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Regulation of SNPH ubiquitination

Schematic model for SNPH regulation of mitochondrial trafficking in tumor cells

Pathway analysis of SNPH-associated proteins

Syntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission, that is dynamics. Expression of ubiquitination-defective SNPH mutant Lys111→Arg or Lys153→Arg increased the speed and distance traveled by mitochondria, repositioned mitochondria to the cortical cytoskeleton, and supported heightened tumor chemotaxis, invasion, and metastasis in vivo. Interference with SNPH ubiquitination activated mitochondrial dynamics, resulting in increased recruitment of the fission regulator dynamin-related protein-1 (Drp1) to mitochondria and Drp1-dependent tumor cell motility. These data uncover nondegradative ubiquitination of SNPH as a key regulator of mitochondrial trafficking and tumor cell motility and invasion. In this way, SNPH may function as a unique, ubiquitination-regulated suppressor of metastasis.Significance: These findings reveal a new mechanism of metastasis suppression by establishing the role of SNPH ubiquitination in inhibiting mitochondrial dynamics, chemotaxis, and metastasis. Cancer Res; 78(15); 4215–28. ©2018 AACR.

Contents of Supplementary Figures ans Table

SNPH ubiquitination in tumor chemotaxis and bioenergetics

Regulation of tumor cell invasion by SNPH ubiquitination outside the MBD

Requirement of Drp1 for mitochondrial trafficking

SNPH ubiquitination regulates tubulin binding

Purpose Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. Methods This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness. Discussion This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy. We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety. Trial Registration ClinicalTrials.gov Identifier: NCT03975179; Clinical Research Information Service Identifier: KCT0004606

A Gram-stain-negative, rod-shaped, and strictly aerobic bacterium designated strain G2-bT was isolated from the marine sediment around Jeju Island, South Korea. Strain G2-bT was found to be catalase- and oxidase-positive, white-pigmented, motile with polar flagellum, and to grow optimally at 25 °C, pH 7.0 in the presence of 4% (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain G2-bT belongs to the genus Salinimonas and was closely related Salinimonas sediminis N102T (96.7% sequence similarity), Salinimonas iocasae KX18D6T (95.4%), Salinimonas lutimaris DPSR-4T (94.7%), and Salinimonas chungwhensis BH030046T (94.6%). Strain G2-bT possessed ubiquinone 8 as the sole respiratory quinone, summed feature 3 and summed feature 8 as the major fatty acids, and phosphatidylethanolamine and phosphatidylglycerol as the major polar lipids. The genome size and G + C content of the strain G2-bT were determined to be 3,765,169 bp, and 49.7%, respectively, as a complete circular genome. Based on the genomic analyses (e.g., average nucleotide identity and digital DNA–DNA hybridization), the strain G2-BT likely represents a new species in the genus Salinimonas, for which we propose to name this novel bacterium Salinimonas marina sp. nov., and the type strain is designated G2-BT (= KCTC 72817T = VTCC 910110T).

The structural and optical properties of InAsxP1-x metamorphic buffers grown by metal–organic chemical vapor deposition on InP (100) substrates have been investigated. High-resolution X-ray reciprocal space mapping around the (115) InP lattice point reveals that the strain relaxations of the InAsxP1-x with x = 0.5, 0.55, and 0.7 are 98%, 92%, and 96%, while the lateral correlation lengths are 17, 62, and 28 nm, respectively. The optical bandgap energy of the InAsP derived from photoreflectance (PR) measurements decreases from 0.819 to 0.621 eV at 300 K when increasing As composition from x = 0.5 to 0.7. The bowing parameter for the optical bandgap of the InAsP is increased with increasing As composition, which is attributable to the increased spontaneous CuPt-type ordering in InAsP. It is found from the excitation power-dependent PR measurement that the InAsxP1-x layers have different degrees of the bandgap redshift due to the reduced thermal conductivity caused by crystal imperfections generated during the strain relaxation process.

