Structural insights into the recognition of telomeric variant repeat TTGGGG by broad-complex, tramtrack and bric-à-brac - zinc finger protein ZBTB10.

Multiple proteins bind to telomeric DNA and are important for the role of telomeres in genome stability. A recent study established a broad-complex, tramtrack and bric-à-brac - zinc finger (BTB-ZF) protein, ZBTB10 (zinc finger and BTB domain-containing protein 10), as a telomeric variant repeat-binding protein at telomeres that use an alternative method for lengthening telomeres). ZBTB10 specifically interacts with the double-stranded telomeric variant repeat sequence TTGGGG by employing its tandem C2H2 zinc fingers (ZF1-2). Here, we solved the crystal structure of human ZBTB10 ZF1-2 in complex with a double-stranded DNA duplex containing the sequence TTGGGG to assess the molecular details of this interaction. Combined with calorimetric analysis, we identified the vital residues in TTGGGG recognition and determined the specific recognition mechanisms that are different from those of TZAP (telomere zinc finger-associated protein), a recently defined telomeric DNA-binding protein. Following these studies, we further identified a single amino-acid mutant (Arg767Gln) of ZBTB10 ZF1-2 that shows a preference for the telomeric DNA repeat TTAGGG sequence. We solved the cocrystal structure, providing a structural basis for telomeric DNA recognition by C2H2 ZF proteins.

Epstein-Barr virus envelope glycoprotein 110 inhibits NF-κB activation by interacting with NF-κB subunit p65.

Epstein-Barr virus (EBV) is a member of the lymphotropic virus family and is highly correlated with some human malignant tumors. It has been reported that envelope glycoprotein 110 (gp110) plays an essential role in viral fusion, DNA replication, and nucleocapsid assembly of EBV. However, it has not been established whether gp110 is involved in regulating the host's innate immunity. In this study, we found that gp110 inhibits tumor necrosis factor α-mediated NF- κB promoter activity and the downstream production of NF- κB-regulated cytokines under physiological conditions. Using dual-luciferase reporter assays, we showed that gp110 might impede the NF-κB promoter activation downstream of NF-κB transactivational subunit p65. Subsequently, we used coimmunoprecipitation assays to demonstrate that gp110 interacts with p65 during EBV lytic infection, and that the C-terminal cytoplasmic region of gp110 is the key interaction domain with p65. Furthermore, we determined that gp110 can bind to the N-terminal Rel homologous and C-terminal domains of p65. Alternatively, gp110 might not disturb the association of p65 with nontransactivational subunit p50, but we showed it restrains activational phosphorylation (at Ser536) and nuclear translocation of p65, which we also found to be executed by the C-terminal cytoplasmic region of gp110. Altogether, these data suggest that the surface protein gp110 may be a vital component for EBV to antagonize the host's innate immune response, which is also helpful for revealing the infectivity and pathogenesis of EBV.

Genome-Wide Identification of the GhANN Gene Family and Functional Validation of GhANN11 and GhANN4 under Abiotic Stress.

Annexins (ANNs) are a structurally conserved protein family present in almost all plants. In the present study, 27 GhANNs were identified in cotton and were unevenly distributed across 14 chromosomes. Transcriptome data and RT-qPCR results revealed that multiple GhANNs respond to at least two abiotic stresses. Similarly, the expression levels of GhANN4 and GhANN11 were significantly upregulated under heat, cold, and drought stress. Using virus-induced gene silencing (VIGS), functional characterization of GhANN4 and GhANN11 revealed that, compared with those of the controls, the leaf wilting of GhANN4-silenced plants was more obvious, and the activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) were lower under NaCl and PEG stress. Moreover, the expression of stress marker genes (GhCBL3, GhDREB2A, GhDREB2C, GhPP2C, GhRD20-2, GhCIPK6, GhNHX1, GhRD20-1, GhSOS1, GhSOS2 and GhSnRK2.6) was significantly downregulated in GhANN4-silenced plants after stress. Under cold stress, the growth of the GHANN11-silenced plants was significantly weaker than that of the control plants, and the activities of POD, SOD, and CAT were also lower. However, compared with those of the control, the elasticity and orthostatic activity of the GhANN11-silenced plants were greater; the POD, SOD, and CAT activities were higher; and the GhDREB2C, GhHSP, and GhSOS2 expression levels were greater under heat stress. These results suggest that different GhANN family members respond differently to different types of abiotic stress.

