Global Lipidome Profiling Revealed Multifaceted Role of Lipid Species in Hepatitis C Virus Replication, Assembly, and Host Antiviral Response.

Hepatitis C virus (HCV) is a major human pathogen that requires a better understanding of its interaction with host cells. There is a close association of HCV life cycle with host lipid metabolism. Lipid droplets (LDs) have been found to be crucial organelles that support HCV replication and virion assembly. In addition to their role in replication, LDs also have protein-mediated antiviral properties that are activated during HCV infection. Studies have shown that HCV replicates well in cholesterol and sphingolipid-rich membranes, but the ways in which HCV alters host cell lipid dynamics are not yet known. In this study, we performed a kinetic study to check the enrichment of LDs at different time points of HCV infection. Based on the LD enrichment results, we selected early and later time points of HCV infection for global lipidomic study. Early infection represents the window period for HCV sensing and host immune response while later infection represents the establishment of viral RNA replication, virion assembly, and egress. We identified the dynamic profile of lipid species at early and later time points of HCV infection by global lipidomic study using mass spectrometry. At early HCV infection, phosphatidylinositol phospholipids (PIPs), lysophosphatidic acid (LPA), triacyl glycerols (TAG), phosphatidylcholine (PC), and trihexosylceramides (Hex3Cer) were observed to be enriched. Similarly, free fatty acids (FFA), phosphatidylethanolamine (PE), N-acylphosphatidylethanolamines (NAPE), and tri acylglycerols were enriched at later time points of HCV infection. Lipids enriched at early time of infection may have role in HCV sensing, viral attachment, and immune response as LPA and PIPs are important for immune response and viral attachment, respectively. Moreover, lipid species observed at later infection may contribute to HCV replication and virion assembly as PE, FFA, and triacylglycerols are known for the similar function. In conclusion, we identified lipid species that exhibited dynamic profile across early and later time points of HCV infection compared to mock cells, which could be therapeutically relevant in the design of more specific and effective anti-viral therapies.

cGAS-STING-mediated sensing pathways in DNA and RNA virus infections: crosstalk with other sensing pathways.

Viruses cause a variety of diseases in humans and other organisms. The most important defense mechanism against viral infections is initiated when the viral genome is sensed by host proteins, and this results in interferon production and pro-inflammatory cytokine responses. The sensing of the viral genome or its replication intermediates within host cells is mediated by cytosolic proteins. For example, cGAS and IFI16 recognize non-self DNA, and RIG-I and MDA5 recognize non-self RNA. Once these sensors are activated, they trigger a cascade of reactions activating downstream molecules, which eventually results in the transcriptional activation of type I and III interferons, which play a critical role in suppressing viral propagation, either by directly limiting their replication or by inducing host cells to inhibit viral protein synthesis. The immune response against viruses relies solely upon sensing of viral genomes and their downstream signaling molecules. Although DNA and RNA viruses are sensed by distinct classes of receptor proteins, there is a possibility of overlap between the viral DNA and viral RNA sensing mechanisms. In this review, we focus on various host sensing molecules and discuss the associated signaling pathways that are activated in response to different viral infections. We further highlight the possibility of crosstalk between the cGAS-STING and the RIG-I-MAVS pathways to limit viral infections. This comprehensive review delineates the mechanisms by which different viruses evade host cellular responses to sustain within the host cells.

Hierarchically Structured Porous Piezoelectric Polymer Nanofibers for Energy Harvesting.

Hierarchically porous piezoelectric polymer nanofibers are prepared through precise control over the thermodynamics and kinetics of liquid-liquid phase separation of nonsolvent (water) in poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) solution. Hierarchy is achieved by fabricating fibers with pores only on the surface of the fiber, or pores only inside the fiber with a closed surface, or pores that are homogeneously distributed in both the volume and surface of the nanofiber. For the fabrication of hierarchically porous nanofibers, guidelines are formulated. A detailed experimental and simulation study of the influence of different porosities on the electrical output of piezoelectric nanogenerators is presented. It is shown that bulk porosity significantly increases the power output of the comprising nanogenerator, whereas surface porosity deteriorates electrical performance. Finite element method simulations attribute the better performance to increased volumetric strain in bulk porous nanofibers.

Doping free transfer of graphene using aqueous ammonia flow.

Doping-free transfer of graphene produced by catalytic chemical vapor deposition (CVD) on copper foil, is still a technical challenge since unintentional doping of the transferred graphene layer yields an uncontrolled shift of Dirac point in graphene-based field-effect transistors (FETs). Typically, CVD graphene is released from the growth template by etching of the template, i.e. copper. During the etching process, ions adhere to the graphene layer resulting in unintentional doping. We demonstrate that washing a CVD graphene layer in an aqueous ammonia flow bath after etching copper, removes the majority of the unintentional dopants. FETs fabricated from graphene after washing in DI-water display a large scattering in Dirac bias with lowered mobility. In contrast, FETs from graphene that is washed in ammonia furnish better performance with high geometrically normalized mobility exceeding 2.4 × 104 cm2 V-1 s-1, balanced transport and a Dirac voltage near zero. We attribute the improved FET behavior to effective removal of the ions with a typical density of 4 × 1012 cm-2 from the graphene layer.

Solution-processed transparent ferroelectric nylon thin films.

Ferroelectricity, a bistable ordering of electrical dipoles in a material, is widely used in sensors, actuators, nonlinear optics, and data storage. Traditional ferroelectrics are ceramic based. Ferroelectric polymers are inexpensive lead-free materials that offer unique features such as the freedom of design enabled by chemistry, the facile solution-based low-temperature processing, and mechanical flexibility. Among engineering polymers, odd nylons are ferroelectric. Since the discovery of ferroelectricity in polymers, nearly half a century ago, a solution-processed ferroelectric nylon thin film has not been demonstrated because of the strong tendency of nylon chains to form hydrogen bonds. We show the solution processing of transparent ferroelectric thin film capacitors of odd nylons. The demonstration of ferroelectricity, as well as the way to obtain thin films, makes odd nylons attractive for applications in flexible devices, soft robotics, biomedical devices, and electronic textiles.

One-Dimensional Polarization Dynamics in Ferroelectric Polymers.

Despite the realization of ferroelectricity in the δ-phase of poly(vinyleden difluoride) (PVDF) nearly four decades ago, the dynamics of polarization switching has not been studied yet. Here, we unravel the polarization switching mechanism as a one-dimensional process that is nucleated by a 90° rotation of a CH2-CF2 repeat unit, forming a kink with reversed dipole along the polymer chain. The kink subsequently propagates in time, yielding full polarization reversal along the chain while preserving TGTG' chain conformation. We show that the domain wall mobility in δ-phase PVDF is faster than both conventional ferroelectric ß-phase PVDF and its copolymers with trifluoroethylene, P(VDF-TrFE). The switching time at infinite electric field for δ-phase PVDF is ten times faster and amounts to 500 ps. Fast switching dynamics combined with the low voltage operation and high thermal stability of polarization make δ-PVDF a suitable candidate for microelectronic applications.