Recent research has claimed virulence factors or antimicrobial resistance in commensal or non-pathogenic Neisseria spp. This study aimed to isolate and analyze commensal microorganisms related to the genus Neisseria from the oral cavity of a patient with head and neck cancer. We successfully isolated strain MA1-1 and identified its functional gene contents. Although strain MA1-1 was related to Neisseria flava based on 16S rRNA gene sequence similarity, genomic relatedness analysis revealed that strain MA1-1 was closely related to Neisseria mucosa, reported as a commensal Neisseria species. The strain MA1-1 genome harbored genes for microaerobic respiration and the complete core metabolic pathway with few transporters for nutrients. A number of genes have been associated with virulence factors and resistance to various antibiotics. In addition, the comparative genomic analysis showed that most genes identified in the strain MA1-1 were shared with other Neisseria spp. including two well-known pathogens, Neisseria gonorrhoeae and Neisseria meningitidis. This indicates that the gene content of intra-members of the genus Neisseria has been evolutionarily conserved and is stable, with no gene recombination with other microbes in the host. Finally, this study provides more fundamental interpretations for the complete gene sequence of commensal Neisseria spp. and will contribute to advancing public health knowledge.

Development of efficient surface passivation methods for semiconductor devices is crucial to counter the degradation in their electrical performance owing to scattering or trapping of carriers in the channels induced by molecular adsorption from the ambient environment. However, conventional dielectric deposition involves the formation of additional interfacial defects associated with broken covalent bonds, resulting in accidental electrostatic doping or enhanced hysteretic behavior. In this study, centimeter-scaled van der Waals passivation of transition metal dichalcogenides (TMDCs) is demonstrated by stacking hydrocarbon (HC) dielectrics onto MoSe

We report on the fabrication of wholly polymeric one-dimensional (1-D) photonic crystals (i.e., Bragg reflectors, Bragg mirrors) via solution processing for use in the near (NIR) and the short wave (SWIR) infrared spectrum (1–2 μm) with very high reflectance (R ∼ 90–97%). Facile fabrication of these highly reflective films was enabled by direct access to solution processable, ultrahigh refractive index polymers, termed, Chalcogenide Hybrid Inorganic/Organic Polymers (CHIPs). The high refractive index (n) of CHIPs materials (n = 1.75–2.10) allowed for the production of narrow band IR Bragg reflectors with high refractive index contrast (Δn ∼ 0.5) when fabricated with low n polymers, such as cellulose acetate (n = 1.47). This is the highest refractive index contrast (Δn ∼ 0.5) demonstrated for an all-polymeric Bragg mirror which directly enabled high reflectivity from films with 22 layers or less. Facile access to modular, thin, highly reflective films from inexpensive CHIPs materials offers a new route to ...

We report on the conformal coating of thickness-tunable multilayers directly onto the sulfur (S8) cathodes by the layer-by-layer (LbL) deposition for the significant improvement in the performances of Li–S batteries even without key additives (LiNO3) in the electrolyte. Poly(ethylene oxide) (PEO)/poly(acrylic acid) (PAA) multilayers on a single poly(allylamine hydrochloride) (PAH)/PAA priming bilayer, deposited on the S8 cathodes, effectively protected from the polysulfide leakage, while providing a Li+ ion diffusion channel. As a result, PAH/PAA/(PEO/PAA)3 multilayer-coated cathodes exhibited the highest capacity retention (806 mAh g–1) after 100 cycles at 0.5 C, as well as the high C-rate capability up to 2.0 C. Furthermore, the multilayer coating effectively mitigated the polysulfide shuttle effect in the absent of LiNO3 additives in the electrolyte.