Frequency modulation of terahertz microcavity via strong coupling with plasmonic resonators.

Tunable terahertz (THz) microcavities are crucial for the compact on-chip THz devices, aiming to future cloud-based computing, and artificial-intelligence technologies. However, the solutions to effectively modulate THz microcavities remain elusive. Strong coupling has been widely demonstrated in many configurations at different ambient conditions to date and may serve as a promising tool to modulate THz microcavities. Here, we schematically design a microcavity-plasmon hybrid system, and propose an effective approach to modulating the resonant frequencies of THz microcavities by the microcavity-resonator strong coupling. In this case, we observed the strongly coupling states, where the resultant two-polariton branches exhibit an anti-crossing splitting in the frequency domain, experimentally exhibiting a ∼6.2% frequency modulation to the microcavity compared to the uncoupled case. This work provides an efficient approach to modulating chip-scale THz microcavities, thereby facilitating the development and application of compact THz integrated devices, further empowering the evolution of future information processing and intelligent computing system.

FOLDABLE CAPSULAR VITREOUS BODY IMPLANTATION FOR COMPLICATED RETINAL DETACHMENT CAUSED BY SEVERE OCULAR TRAUMA.

PURPOSE: To explore the effectiveness, safety and psychological impact of foldable capsular vitreous body (FCVB) implantation for complicated retinal detachment caused by severe ocular trauma. METHODS: This was a prospective, single-arm, surgical interventional case series study. A standard 3-port 23-gauge pars plana vitrectomy was performed, and the FCVB was implanted into the vitreous cavity. Observed indicators, including the best-corrected visual acuity, intraocular pressure (IOP), retinal reattachment, complications, and patient satisfaction, were analyzed to evaluate the study. RESULTS: A total of 28 cases (eyes) were enrolled, with a mean follow-up of 16.93 ± 9.67 months and an average age of 51.11 ± 10.14 years, including 22 men (78.57%). The FCVB was successfully implanted, and the retina was reattached in all cases. The postoperative best-corrected visual acuity improved in 7 cases, and remained unchanged in 21 cases ( P > 0.05). The average IOP was 7.01 ± 2.43 mmHg before surgery and 8.54 ± 2.93 mmHg after surgery ( P < 0.05). Complications such as FCVB displacement, endophthalmitis, secondary glaucoma, silicone oil emulsification, and escape did not occur during the follow-up period. Patients with FCVB implantation are highly satisfied. Most patients feel hope, positive, and optimistic about life. CONCLUSION: Foldable capsular vitreous body implantation for complicated retinal detachment caused by severe ocular trauma is effective and safe, and it allows patients to face life positively and optimistically.

Structural and biochemical insights into the recognition of RNA helicase CGH-1 by CAR-1 in C. elegans.

A protein-RNA complex containing the RNA helicase CGH-1 and a germline specific RNA-binding protein CAR-1 is involved in various aspects of function in C. elegans. However, the structural basis for the assembly of this protein complex remains unclear. Here, we elucidate the molecular basis of the recognition of CGH-1 by CAR-1. Additionally, we found that the ATPase activity of CGH-1 is stimulated by NTL-1a MIF4G domain in vitro. Furthermore, we determined the structures of the two RecA-like domains of CGH-1 by X-ray crystallography at resolutions of 1.85 and 2.40 Å, respectively. Structural and biochemical approaches revealed a bipartite interface between CGH-1 RecA2 and the FDF-TFG motif of CAR-1. NMR and structure-based mutations in CGH-1 RecA2 or CAR-1 attenuated or disrupted CGH-1 binding to CAR-1, assessed by ITC and GST-pulldown in vitro. These findings provide insights into a conserved mechanism in the recognition of CGH-1 by CAR-1. Together, our data provide the missing physical links in understanding the assembly and function of CGH-1 and CAR-1 in C. elegans.

The Effect of Harvesting Adults on the Evolution of Reproduction Age Via Density-Dependent Juvenile Mortality.

In this paper, we used a generic two-stage population model to derive an adaptive dynamical system for the evolution of reproduction age and studied how this evolution is driven by the harvest of adults. We considered the tradeoffs between maturation rate and fecundity, juvenile mortality, and adult mortality. We analyzed the benefit and cost of faster maturation under each tradeoff that drives the evolution. We found that harvesting adults affects the evolution of maturation by affecting the benefit. For the tradeoff between maturation and juvenile mortality, harvesting adults does not affect the benefit and thus, does not affect optimal maturation strategy. For the other two tradeoffs, harvesting adults affects the benefit through the equilibrium adult/juvenile ratio, which is determined by the density dependence of juveniles. Harvesting adults causes a slower maturation only if it significantly reduces this ratio, which can only happen with very strong adult protection to juveniles. Otherwise, harvesting adults always causes a faster maturation.

