPs with smaller size (5 and 10 nm) on the rGO surface led to a lower sensitivity, while particles of a size of 20 nm have a significant enhancement of sensitivity compared to the bare rGO sensor. The rGO-Fe3O4 NP20 sensor can detect trace amounts of NO2 gas and ethanol vapor at the 1 ppm and is highly selective to the NO2 and ethanol among other tested gases and VOCs, respectively. The particle size causes different distribution behaviour of NPs over rGO surface and interspaced between them, which results in deceased or increased the surface interactions between gas and graphene. The NPs themselves contained different defects level and the charge depletion layer that affect their adsorption gas/vapor molecules, which are explained for different sensing responses.

12.
RSC Adv ; 8(61): 34848-34852, 2018 Oct 10.
Article En | MEDLINE | ID: mdl-35547056

Iron oxides and their hydroxides have been studied and analysed with properties of their mutual transformations under different hydrothermal conditions being indicated. Amorphous bacteria nanowires produced from biofilm waste were investigated under the influence of pH at a fixed duration (20 h) and reaction temperature (200 °C). The morphology, structure, and particle size of the transformation of hematite (α-Fe2O3) was obtained and characterised with SEM, XRD, FTIR, and particle sizer. The optimal conditions for the complete conversion of amorphous iron oxide nanowires to crystalline α-Fe2O3 is under acidic conditions where the pH is 1. The flower-like α-Fe2O3 structures have photocatalytic activity and adsorbent properties for heavy metal ions. This one-pot synthesis approach to produce α-Fe2O3 at a low cost would be greatly applicable to the recycling process of biofilm waste in order to benefit the environment.

13.
ACS Appl Mater Interfaces ; 9(49): 43275-43286, 2017 Dec 13.
Article En | MEDLINE | ID: mdl-29165994

Graphene materials have been extensively explored and successfully used to improve performances of cement composites. These formulations were mainly optimized based on different dosages of graphene additives, but with lack of understanding of how other parameters such as surface chemistry, size, charge, and defects of graphene structures could impact the physiochemical and mechanical properties of the final material. This paper presents the first experimental study to evaluate the influence of oxygen functional groups of graphene and defectiveness of graphene structures on the axial tension and compression properties of graphene-cement mortar composites. A series of reduced graphene oxide (rGO) samples with different levels of oxygen groups (high, mild, and low) were prepared by the reduction of graphene oxide (GO) using different concentrations of hydrazine (wt %, 0.1, 0.15, 0.2, 0.3, and 0.4%) and different reduction times (5, 10, 15, 30, and 60 min) and were added to cement mortar composites at an optimal dosage of 0.1%. A series of characterization methods including scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, thermogravimetric analysis, and Fourier transform infrared spectroscopy were performed to determine the distribution and mixing of the prepared rGO in the cement matrix and were correlated with the observed mechanical properties of rGO-cement mortar composites. The measurement of the axial tension and compression properties revealed that the oxygen level of rGO additives has a significant influence on the mechanical properties of cement composites. An addition of 0.1% rGO prepared by 15 min reduction and 0.2% (wt %) hydrazine with mild level of oxygen groups resulted in a maximum enhancement of 45.0 and 83.7%, respectively, in the 28-day tensile and compressive strengths in comparison with the plain cement mortar and were higher compared to the composite prepared with GO (37.5 and 77.7%, respectively). These results indicate that there is a strong influence of the level of oxygen groups and crystallinity of graphene structures on the physiochemical and mechanical properties. The influence of these two parameters are interconnected and their careful balancing is required to provide an optimum level of oxygen groups on rGO sheets to ensure that there is sufficient bonding between the calcium silicate hydrate (C-S-H) components in the cement matrix and minimum level of defects and higher crystallinity of graphene structures, which will improve the mechanical properties of the composite. Finding the optimized balance between these two parameters is required to formulate graphene cement composites with the highest performance.

14.
ACS Appl Mater Interfaces ; 9(49): 43325-43335, 2017 Dec 13.
Article En | MEDLINE | ID: mdl-29160685

The environmental problems and low efficiency associated with conventional fertilizers provides an impetus to develop advanced fertilizers with slower release and better performances. Here, we report of development of a new carrier platform based on graphene oxide (GO) sheets that can provide a high loading of plant micronutrients with controllable slow release. To prove this concept, two micronutrients, zinc (Zn) and copper (Cu), were used to load on GO sheets and hence formulate GO-based micronutrients fertilizer. The chemical composition and successful loading of both nutrients on GO sheets were confirmed by X-ray photoelectron spectroscopy, thermogravimetric analysis, and X-ray diffraction (XRD). The prepared Zn-graphene oxide (Zn-GO) and Cu-graphene oxide (Cu-GO) fertilizers showed a biphasic dissolution behavior compared to that of commercial zinc sulfate and copper sulfate fertilizer granules, displaying desirable fast and slow micronutrient release. A visualization method and chemical analysis were used to assess the release and diffusion of Cu and Zn in soil from GO-based fertilizers compared with commercial soluble fertilizers to demonstrate the advantages of GO carriers and show their capability to be used as a generic platform for macro- and micronutrients delivery. A pot trial demonstrated that Zn and Cu uptake by wheat was higher when using GO-based fertilizers compared to that when using standard zinc or copper salts. This is the first report on the agronomic performance of GO-based slow-release fertilizer.