A series of WO3/multiwalled carbon nanotube (MWCNT) nanocomposite sensors was fabricated by bar-coating slurries using different ratios of MWCNTs to WO3 nanoparticles. The morphology, composition, and structure of the fabricated nanocomposites were examined using electron microscopy, X-ray diffraction, ultraviolet and X-ray photoelectron spectroscopy, Raman spectroscopy, and nitrogen adsorption-desorption measurements, with the aim of completely identifying the physical and electronic structures of the nanocomposites. The effects of the different ratios of the nanocomposites on the electrical conductance and NO2 gas sensing properties were examined and compared with the morphological investigation results. The synergetic properties of the nanocomposite sensors were a result of the combined effect of low-doped semiconducting WO3 and metallic MWCNTs. Because nanoscale sensors exhibit a maximal response on the scale of their depletion depth, individual components with conductivities that are either too low or too high cannot meet the condition. Meanwhile, their mixture can establish the required condition for the maximal response which appears as a synergetic effect. Based on this effect, the optimal nanocomposite sensor (0.5 wt% MWCNT) showed a response of ~18 for 5 ppm NO2 at 150 °C with short response/recovery times (~87 s /~300 s). The synergetic effect in nanocomposite sensors cannot be explained by the interfacial Schottky barrier model, which has been used for sensors of agglomerated particles.

We demonstrated the feasibility of using InP (100) substrates, a different indium source, for the synthesis of In2O3 nanowires by the vapor–liquid–solid (VLS) method using a 20-nm-thick Au layer as a catalyst. By varying the thickness of the Au layer and the growth temperature (T), the nanowires showed different morphologies. The nanowires grew along the (100) direction and had perfect crystallinity and lengths up to several hundreds of micrometers. The configured field-effect transistor revealed an n-type behavior with 115 μA of the drain-source current, IDS, under 1.0 V of gate voltage, VDS, at 1.33 × 10−4 kPa of pressure and temperature of 20°C. This result indicates that it is feasible to use different In sources to synthesize In2O3 nanowires by the VLS method for electronic devices.

Ultrathin uracil-complexed CdS nanowires (U-CdS NWs) were synthesized using a facile wet-chemical process and exploited as an effective electron transport layer (ETL) in organic solar cells (OSCs). The U-CdS NW layer acted as a functional interfacial layer between the active organic and inorganic ZnO films; the functional N H and C O groups in uracil passivated the ZnO surface defects and CdS provided a favorable energy band alignment, which facilitated electron transportation. As a result, the power-conversion efficiency (PCE) of the OSC with U-CdS NWs was 3.52% (maximum PCE of 3.7%), which was 22% higher than that of an OSCs with bare ZnO. Moreover, OSCs with U-CdS NWs had two times longer storage lifetimes because of the enhanced interfacial quality and the hydrophobic nature of U-CdS NWs. These results demonstrate the potential of U-CdS NWs for enhancing the efficiency and stability of OSCs and represent an important step toward the commercialization of OSCs.

Viruses promote infection by hijacking the ubiquitin machinery of the host to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defences and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but previously identified substrates of the redirected ligase do not explain these phenotypes. Here, we used a quantitative proteomics approach to identify substrates of E1B55K/E4orf6-mediated ubiquitination that facilitate RNA processing. While all currently known cellular substrates of E1B55K and E4orf6 are degraded by the proteasome, we uncovered RNA-binding proteins as high-confidence substrates that are not decreased in overall abundance. We focused on two RNA-binding proteins, RALY and hnRNP-C, which we confirm are ubiquitinated without degradation. Knockdown of RALY and hnRNP-C increased levels of viral RNA splicing, protein abundance and progeny production during infection with E1B55K-deleted virus. Furthermore, infection with E1B55K-deleted virus resulted in an increased interaction of hnRNP-C with viral RNA and attenuation of viral RNA processing. These data suggest that viral-mediated ubiquitination of RALY and hnRNP-C relieves a restriction on viral RNA processing and reveal an unexpected role for non-degradative ubiquitination in the manipulation of cellular processes during virus infection. Adenovirus produces two early proteins, E1B55K and E4orf6, that become components of the host cell ubiquitin ligase complex comprising elongin-B and C, cullin-5 and RBX1. The authors identified new protein substrates that are ubiquitinated by the E1B55K–E4orf6 complex and find that hnRNP-C and RALY play an inhibitory role on late viral RNA transcripts and that this is counteracted by ubiquitination due to a reduction on the capacity of these proteins to interact with viral RNA.