Role of the Exciton-Polariton in a Continuous-Wave Optically Pumped CsPbBr3 Perovskite Laser.

Lead halide perovskites have emerged as excellent optical gain materials for solution-processable and flexible lasers. Recently, continuous-wave (CW) optically driven lasing was established in perovskite crystals; however, the mechanism of low-threshold operation is still disputed. In this study, CW-pumped lasing from one-dimensional CsPbBr3 nanoribbons (NBs) with a threshold of ∼130 W cm-2 is demonstrated, which can be ascribed to the large refractive index induced by the exciton-polariton (EP) effect. Increasing the temperature reduces the exciton fraction of EPs, which decreases the group and phase refractive indices and inhibits lasing above 100 K. Thermal management, including reducing the NB height to ∼120 ± 60 nm and adopting a high-thermal-conductivity sink, e.g., sapphire, is critical for CW-driven lasing, even at cryogenic temperatures. These results reveal the nature of ultralow-threshold lasing with CsPbBr3 and provide insights into the construction of room-temperature CW and electrically driven perovskite macro/microlasers.

Intracellular distribution of pseudorabies virus UL2 and detection of its nuclear import mechanism.

Pseudorabies virus (PRV) UL2 (pUL2) is a multifunctional protein, which is homologous with herpes simplex virus 1 early protein UL2 (hUL2) and crucial for the viral propagation. Yet, how pUL2 executes its roles in the viral life cycle remain inadequately understood. In order to uncover its effect on the procedure of PRV infection, investigation was performed to examine the subcellular distribution of pUL2 and establish its trafficking mechanism. In the present study, enhanced yellow fluorescent protein or Myc tag fused pUL2 was transiently overexpressed in transfected cells and exhibited an absolutely nuclear accumulation without the existence of other PRV proteins. Additionally, the nuclear trafficking of pUL2 was proved to rely on Ran-, transportin-1, importin ß1, importin α1, α3 and α5. Accordingly, these data will benefit the knowledge of pUL2-mediated biological effects in PRV infection cycle.

Epstein-Barr virus tegument protein BGLF2 inhibits NF-κB activity by preventing p65 Ser536 phosphorylation.

Epstein-Barr virus (EBV), a ubiquitous gammaherpesvirus, can regulate the antiviral response of NF-κB signaling, which is critical for cell survival, growth transformation, and virus latency. Here, we showed that tegument protein BGLF2 could inhibit TNF-α-induced NF-κB activity. BGLF2 was shown to interplay with the NF-κB subunits p65 and p50, and the Rel homology domain of p65 was the pivotal region to interact with BGLF2. Nonetheless, BGLF2 did not influence the development of p65-p50 dimerization. Yet, overexpression of BGLF2 inhibited the phosphorylation of p65 Ser536 (but not Ser276) and blocked the nuclear translocation of p65. In addition, knockdown of BGLF2 during EBV lytic replication elevated NF-κB activity and the phosphorylation of p65 Ser536. Taken together, these results suggest that the inhibition of NF-κB activation may serve as a strategy to escape the host's antiviral innate immunity to EBV during its lytic infection.-Chen, T., Wang, Y., Xu, Z., Zou, X., Wang, P., Ou, X., Li, Y., Peng, T., Chen, D., Li, M., Cai, M. Epstein-Barr virus tegument protein BGLF2 inhibits NF-κB activity by preventing p65 Ser536 phosphorylation.

The influence of awareness on epidemic spreading on random networks.

During an outbreak, the perceived infection risk of an individual affects his/her behavior during an epidemic to lower the risk. We incorporate the awareness of infection risk into the Volz-Miller SIR epidemic model, to study the effect of awareness on disease dynamics. We consider two levels of awareness, the local one represented by the prevalence among the contacts of an individual, and the global one represented by the prevalence in the population. We also consider two possible effects of awareness: reducing infection rate or breaking infectious edges. We use the next generation matrix method to obtain the basic reproduction number of our models, and show that awareness acquired during an epidemic does not affect the basic reproduction number. However, awareness acquired from outbreaks in other regions before the start of the local epidemic reduces the basic reproduction number. Awareness always reduces the final size of an epidemic. Breaking infectious edges causes a larger reduction than reducing the infection rate. If awareness reduces the infection rate, the reduction increases with both local and global awareness. However, if it breaks infectious edges, the reduction may not be monotonic. For the same awareness, the reduction may reach a maximum on some intermediate infection rates. Whether local or global awareness has a larger effect on reducing the final size depends on the network degree distribution and the infection rate.