Micronutrients/chemistry , Fertilizers , Graphite , Soil , Zinc
15.
ACS Appl Mater Interfaces ; 9(11): 10160-10168, 2017 Mar 22.
Article En | MEDLINE | ID: mdl-28244736

To address high fire risks of flamable cellulosic materials, that can trigger easy combustion, flame propagation, and release of toxic gases, we report a new fire-retardant approach using synergetic actions combining unique properties of reduced graphene oxide (rGO) and hydrated-sodium metaborates (SMB). The single-step treatment of cellulosic materials by a composite suspension of rGO/SMB was developed to create a barrier layer on sawdust surface providing highly effective fire retardant protection with multiple modes of action. These performances are designed considering synergy between properties of hydrated-SMB crystals working as chemical heat-sink to slow down the thermal degradation of the cellulosic particles and gas impermeable rGO layers that prevents access of oxygen and the release of toxic volatiles. The rGO outer layer also creates a thermal and physical barrier by donating carbon between the flame and unburnt wood particles. The fire-retardant performance of developed graphene-borate composite and mechanism of fire protection are demonstrated by testing of different forms of cellulosic materials such as pine sawdust, particle-board, and fiber-based structures. Results revealed their outstanding self-extinguishing behavior with significant resistance to release of toxic and flammable volatiles suggesting rGO/SMB to be suitable alternative to the conventional toxic halogenated flame-retardant materials.

16.
ACS Appl Mater Interfaces ; 9(9): 8393-8402, 2017 Mar 08.
Article En | MEDLINE | ID: mdl-28192650

Adhesion behavior of superhydrophobic (SH) surfaces is an active research field related to various engineering applications in controlled microdroplet transportation, self-cleaning, deicing, biochemical separation, tissue engineering, and water harvesting. Herein, we report a facile approach to control droplet adhesion, bouncing and rolling on properties of SH surfaces by tuning their air-gap and roughness-height by altering the concentrations of poly dimethyl-siloxane (PDMS). The optimal use of PDMS (4-16 wt %) in a dual-scale (nano- and microparticles) composite enables control of the specific surface area (SSA), pore volume, and roughness of matrices that result in a well-controlled adhesion between water droplets and SH surfaces. The sliding angles of these surfaces were tuned to be varied between 2 ± 1 and 87 ± 2°, which are attributed to the transformation of the contact type between droplet and surface from "point contact" to "area contact". We further explored the effectiveness of these low and high adhesive SH surfaces in icing and deicing actions, which provides a new insight into design highly efficient and low-cost ice-release surface for cold temperature applications. Low adhesion (lotus effect) surface with higher pore-volume exhibited relatively excellent ice-release properties with significant icing delay ability principally attributed to the large air gap in the coating matrix than SH matrix with high adhesion (petal effect).

17.
ACS Appl Mater Interfaces ; 8(25): 16521-32, 2016 Jun 29.
Article En | MEDLINE | ID: mdl-27268515

Here, we report a new method to prepare graphene from graphite by the liquid phase exfoliation process with sonication using graphene oxide (GO) as a dispersant. It was found that GO nanosheets act a as surfactant to the mediated exfoliation of graphite into a GO-adsorbed graphene complex in the aqueous solution, from which graphene was separated by an additional process. The preparation of isolated graphene from a single to a few layers is routinely achieved with an exfoliation yield of up to higher than 40% from the initial graphite material. The prepared graphene sheets showed a high quality (C/O ∼ 21.5), low defect (ID/IG ∼ 0.12), and high conductivity (6.2 × 10(4) S/m). Moreover, the large lateral size ranging from 5 to 10 µm of graphene, which is believed to be due to the shielding effect of GO avoiding damage under ultrasonic jets and cavitation formed by the sonication process. The thin graphene film prepared by the spray-coating technique showed a sheet resistance of 668 Ω/sq with a transmittance of 80% at 550 nm after annealing at 350 °C for 3 h. The transparent electrode was even greater with the resistance only 66.02 Ω when graphene is deposited on an interdigitated electrode (1 mm gap). Finally, a flexible sensor based on a graphene spray-coating polydimethylsiloxane (PDMS) is demonstrated showing excellent performance working under human touch pressure (<10 kPa). The graphene prepared by this method has some distinct properties showing it as a promising material for applications in electronics including thin film coatings, transparent electrodes, wearable electronics, human monitoring sensors, and RFID tags.