New high-k gate dielectrics are highly necessary in facilitating the continuous down-scaling of metal–oxide–semiconductor devices to the sub-10 nm range. This study presents ultrathin organic hydrocarbon (HC) films as a novel high-k gate insulator for metal–insulator–semiconductor (MIS) devices. During inductively-coupled plasma chemical vapor deposition with CH4 and H2 gases, the growth temperature greatly affects the structure of the carbon layers and consequently their dielectric characteristics. Specifically, sp2-rich dielectric HC layers are formed below 600 °C, whereas highly-ordered sp2-hybridized graphene is formed at 950 °C. The k value of the resulting HC films increases up to a maximum value of 90 at 350 °C. Moreover, the MIS devices exhibit excellent gate-insulating properties, including almost no hysteresis in the capacitance–voltage curve, low leakage current, and high dielectric strength, which surpass those of existing high-k gate oxides. These results reveal that the organic HC films are a promising next-generation high-k gate dielectric material for sub-10 nm node Si and organic semiconductor technologies.

To promote recovery in psychosis, targeting modifiable factors related to recovery is critical. Using more strict definition of full recovery, we examined predictors for recovery in patients with early stage schizophrenia spectrum disorders (SSD) followed up to 6.5 years. The target subjects were 375 patients with early stage SSD who had been over at least 1-year after registration and evaluated. The criteria for full recovery were having the score of the Positive and Negative Syndrome Scale (PANSS) 8-item ≤ 2 and adequate functional recovery for at least 1-year. We performed univariate Cox and stepwise Cox regression in both total and acute patients. In stepwise Cox regression, several independent predictors for recovery, i.e., negative symptoms of the PANSS, duration of untreated psychosis (DUP) and non-professional job were identified in patients with early stage SSD. In acute patients, other factors such as professional job and subjective well-being under neuroleptics were more important. The present study identified independent predictors for recovery modifiable by various psychosocial intervention and early intervention services. Moreover, it highlights the need of providing different treatment strategies depending on clinical status.

The Schlafen gene family encodes for proteins involved in various biological tasks, including cell proliferation, differentiation, and T cell development. Schlafens were initially discovered in mice, and have been studied in the context of cancer biology, as well as their role in protecting cells during viral infection. This protein family provides antiviral barriers via direct and indirect effects on virus infection. Schlafens can inhibit the replication of viruses with both RNA and DNA genomes. In this review, we summarize the cellular functions and the emerging relationship between Schlafens and innate immunity. We also discuss the functions and distinctions of this emerging family of proteins as host restriction factors against viral infection. Further research into Schlafen protein function will provide insight into their mechanisms that contribute to intrinsic and innate host immunity.

Assembly of infectious influenza A viruses (IAV) is a complex process involving transport from the nucleus to the plasma membrane. Rab11A-containing recycling endosomes have been identified as a platform for intracellular transport of viral RNA (vRNA). Here, using high spatiotemporal resolution light-sheet microscopy (~1.4 volumes/second, 330 nm isotropic resolution), we quantify Rab11A and vRNA movement in live cells during IAV infection and report that IAV infection decreases speed and increases arrest of Rab11A. Unexpectedly, infection with respiratory syncytial virus alters Rab11A motion in a manner opposite to IAV, suggesting that Rab11A is a common host component that is differentially manipulated by respiratory RNA viruses. Using two-color imaging we demonstrate co-transport of Rab11A and IAV vRNA in infected cells and provide direct evidence that vRNA-associated Rab11A have altered transport. The mechanism of altered Rab11A movement is likely related to a decrease in dynein motors bound to Rab11A vesicles during IAV infection., Here, using high spatiotemporal resolution light-sheet and fluorescence microscopy, the authors investigate the role of cytoskeletal components on the intracellular transport of Rab11A and influenza virus (IAV) vRNP), and show a preference for Rab11A movement along microtubules that is not essential for IAV vRNP transport.