Identification of the molecular determinants for nuclear import of PRV EP0.

Pseudorabies virus (PRV) early protein EP0 is a homologue of the herpes simplex virus 1 (HSV-1) immediate-early protein ICP0, which is a multifunctional protein and important for HSV-1 infection. However, the definite function of EP0 during PRV infection is not clear. In this study, to determine if EP0 might localize to the nucleus, as it is shown for its homologue in HSV-1, the subcellular localization pattern and molecular determinants for the nuclear import of EP0 were investigated. EP0 was demonstrated to predominantly target the nucleus in both PRV infected- and plasmid-transfected cells. Furthermore, the nuclear import of EP0 was shown to be dependent on the Ran-, importin α1-, α3-, α7-, ß1- and transportin-1-mediated multiple pathways. Taken together, these data will open up new horizons for portraying the biological roles of EP0 in the course of PRV lytic cycle.

Protein glycosylation: a promising way to modify the functional properties and extend the application in food system.

Modification of functional properties by glycosylating with polysaccharides is an effective solution to improve the internal disadvantages of native proteins. Generally, protein glycosylation belongs to the first stage of the Maillard reaction in essence. Dry-heating, wet-heating, and their combination are the major methods for the preparation of protein-polysaccharide conjugates (PPC). Spectrophotometry, spectroscopy, electrophoresis, calorimetry, chromatography, and mass spectrometry are confirmed to be the most effective methods for the identification of PPC. After glycosylation, functionalities of the native protein, including solubility, rheological properties, emulsifying properties, foaming properties, gel property, film-forming properties, thermal stability, antioxidant activity, allergenicity, and antibacterial properties, are improved. The PPC is extensively used as an encapsulation or a delivering material in order to improve the bioaccessibility of bioactive compounds in food system. Some new applications in food processing could be explored using PPC as an ingredient based on the improved functional properties, such as 3-dimensional printing food, gelled food, and colloid food. Furthermore, the model of protein glycosylation and the application of PPC in food processing could be extended to other protein modification to broaden the exploitation of native protein resource for the processing of novel foods.

Characterization of the Nucleocytoplasmic Transport Mechanisms of Epstein-Barr Virus BFLF2.

BACKGROUND/AIMS: Epstein-Barr virus (EBV) BFLF2, the homologue of herpes simplex virus 1 (HSV-1) UL31, is crucial for the efficient viral DNA packaging and primary egress across the nuclear membrane. However, we still do not know its subcellular transport mechanisms. METHODS: Interspecies heterokaryon assays were utilized to detect the nucleocytoplasmic shuttling of BFLF2, and mutation analysis, plasmid transfection and fluorescence microscopy assays were performed to identify the functional nuclear localization sequence (NLS) and nuclear export sequence (NES) of BFLF2 in live cells. Furthermore, the nuclear import and export of BFLF2 were assessed by confocal microscopy, co-immunoprecipitation and immunoblot assays. RESULTS: BFLF2 was confirmed to shuttle between the nucleus and cytoplasm. Two predicted NESs were shown to be nonfunctional, yet we proved that the nuclear export of BFLF2 was mediated through transporter associated with antigen processing (TAP), but not chromosomal region maintenance 1 (CRM1) dependent pathway. Furthermore, one functional NLS, 22RRLMHPHHRNYTASKASAH40, was identified, and the aa22-23, aa22-25, aa28-30 and aa37-40 had an important role in the nuclear localization of BFLF2. Besides, the nuclear import of BFLF2 was demonstrated through Ran-, importin α7-, importin ß1- and transportin-1-dependent mechanism that does not require importin α1, α3 and α5. CONCLUSION: These works are of significance for the further study of the functions of BFLF2 during EBV infection, as well as for further insights into the design of new antiviral drug target and vaccine development against EBV.

A Two-Dimensional Ruddlesden-Popper Perovskite Nanowire Laser Array based on Ultrafast Light-Harvesting Quantum Wells.