18.
Am J Pathol ; 186(6): 1623-34, 2016 06.
Article En | MEDLINE | ID: mdl-27106764

Valosin-containing protein (VCP) mutations cause inclusion body myopathy with Paget disease and frontotemporal dementia. However, the mechanisms by which mutant VCP triggers degeneration remain unknown. Here, we investigated the role of VCP in cellular stress and found that the oxidative stressor arsenite and heat shock-activated stress responses evident by T-intracellular antigen-1-positive granules in C2C12 myoblasts. Granules also contained phosphorylated transactive response DNA-binding protein 43, ubiquitin, microtubule-associated protein 1A/1B light chains 3, and lysosome-associated membrane protein 2. Mutant VCP produced more T-intracellular antigen-1-positive granules than wild-type in the postarsenite exposure period. Similar results were observed for other granule components, indicating that mutant VCP delayed clearance of stress granules. Furthermore, stress granule resolution was impaired on differentiated C2C12 cells expressing mutant VCP. To address whether mutant VCP triggers dysregulation of the stress granule pathway in vivo, we analyzed skeletal muscle of aged VCPR155H-knockin mice. We found significant increments in oxidated proteins but observed the stress granule markers RasGAP SH3-binding protein and phosphorylated eukaryotic translation initiation factor 2α unchanged. The mixed results indicate that mutant VCP together with aging lead to higher oxidative stress in skeletal muscle but were insufficient to disrupt the stress granule pathway. Our findings support that deficiencies in recovery from stressors may result in attenuated tolerance to stress that could trigger muscle degeneration.


Adenosine Triphosphatases/genetics , Cell Cycle Proteins/genetics , Frontotemporal Dementia/pathology , Muscular Dystrophies, Limb-Girdle/pathology , Myoblasts/pathology , Myositis, Inclusion Body/pathology , Osteitis Deformans/pathology , Oxidative Stress/physiology , Animals , Cell Line , Disease Models, Animal , Fluorescent Antibody Technique , Frontotemporal Dementia/genetics , Humans , Immunoblotting , Immunohistochemistry , Mice , Muscular Dystrophies, Limb-Girdle/genetics , Myoblasts/metabolism , Myositis, Inclusion Body/genetics , Osteitis Deformans/genetics , Transfection , Valosin Containing Protein
19.
ACS Appl Mater Interfaces ; 7(51): 28482-93, 2015 Dec 30.
Article En | MEDLINE | ID: mdl-26632960

Superhydrophobic surfaces for self-cleaning applications often suffer from mechanical instability and do not function well after abrasion/scratching. To address this problem, we present a method to prepare graphene-based superhydrophobic composite coatings with robust mechanical strength, self-cleaning, and barrier properties. A suspension has been formulated that contains a mixture of reduced graphene oxide (rGO) and diatomaceous earth (DE) modified with polydimethylsiloxane (PDMS) that can be applied on any surface using common coating methods such as spraying, brush painting, and dip coating. Inclusion of TiO2 nanoparticles to the formulation shows further increase in water contact angle (WCA) from 159 ± 2° to 170 ± 2° due to the structural improvement with hierarchical surface roughness. Mechanical stability and durability of the coatings has been achieved by using a commercial adhesive to bond the superhydrophobic "paint" to various substrates. Excellent retention of superhydrophobicity was observed even after sandpaper abrasion and crosscut scratching. A potentiodynamic polarization study revealed excellent corrosion resistance (96.78%) properties, and an acid was used to provide further insight into coating barrier properties. The ease of application and remarkable properties of this graphene-based composite coating show considerable potential for broad application as a self-cleaning and protective layer.

20.
ACS Appl Mater Interfaces ; 7(18): 9758-66, 2015 May 13.
Article En | MEDLINE | ID: mdl-25871444

Arsenic (As) is the world's most hazardous chemical found in drinking water of many countries; therefore, there is an urgent need for the development of low-cost adsorbents for its removal. Here, we report a highly versatile and synthetic route for the preparation of a three-dimensional (3D) graphene-iron oxide nanoparticle aerogel composite for the efficient removal of As from contaminated water. This unique three-dimensional (3D) interconnected network was prepared from natural graphite rocks with a simple reaction, without the use of harsh chemicals, which combines with the exfoliation of graphene oxide (GO) sheets via the reduction of ferrous ion to form a graphene aerogel composite decorated with iron oxide nanoparticles. The prepared adsorbent showed outstanding absorption performance for the removal of As from contaminated water, because of its high surface-to-volume ratio and characteristic pore network in the 3D architecture. The performed case study using real drinking water contaminated with As under batch conditions showed successful removal of arsenic to the concentration recommended by the World Health Organisation (WHO).

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