Solar absorber Cu2ZnSnS4 (CZTS) films were uniformly deposited on Si/Mo substrates via a facile, cost-effective chemical bath deposition (CBD) by using ribonucleic acid (RNA) nucleobase uracil as the functional building block. The functional sites of uracil, i.e., C O and N H, played a critical role in the complexation of metals via uracil-quartet functional architectures. Stable metal–uracil complexes significantly affected the growth kinetics, enhancing the uniform delivery of multimetal components into films and suppressing the undesirable formation of CuS particles. CZTS films obtained with the addition of 0.05 and 0.5 M uracil exhibited a smooth surface morphology and significantly improved photoconductive performance. The developed RNA-nucleobase-mediated CBD method demonstrates promise as multicomponent compound absorber films, including CZTS and CuInGaSe2, in cost-effective solar cells.

The NFAT family of transcription factors plays an important role in immune system development and function. NFATc1 and NFATc2 are highly expressed in peripheral T cells, and several isoforms are produced via the use of different promoters and polyadenylation sites. The specific isoforms with relatively long C-termini, NFATc1/C and NFATc2/A, have been shown to be modified by SUMO within their specific C-terminal regions, which regulates NFAT protein localization and transactivation activity. Here, we demonstrate that an isoform NFATc1/A, which has a short C-terminus and does not contain the sumoylation sites found in the long isoforms, is also modified by SUMO. NFATc1/A sumoylation increased with low level expression of SUMO E3 ligases, specifically PIAS1, PIAS3, and PIASy, in co-transfected cells. PIAS3 interacted with NFATc1/A and an active site mutant failed to promote NFATc1/A sumoylation, indicating a role for PIAS3 as a SUMO E3 ligase. A lysine residue at 351 within the central regulatory domain was identified as the major SUMO attachment site in both co-transfection and in vitro assays. Sumoylation of NFATc1/A did not affect nuclear translocation upon ionomycin and phorbol 12-myristate 13-acetate treatment. However, although sumoylation of NFATc1/A slightly increased protein stability, it inhibited transactivation activity for reporter genes driven by promoters containing NFAT sites. Our results indicate that the transactivation activity of NFATc1/A is negatively regulated by PIAS protein-mediated sumoylation, and that SUMO is a general regulator of NFAT family members with either long or short C-termini.

Titanium nitride (TiN) is a material of interest for electrodes owing to its high-temperature stability, robustness, low-cost, and suitable electrical properties. Herein, we studied the surface morphology and electrical properties of TiN thin film deposited onto an Si/SiO2 substrate through direct current (DC) sputtering with a high-purity TiN target in an argon-gas environment. The electrical properties and surface morphology of TiN thin film significantly improved with increased source power and decreased working pressure. The improved electrical properties could be attributed to the suppressed secondary phase (Ti2N) formation and the reduced electron scattering on smoother surface. Consequently, high-quality TiN thin film with the lowest resistivity (ρ = 0.1 mΩ·cm) and the smallest surface roughness (RMS roughness, Rq = 0.3 nm) was obtained under the optimized condition. The TiN film was further used as the bottom electrode for a metal–insulator–metal (MIM) capacitor. Results demonstrated that the electrical properties of TiN film were comparable to those of noble-metal thin films. Therefore, the TiN thin film fabricated by DC sputtering method had excellent electrical properties and good Rq, indicating its potential applications in MIM capacitors and Si technology.