Miniaturized nanowire nanolasers of 3D perovskites feature a high gain coefficient; however, room-temperature optical gain and nanowire lasers from 2D layered perovskites have not been reported to date. A biomimetic approach is presented to construct an artificial ligh-harvesting system in mixed multiple quantum wells (QWs) of 2D-RPPs of (BA)2 (FA)n-1 Pbn Br3n+1 , achieving room-temperature ASE and nanowire (NW) lasing. Owing to the improvement of flexible and deformable characteristics provided by organic BA cation layers, high-density large-area NW laser arrays were fabricated with high photostability. Well-controlled dimensions and uniform geometries enabled 2D-RPPs NWs functioning as high-quality Fabry-Perot (FP) lasers with almost identical optical modes, high quality (Q) factor (ca. 1800), and similarly low lasing thresholds.

Characterization of the subcellular localization and nuclear import molecular mechanisms of herpes simplex virus 1 UL2.

As a crucial protein, the herpes simplex virus 1 (HSV-1) UL2 protein has been shown to take part in various stages of viral infection, nonetheless, its exact subcellular localization and transport molecular determinants are not well known thus far. In the present study, by using live cells fluorescent microscopy assay, UL2 tagged with enhanced yellow fluorescent protein was transiently expressed in live cells and showed a completely nuclear accumulation without the presence of other HSV-1 proteins. Moreover, the nuclear transport of UL2 was characterized to be assisted by multiple transport pathways through Ran-, importin α1-, α5-, α7-, ß1- and transportin-1 cellular transport receptors. Consequently, these results will improve understanding of UL2-mediated biological functions in HSV-1 infection cycles.

Characterization of the nuclear import mechanisms of HSV-1 UL31.

As an important protein, UL31 has been demonstrated to play multiple roles in herpes simplex virus 1 (HSV-1) replication. Previous studies showed that UL31 predominantly locates in the nucleus in chemical fixed cells and live cells, however, the determining mechanisms for its nuclear translocation is not clear. In the present study, by utilizing live cells fluorescent microscopy and co-immunoprecipitation assays, the nuclear import of UL31 was characterized to be dependent on Ran-, importin α1- and transportin-1-mediated pathway. Therefore, these results will promote the understanding of UL31-mediated biological functions in HSV-1 infection cycle.

Characterization of the nuclear import signal of herpes simplex virus 1 UL31.

The herpes simplex virus 1 (HSV-1) UL31 protein is a multifunctional nucleoprotein that is important for viral infection; however, little is known concerning its subcellular localization signal. Here, by transfection with a series of HSV-1 UL31 deletion mutants fused to enhanced yellow fluorescent protein (EYFP), a bipartite nuclear localization signal (NLS) was identified and mapped to amino acids (aa) 1 to 27 (MYDTDPHRRGSRPGPYHGKERRRSRSS). Additionally, fluorescence results showed that the predicted nuclear export signal (NES) might be nonfunctional, and the functional NES of UL31 might require a specific conformation. Taken together, these results would provide significant information for the study of the biological function of UL31 during HSV-1 infection.

Herpes simplex virus 1 counteracts viperin via its virion host shutoff protein UL41.

The interferon (IFN)-inducible viperin protein restricts a broad range of viruses. However, whether viperin plays a role during herpes simplex virus 1 (HSV-1) infection is poorly understood. In the present study, it was shown for the first time that wild-type (WT) HSV-1 infection couldn't induce viperin production, and ectopically expressed viperin inhibited the replication of UL41-null HSV-1 but not WT viruses. The underlying molecular mechanism is that UL41 counteracts viperin's antiviral activity by reducing its mRNA accumulation.

Identification of molecular determinants for the nuclear import of pseudorabies virus UL31.

Herpes simplex virus 1 (HSV-1) UL31 is a multifunctional protein and important for HSV-1 infection. Pseudorabies virus (PRV) UL31 is a late protein homologous to HSV-1 UL31. Previous studies showed that PRV UL31 is predominantly localized to nucleus, however, the molecular determinants for its nuclear import were unclear to date. Here, by utilizing live cells fluorescent microscopy, UL31 fused with enhanced yellow fluorescent protein was transiently expressed in live cells and confirmed to exclusively target to the nucleus in the absence of other viral proteins. Furthermore, the nuclear import of UL31 was found to be dependent on the Ran-, importin α1-, α3-, α5-, α7-, ß1-and transportin-1-mediated pathway. Therefore, these results would open up new avenues for depicting the biological functions of UL31 during PRV infection.