The morphology of MoS2 nanostructures was manipulated from thin films to vertically aligned few-layer nanosheets on graphene, in a controllable and practical manner, using metalorganic chemical vapor deposition. The effects of graphene layer and MoS2 morphology on photoelectrochemical (PEC) performance were systematically studied on the basis of electronic structure and transitions, carrier dynamic behavior, and PEC measurements. The heterojunction quality of the graphene/vertical few-layer MoS2 nanosheets was ensured by low-temperature growth at 250−300 °C, resulting in significantly improved charge transfer properties. As a result, the PEC photocurrent density and photoconversion efficiency of the few-layer MoS2 nanosheets significantly increased upon the insertion of a graphene layer. Among the graphene/MoS2 samples, the few-layer MoS2 nanosheet samples exhibited shorter carrier lifetimes and smaller charge transfer resistances than the thin film samples, suggesting that vertically aligned nanosheets provide highly conductive edges as an efficient pathway for photo-generated carriers and have better electronic contact with graphene. In addition, the height of vertical MoS2 nanosheets on graphene should be controlled within the carrier diffusion length (~200 nm) to achieve the optimal PEC performance. These results can be utilized effectively to exploit the full potential of two-dimensional MoS2 for various PEC applications.

Efficient visible-light photocatalysis was realized by exploring self-induced defect states, including the abundant surface states of TiO2-δ nanobelts synthesized through metal–organic chemical vapor deposition (MOCVD). The TiO2-δ nanobelts exhibited two strong defect-induced absorption peaks at 2.91 and 1.92 eV, overlapping with the conduction band states so that photoexcited carriers can contribute effectively for the photocatalysis reaction. To further enhance visible-light photocatalytic activity, carbon atoms, the by-product of the MOCVD reaction, were self-doped at the judiciously determined growth conditions. The resulting visible-light photocatalysis suggests that the large surface area and consequent high concentration of the surface states of the TiO2-δ nanobelts can be effectively utilized in a wide range of photocatalysis applications.

A controllable approach that combines surface plasmon resonance and two-dimensional (2D) graphene/MoS2 heterojunction has not been implemented despite its potential for efficient photoelectrochemical (PEC) water splitting. In this study, plasmonic Ag-decorated 2D MoS2 nanosheets were vertically grown on graphene substrates in a practical large-scale manner through metalorganic chemical vapor deposition of MoS2 and thermal evaporation of Ag. The plasmonic Ag-decorated MoS2 nanosheets on graphene yielded up to 10 times higher photo-to-dark current ratio than MoS2 nanosheets on indium tin oxide. The significantly enhanced PEC activity could be attributed to the synergetic effects of SPR and favorable graphene/2D MoS2 heterojunction. Plasmonic Ag nanoparticles not only increased visible-light and near-infrared absorption of 2D MoS2, but also induced highly amplified local electric field intensity in 2D MoS2. In addition, the vertically aligned 2D MoS2 on graphene acted as a desirable heterostructure for efficient separation and transportation of photo-generated carriers. This study provides a promising path for exploiting the full potential of 2D MoS2 for practical large-scale and efficient PEC water-splitting applications.

Highlights Controllable and large-scale practical growth of plasmonic Ag-decorated vertically aligned 2D MoS2 nanosheets on graphene.Realization of the synergistic effects of surface plasmon resonance and favorable graphene/MoS2 heterojunction to enhance the photoelectrochemical reactivity of 2D MoS2. Electronic supplementary material The online version of this article (10.1007/s40820-020-00512-3) contains supplementary material, which is available to authorized users., A controllable approach that combines surface plasmon resonance and two-dimensional (2D) graphene/MoS2 heterojunction has not been implemented despite its potential for efficient photoelectrochemical (PEC) water splitting. In this study, plasmonic Ag-decorated 2D MoS2 nanosheets were vertically grown on graphene substrates in a practical large-scale manner through metalorganic chemical vapor deposition of MoS2 and thermal evaporation of Ag. The plasmonic Ag-decorated MoS2 nanosheets on graphene yielded up to 10 times higher photo-to-dark current ratio than MoS2 nanosheets on indium tin oxide. The significantly enhanced PEC activity could be attributed to the synergetic effects of SPR and favorable graphene/2D MoS2 heterojunction. Plasmonic Ag nanoparticles not only increased visible-light and near-infrared absorption of 2D MoS2, but also induced highly amplified local electric field intensity in 2D MoS2. In addition, the vertically aligned 2D MoS2 on graphene acted as a desirable heterostructure for efficient separation and transportation of photo-generated carriers. This study provides a promising path for exploiting the full potential of 2D MoS2 for practical large-scale and efficient PEC water-splitting applications. Electronic supplementary material The online version of this article (10.1007/s40820-020-00512-3) contains supplementary material, which is available to authorized users.

Viruses promote infection by hijacking host ubiquitin machinery to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defenses and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but previously identified substrates of the redirected ligase do not explain these phenotypes. Here we used a quantitative proteomics approach to identify substrates of E1B55K/E4orf6-mediated ubiquitination that facilitate RNA processing. While all currently known cellular substrates of E1B55K/E4orf6 are degraded by the proteasome, we uncovered RNA-binding proteins (RBPs) as high-confidence substrates which are not decreased in overall abundance. We focused on two RBPs, RALY and hnRNP-C, which we confirm are ubiquitinated without degradation. Knockdown of RALY and hnRNP-C increased levels of viral RNA splicing, protein abundance, and progeny production during infection with E1B55K-deleted virus. Furthermore, infection with virus deleted for E1B55K resulted in increased interaction of hnRNP-C with viral RNA, and attenuation of viral RNA processing. These data suggest viral-mediated ubiquitination of RALY and hnRNP-C relieves a restriction on viral RNA processing, revealing an unexpected role for non-degradative ubiquitination in manipulation of cellular processes during virus infection.

Vertically-standing, few-layer MoS2 flakes were uniformly and conformally grown on closely-packed TiO2 nanowire substrates using metal-organic chemical vapor deposition. The TiO2/MoS2 heterostructures exhibited remarkably improved photoelectrochemical (PEC) performance and long-term stability owing to enhanced photogenerated electron–hole separation and transfer properties across the heterojunction. Due to the built-in heterojunction potential, the onset potential of TiO2/MoS2 heterostructures was cathodic-shifted to −0.3 V, thereby resulting in maximum PEC reactivity at approximately zero potential. In contrast, MoS2 flakes on fluorine-doped tin oxide substrates exhibited an onset potential of approximately 0.3 V. Furthermore, PEC performance was critically affected by the size of the vertically-standing MoS2 flakes, indicating that controlled conformal growth of MoS2 flakes on appropriate nanostructures is essential to exploit these nanostructures as efficient, non-toxic, inexpensive, and earth-abundant PEC electrodes.

Intrinsic antiviral host factors confer cellular defence by limiting virus replication and are often counteracted by viral countermeasures. We reasoned that host factors that inhibit viral gene expression could be identified by determining proteins bound to viral DNA (vDNA) in the absence of key viral antagonists. Herpes simplex virus 1 (HSV-1) expresses E3 ubiquitin-protein ligase ICP0 (ICP0), which functions as an E3 ubiquitin ligase required to promote infection. Cellular substrates of ICP0 have been discovered as host barriers to infection but the mechanisms for inhibition of viral gene expression are not fully understood. To identify restriction factors antagonized by ICP0, we compared proteomes associated with vDNA during HSV-1 infection with wild-type virus and a mutant lacking functional ICP0 (ΔICP0). We identified the cellular protein Schlafen family member 5 (SLFN5) as an ICP0 target that binds vDNA during HSV-1 ΔICP0 infection. We demonstrated that ICP0 mediates ubiquitination of SLFN5, which leads to its proteasomal degradation. In the absence of ICP0, SLFN5 binds vDNA to repress HSV-1 transcription by limiting accessibility of RNA polymerase II to viral promoters. These results highlight how comparative proteomics of proteins associated with viral genomes can identify host restriction factors and reveal that viral countermeasures can overcome SLFN antiviral activity.